Clinical Endocrinology News

After her emergency medicine group was acquired by a staffing firm backed by a large private equity (PE) firm, Michelle Wiener, MD, said the workflow changes came swiftly.

“Our staffing has been greatly reduced,” the Detroit physician said. “At this point, we have no say in anything. We have no say in the scheduling. We aren’t allowed to see what is billed under our name. The morale has really gone down.”

Dr. Wiener, who practices at Ascension St. John Hospital, said she and fellow physicians have repeatedly brought their concerns to TeamHealth, which in 2015 took over St. John Emergency Services PC. TeamHealth is owned by PE giant Blackstone.

“It’s very frustrating,” Dr. Wiener said. “We’re taking it from all sides.”

Blackstone and Ascension St. John did not respond to this news organization’s request for comment.

TeamHealth would not respond directly to questions about the Ascension St. John Hospital physicians or their concerns.

Spokesman Josh Hopson provided only a general statement: “TeamHealth is committed to making sure that clinicians have the resources and support needed to provide first-class care to patients, particularly with regard to staffing and compensation. TeamHealth has and will always put patient care first, and that is not impacted by its ownership model.”

Acquisitions of medical practices and hospitals by PE firms are rapidly growing, with more than 1,400 PE deals in health care in 2021 totaling upwards of $208 billion, according to PitchBook Data Inc., a Seattle-based firm that tracks mergers and acquisitions.

Some physicians praise the partnerships as an opportunity to improve technology and efficiency, whereas others decry them as raising patient costs and lowering the quality of care. A recent UC Berkeley study found that PE ownership of medical practices was linked to consumer price increases for 8 of 10 specialties, most notably oncology and gastroenterology.
 

What should you expect after PE acquisition?

Since his practice partnered with a PE firm in 2020, Milwaukee-based otolaryngologist Madan Kandula, MD, said he has found the changes positive. The practice has grown and improved operations in finance, accounting, compliance, and information technology, said Dr. Kandula, founder and CEO of Advent, an ENT practice with 15 clinics in four Midwestern states.

Dr. Kandula said his group already had a sound business practice, and that the goal of partnering with a PE firm wasn’t to change day-to-day operations but to propel the organization forward.

“From patient load to visit time to how we staff our clinics, there has been no change,” he said. “My private equity firm does not, [and] cannot, impose their will on our clinical decisions.”

Experts say the impact of PE acquisitions on individual physicians often depends on where a doctor ranks in the organization, what stage they are in their career, and how much control they had over the deal.

“It’s the older physicians who are usually selling the practice and getting the big payout,” said Anjali Dooley, a St. Louis–based health law attorney who counsels physicians about PE deals. “The younger doctors are usually not part of the deal, as they may still be employees. They don’t have any negotiating power. Hopefully, there is some transparency, but sometimes there is not, and they are blindsided by the deal.”

When it comes to workload, most PE-owned groups are put on a production-based model, such as a wRVU-based model, said Roger Strode, a Chicago-based health law attorney who focuses on health care mergers and acquisitions. Most already operate under such a model, but there might be some changes after a buyout.

Staffing may also change, added Ms. Dooley. The PE firms may want to add partners or companies already in their portfolios to create efficiencies, causing training or workflow changes.

In a hospital buyout, changes may depend on whether a department is a significant revenue generator for the hospital, Ms. Dooley noted.

PE firms frequently favor higher revenue–generating specialties, such as neurosurgery, cardiology, orthopedics, gastroenterology, and plastic surgery. They closely scrutinize departments said that make less money, such as the emergency department or primary care, Ms. Dooley said. Physicians or teams that don’t fit the firm’s cost-efficiency plans may be terminated or replaced.

On the other hand, Mr. Strode said physicians may see improved electronic health records and collections.

“Some of your overall overhead costs may be reduced, because they’re better at it,” Mr. Strode said. “When you’ve got more scale, the cost per patient, the cost per hour, the cost per procedure, goes down, and the cost that’s applied against your production will go down. As [practices grow], they have more bargaining power with payers and you can potentially get better rates. At least, that’s the promise.”

Analysts note that PE health care acquisitions show no signs of slowing and that it pays for physicians to know what to expect and how to cope if their practice or hospital is acquired. Whether physicians have some control over a buyout or are blindsided by the transition, it’s critical to know what to consider, how workloads might change, and your options for settling in or settling up.

The PE industry has about $2 trillion lined up for potential investments in 2023, said Ms. Dooley.

“PE firms are looking at health care to expend some of this dry powder,” Ms. Dooley continued. “If done correctly, PE firms that are aware of health care regulations, compliance, and patient care issues can ... remove redundant services and improve ... efficiencies, but the bad is when that doesn’t happen, and the quality of care goes down or there are patient safety risks.”
 

How to prepare for and cope with PE partnerships

If your practice is considering a PE partnership, it’s important to explore the terms and conditions and carefully weigh the pros and cons, said Gary Herschman, a Newark, N.J.–based attorney who advises PE-owned physician groups.

“My recommendation is that physicians at a minimum conduct due diligence on all potential strategic options for their groups, and then make an informed decision regarding whether a partnership transaction is right for their group, as it’s not right for every group,” he said.

When Texas cardiologist Rick Snyder, MD, was considering PE partnerships, he spoke with physicians who made similar deals to determine whether they were satisfied years later, he said. In April, Snyder’s practice, HeartPlace, the largest physician-owned cardiology practice in Texas, was acquired by US Heart & Vascular, a practice management platform backed by PE firm Ares Management.

“I called every group that I knew that had done private equity for any meaningful amount of time,” Dr. Snyder said. “For the first year or two, everybody is in the honeymoon period. If the model is going to succeed or break down, it’s not going to be in the first year or two. So I wanted to talk to groups that had done this for a longer amount of time and find out what their pitfalls were. What would they have done differently? Has it been a productive relationship? Did they grow?”

Dr. Snyder, president of the Texas Medical Association, said his practice met with seven or eight firms before choosing one that best met their needs. His group wanted a platform that preserved their clinical autonomy, governance, and culture, he said. They also wanted to ensure they were not entering into a “buy and flip” scenario, but rather a “buy and build” plan.

“Thus, financial capital was not sufficient, they also had to have intellectual capital and relationship capital on their bench,” he said. “When we found the partner that embraced all of these factors as well as a history of buying and long-term building, we pulled the trigger and partnered with Ares and US Heart & Vascular Management. The partner we chose did not offer us the most money. We put a premium on these other criteria.”

“I always tell docs, know the culture of your group and your vision,” he said. “Before you go down that route, ask yourself what you want to accomplish and if it makes sense having a private equity partner to accomplish that vision with.”

For younger physicians or those with little control over buyouts, experts recommend they review their contracts and consider consulting with an attorney to better understand how the deal may affect their earnings and career prospects.

Those who have a much longer career runway need to weigh whether they want to work for a PE-linked practice, Mr. Strode said. For some, it’s time to check when their noncompete agreements end and find a position elsewhere.

Also, physicians should know their rights and the laws in their states regarding the corporate practice of medicine. Statutes vary by state, and knowing the provisions in your state helps doctors recognize their legal rights, learn possible exceptions to the requirements, and know the penalties for violations.

In Michigan, a group of physicians and other health professionals at Ascension St. John has voted to unionize. Doctors hope that the union, which includes advanced practice clinicians, nurse practitioners, and physician assistants, will help improve patient care and protect working conditions for staff, Dr. Wiener said.

She advises physicians who are unhappy after acquisitions to speak up and stick together.

“That’s the biggest thing I think physicians should start doing,” she said. “Support each other and stand up. You are stronger together.”
 

Why is PE so attracted to health care?

PE firms typically buy practices or hospitals, work to make the entities more profitable, and then sell them, with the goal of doubling or tripling their investment over a short period. In general, PE firms aim for annual returns exceeding 20% after 3-7 years.

These firms know that health care is relatively recession-proof, that providers have third-party payers, and that the industry is fragmented and requires more efficiency, Ms. Dooley said.

When PE practice acquisitions started gaining momentum about 12 years ago, traditional hospital-based specialties such as anesthesiology and radiology were prime targets, said Mr. Strode.

At the same time, increasing challenges in private practice, such as declining compensation from payers, pressure to participate in value-based care programs, and rising regional competitors have fueled more physician groups to partner with PE firms, Mr. Herschman noted.

Physicians who partner with PE firms often benefit by having new access to capital to grow their practices, cost savings through group purchasing, and the ability to compete with larger health groups, Mr. Herschman said.

Questions remain, however, about how PE involvement affects health care use and spending. An April 2023 JAMA Viewpoint article called out the lack of oversight and regulation in the health care/PE space, suggesting that a stronger framework for regulation and transparency is needed.

A 2022 study in JAMA Health Forum that examined changes in prices and utilization associated with the PE acquisitions of 578 dermatology, gastroenterology, and ophthalmology physician practices from 2016 to 2020 found that prices increased by an average of 11%, and volume rose by 16%, after acquisition.

“We found that acquisitions were associated with increases in health care spending and utilization, as well as some other patterns of care like potential upcoding,” said Jane M. Zhu, MD, an author of the study and assistant professor at Oregon Health & Science University in Portland.

Another recent study that Dr. Zhu coauthored, published in Health Affairs, found that physician practices acquired by PE firms experience greater staff turnover and rely more heavily on advanced practice professionals than doctors.

“To the extent that that turnover indicates physicians are dissatisfied after private equity comes in, that’s really important to investigate further,” Dr. Zhu said.

PE firms owned 4% of U.S. hospitals in 2021 and 11% of nursing homes, according to a Medicare Payment Advisory Commission (MedPAC) report. The report does not include 2021 data on medical practices but notes that from 2013 to 2016, PE firms acquired at least 2% of physician practices. Estimates of PE deals are probably lower than actual numbers because of the lack of comprehensive information sources, according to the MedPAC report.

A version of this article appeared on Medscape.com.

After her emergency medicine group was acquired by a staffing firm backed by a large private equity (PE) firm, Michelle Wiener, MD, said the workflow changes came swiftly.

“Our staffing has been greatly reduced,” the Detroit physician said. “At this point, we have no say in anything. We have no say in the scheduling. We aren’t allowed to see what is billed under our name. The morale has really gone down.”

Dr. Wiener, who practices at Ascension St. John Hospital, said she and fellow physicians have repeatedly brought their concerns to TeamHealth, which in 2015 took over St. John Emergency Services PC. TeamHealth is owned by PE giant Blackstone.

“It’s very frustrating,” Dr. Wiener said. “We’re taking it from all sides.”

Blackstone and Ascension St. John did not respond to this news organization’s request for comment.

TeamHealth would not respond directly to questions about the Ascension St. John Hospital physicians or their concerns.

Spokesman Josh Hopson provided only a general statement: “TeamHealth is committed to making sure that clinicians have the resources and support needed to provide first-class care to patients, particularly with regard to staffing and compensation. TeamHealth has and will always put patient care first, and that is not impacted by its ownership model.”

Acquisitions of medical practices and hospitals by PE firms are rapidly growing, with more than 1,400 PE deals in health care in 2021 totaling upwards of $208 billion, according to PitchBook Data Inc., a Seattle-based firm that tracks mergers and acquisitions.

Some physicians praise the partnerships as an opportunity to improve technology and efficiency, whereas others decry them as raising patient costs and lowering the quality of care. A recent UC Berkeley study found that PE ownership of medical practices was linked to consumer price increases for 8 of 10 specialties, most notably oncology and gastroenterology.
 

What should you expect after PE acquisition?

Since his practice partnered with a PE firm in 2020, Milwaukee-based otolaryngologist Madan Kandula, MD, said he has found the changes positive. The practice has grown and improved operations in finance, accounting, compliance, and information technology, said Dr. Kandula, founder and CEO of Advent, an ENT practice with 15 clinics in four Midwestern states.

Dr. Kandula said his group already had a sound business practice, and that the goal of partnering with a PE firm wasn’t to change day-to-day operations but to propel the organization forward.

“From patient load to visit time to how we staff our clinics, there has been no change,” he said. “My private equity firm does not, [and] cannot, impose their will on our clinical decisions.”

Experts say the impact of PE acquisitions on individual physicians often depends on where a doctor ranks in the organization, what stage they are in their career, and how much control they had over the deal.

“It’s the older physicians who are usually selling the practice and getting the big payout,” said Anjali Dooley, a St. Louis–based health law attorney who counsels physicians about PE deals. “The younger doctors are usually not part of the deal, as they may still be employees. They don’t have any negotiating power. Hopefully, there is some transparency, but sometimes there is not, and they are blindsided by the deal.”

When it comes to workload, most PE-owned groups are put on a production-based model, such as a wRVU-based model, said Roger Strode, a Chicago-based health law attorney who focuses on health care mergers and acquisitions. Most already operate under such a model, but there might be some changes after a buyout.

Staffing may also change, added Ms. Dooley. The PE firms may want to add partners or companies already in their portfolios to create efficiencies, causing training or workflow changes.

In a hospital buyout, changes may depend on whether a department is a significant revenue generator for the hospital, Ms. Dooley noted.

PE firms frequently favor higher revenue–generating specialties, such as neurosurgery, cardiology, orthopedics, gastroenterology, and plastic surgery. They closely scrutinize departments said that make less money, such as the emergency department or primary care, Ms. Dooley said. Physicians or teams that don’t fit the firm’s cost-efficiency plans may be terminated or replaced.

On the other hand, Mr. Strode said physicians may see improved electronic health records and collections.

“Some of your overall overhead costs may be reduced, because they’re better at it,” Mr. Strode said. “When you’ve got more scale, the cost per patient, the cost per hour, the cost per procedure, goes down, and the cost that’s applied against your production will go down. As [practices grow], they have more bargaining power with payers and you can potentially get better rates. At least, that’s the promise.”

Analysts note that PE health care acquisitions show no signs of slowing and that it pays for physicians to know what to expect and how to cope if their practice or hospital is acquired. Whether physicians have some control over a buyout or are blindsided by the transition, it’s critical to know what to consider, how workloads might change, and your options for settling in or settling up.

The PE industry has about $2 trillion lined up for potential investments in 2023, said Ms. Dooley.

“PE firms are looking at health care to expend some of this dry powder,” Ms. Dooley continued. “If done correctly, PE firms that are aware of health care regulations, compliance, and patient care issues can ... remove redundant services and improve ... efficiencies, but the bad is when that doesn’t happen, and the quality of care goes down or there are patient safety risks.”
 

How to prepare for and cope with PE partnerships

If your practice is considering a PE partnership, it’s important to explore the terms and conditions and carefully weigh the pros and cons, said Gary Herschman, a Newark, N.J.–based attorney who advises PE-owned physician groups.

“My recommendation is that physicians at a minimum conduct due diligence on all potential strategic options for their groups, and then make an informed decision regarding whether a partnership transaction is right for their group, as it’s not right for every group,” he said.

When Texas cardiologist Rick Snyder, MD, was considering PE partnerships, he spoke with physicians who made similar deals to determine whether they were satisfied years later, he said. In April, Snyder’s practice, HeartPlace, the largest physician-owned cardiology practice in Texas, was acquired by US Heart & Vascular, a practice management platform backed by PE firm Ares Management.

“I called every group that I knew that had done private equity for any meaningful amount of time,” Dr. Snyder said. “For the first year or two, everybody is in the honeymoon period. If the model is going to succeed or break down, it’s not going to be in the first year or two. So I wanted to talk to groups that had done this for a longer amount of time and find out what their pitfalls were. What would they have done differently? Has it been a productive relationship? Did they grow?”

Dr. Snyder, president of the Texas Medical Association, said his practice met with seven or eight firms before choosing one that best met their needs. His group wanted a platform that preserved their clinical autonomy, governance, and culture, he said. They also wanted to ensure they were not entering into a “buy and flip” scenario, but rather a “buy and build” plan.

“Thus, financial capital was not sufficient, they also had to have intellectual capital and relationship capital on their bench,” he said. “When we found the partner that embraced all of these factors as well as a history of buying and long-term building, we pulled the trigger and partnered with Ares and US Heart & Vascular Management. The partner we chose did not offer us the most money. We put a premium on these other criteria.”

“I always tell docs, know the culture of your group and your vision,” he said. “Before you go down that route, ask yourself what you want to accomplish and if it makes sense having a private equity partner to accomplish that vision with.”

For younger physicians or those with little control over buyouts, experts recommend they review their contracts and consider consulting with an attorney to better understand how the deal may affect their earnings and career prospects.

Those who have a much longer career runway need to weigh whether they want to work for a PE-linked practice, Mr. Strode said. For some, it’s time to check when their noncompete agreements end and find a position elsewhere.

Also, physicians should know their rights and the laws in their states regarding the corporate practice of medicine. Statutes vary by state, and knowing the provisions in your state helps doctors recognize their legal rights, learn possible exceptions to the requirements, and know the penalties for violations.

In Michigan, a group of physicians and other health professionals at Ascension St. John has voted to unionize. Doctors hope that the union, which includes advanced practice clinicians, nurse practitioners, and physician assistants, will help improve patient care and protect working conditions for staff, Dr. Wiener said.

She advises physicians who are unhappy after acquisitions to speak up and stick together.

“That’s the biggest thing I think physicians should start doing,” she said. “Support each other and stand up. You are stronger together.”
 

Why is PE so attracted to health care?

PE firms typically buy practices or hospitals, work to make the entities more profitable, and then sell them, with the goal of doubling or tripling their investment over a short period. In general, PE firms aim for annual returns exceeding 20% after 3-7 years.

These firms know that health care is relatively recession-proof, that providers have third-party payers, and that the industry is fragmented and requires more efficiency, Ms. Dooley said.

When PE practice acquisitions started gaining momentum about 12 years ago, traditional hospital-based specialties such as anesthesiology and radiology were prime targets, said Mr. Strode.

At the same time, increasing challenges in private practice, such as declining compensation from payers, pressure to participate in value-based care programs, and rising regional competitors have fueled more physician groups to partner with PE firms, Mr. Herschman noted.

Physicians who partner with PE firms often benefit by having new access to capital to grow their practices, cost savings through group purchasing, and the ability to compete with larger health groups, Mr. Herschman said.

Questions remain, however, about how PE involvement affects health care use and spending. An April 2023 JAMA Viewpoint article called out the lack of oversight and regulation in the health care/PE space, suggesting that a stronger framework for regulation and transparency is needed.

A 2022 study in JAMA Health Forum that examined changes in prices and utilization associated with the PE acquisitions of 578 dermatology, gastroenterology, and ophthalmology physician practices from 2016 to 2020 found that prices increased by an average of 11%, and volume rose by 16%, after acquisition.

“We found that acquisitions were associated with increases in health care spending and utilization, as well as some other patterns of care like potential upcoding,” said Jane M. Zhu, MD, an author of the study and assistant professor at Oregon Health & Science University in Portland.

Another recent study that Dr. Zhu coauthored, published in Health Affairs, found that physician practices acquired by PE firms experience greater staff turnover and rely more heavily on advanced practice professionals than doctors.

“To the extent that that turnover indicates physicians are dissatisfied after private equity comes in, that’s really important to investigate further,” Dr. Zhu said.

PE firms owned 4% of U.S. hospitals in 2021 and 11% of nursing homes, according to a Medicare Payment Advisory Commission (MedPAC) report. The report does not include 2021 data on medical practices but notes that from 2013 to 2016, PE firms acquired at least 2% of physician practices. Estimates of PE deals are probably lower than actual numbers because of the lack of comprehensive information sources, according to the MedPAC report.

A version of this article appeared on Medscape.com.

After her emergency medicine group was acquired by a staffing firm backed by a large private equity (PE) firm, Michelle Wiener, MD, said the workflow changes came swiftly.

“Our staffing has been greatly reduced,” the Detroit physician said. “At this point, we have no say in anything. We have no say in the scheduling. We aren’t allowed to see what is billed under our name. The morale has really gone down.”

Dr. Wiener, who practices at Ascension St. John Hospital, said she and fellow physicians have repeatedly brought their concerns to TeamHealth, which in 2015 took over St. John Emergency Services PC. TeamHealth is owned by PE giant Blackstone.

“It’s very frustrating,” Dr. Wiener said. “We’re taking it from all sides.”

Blackstone and Ascension St. John did not respond to this news organization’s request for comment.

TeamHealth would not respond directly to questions about the Ascension St. John Hospital physicians or their concerns.

Spokesman Josh Hopson provided only a general statement: “TeamHealth is committed to making sure that clinicians have the resources and support needed to provide first-class care to patients, particularly with regard to staffing and compensation. TeamHealth has and will always put patient care first, and that is not impacted by its ownership model.”

Acquisitions of medical practices and hospitals by PE firms are rapidly growing, with more than 1,400 PE deals in health care in 2021 totaling upwards of $208 billion, according to PitchBook Data Inc., a Seattle-based firm that tracks mergers and acquisitions.

Some physicians praise the partnerships as an opportunity to improve technology and efficiency, whereas others decry them as raising patient costs and lowering the quality of care. A recent UC Berkeley study found that PE ownership of medical practices was linked to consumer price increases for 8 of 10 specialties, most notably oncology and gastroenterology.
 

What should you expect after PE acquisition?

Since his practice partnered with a PE firm in 2020, Milwaukee-based otolaryngologist Madan Kandula, MD, said he has found the changes positive. The practice has grown and improved operations in finance, accounting, compliance, and information technology, said Dr. Kandula, founder and CEO of Advent, an ENT practice with 15 clinics in four Midwestern states.

Dr. Kandula said his group already had a sound business practice, and that the goal of partnering with a PE firm wasn’t to change day-to-day operations but to propel the organization forward.

“From patient load to visit time to how we staff our clinics, there has been no change,” he said. “My private equity firm does not, [and] cannot, impose their will on our clinical decisions.”

Experts say the impact of PE acquisitions on individual physicians often depends on where a doctor ranks in the organization, what stage they are in their career, and how much control they had over the deal.

“It’s the older physicians who are usually selling the practice and getting the big payout,” said Anjali Dooley, a St. Louis–based health law attorney who counsels physicians about PE deals. “The younger doctors are usually not part of the deal, as they may still be employees. They don’t have any negotiating power. Hopefully, there is some transparency, but sometimes there is not, and they are blindsided by the deal.”

When it comes to workload, most PE-owned groups are put on a production-based model, such as a wRVU-based model, said Roger Strode, a Chicago-based health law attorney who focuses on health care mergers and acquisitions. Most already operate under such a model, but there might be some changes after a buyout.

Staffing may also change, added Ms. Dooley. The PE firms may want to add partners or companies already in their portfolios to create efficiencies, causing training or workflow changes.

In a hospital buyout, changes may depend on whether a department is a significant revenue generator for the hospital, Ms. Dooley noted.

PE firms frequently favor higher revenue–generating specialties, such as neurosurgery, cardiology, orthopedics, gastroenterology, and plastic surgery. They closely scrutinize departments said that make less money, such as the emergency department or primary care, Ms. Dooley said. Physicians or teams that don’t fit the firm’s cost-efficiency plans may be terminated or replaced.

On the other hand, Mr. Strode said physicians may see improved electronic health records and collections.

“Some of your overall overhead costs may be reduced, because they’re better at it,” Mr. Strode said. “When you’ve got more scale, the cost per patient, the cost per hour, the cost per procedure, goes down, and the cost that’s applied against your production will go down. As [practices grow], they have more bargaining power with payers and you can potentially get better rates. At least, that’s the promise.”

Analysts note that PE health care acquisitions show no signs of slowing and that it pays for physicians to know what to expect and how to cope if their practice or hospital is acquired. Whether physicians have some control over a buyout or are blindsided by the transition, it’s critical to know what to consider, how workloads might change, and your options for settling in or settling up.

The PE industry has about $2 trillion lined up for potential investments in 2023, said Ms. Dooley.

“PE firms are looking at health care to expend some of this dry powder,” Ms. Dooley continued. “If done correctly, PE firms that are aware of health care regulations, compliance, and patient care issues can ... remove redundant services and improve ... efficiencies, but the bad is when that doesn’t happen, and the quality of care goes down or there are patient safety risks.”
 

How to prepare for and cope with PE partnerships

If your practice is considering a PE partnership, it’s important to explore the terms and conditions and carefully weigh the pros and cons, said Gary Herschman, a Newark, N.J.–based attorney who advises PE-owned physician groups.

“My recommendation is that physicians at a minimum conduct due diligence on all potential strategic options for their groups, and then make an informed decision regarding whether a partnership transaction is right for their group, as it’s not right for every group,” he said.

When Texas cardiologist Rick Snyder, MD, was considering PE partnerships, he spoke with physicians who made similar deals to determine whether they were satisfied years later, he said. In April, Snyder’s practice, HeartPlace, the largest physician-owned cardiology practice in Texas, was acquired by US Heart & Vascular, a practice management platform backed by PE firm Ares Management.

“I called every group that I knew that had done private equity for any meaningful amount of time,” Dr. Snyder said. “For the first year or two, everybody is in the honeymoon period. If the model is going to succeed or break down, it’s not going to be in the first year or two. So I wanted to talk to groups that had done this for a longer amount of time and find out what their pitfalls were. What would they have done differently? Has it been a productive relationship? Did they grow?”

Dr. Snyder, president of the Texas Medical Association, said his practice met with seven or eight firms before choosing one that best met their needs. His group wanted a platform that preserved their clinical autonomy, governance, and culture, he said. They also wanted to ensure they were not entering into a “buy and flip” scenario, but rather a “buy and build” plan.

“Thus, financial capital was not sufficient, they also had to have intellectual capital and relationship capital on their bench,” he said. “When we found the partner that embraced all of these factors as well as a history of buying and long-term building, we pulled the trigger and partnered with Ares and US Heart & Vascular Management. The partner we chose did not offer us the most money. We put a premium on these other criteria.”

“I always tell docs, know the culture of your group and your vision,” he said. “Before you go down that route, ask yourself what you want to accomplish and if it makes sense having a private equity partner to accomplish that vision with.”

For younger physicians or those with little control over buyouts, experts recommend they review their contracts and consider consulting with an attorney to better understand how the deal may affect their earnings and career prospects.

Those who have a much longer career runway need to weigh whether they want to work for a PE-linked practice, Mr. Strode said. For some, it’s time to check when their noncompete agreements end and find a position elsewhere.

Also, physicians should know their rights and the laws in their states regarding the corporate practice of medicine. Statutes vary by state, and knowing the provisions in your state helps doctors recognize their legal rights, learn possible exceptions to the requirements, and know the penalties for violations.

In Michigan, a group of physicians and other health professionals at Ascension St. John has voted to unionize. Doctors hope that the union, which includes advanced practice clinicians, nurse practitioners, and physician assistants, will help improve patient care and protect working conditions for staff, Dr. Wiener said.

She advises physicians who are unhappy after acquisitions to speak up and stick together.

“That’s the biggest thing I think physicians should start doing,” she said. “Support each other and stand up. You are stronger together.”
 

Why is PE so attracted to health care?

PE firms typically buy practices or hospitals, work to make the entities more profitable, and then sell them, with the goal of doubling or tripling their investment over a short period. In general, PE firms aim for annual returns exceeding 20% after 3-7 years.

These firms know that health care is relatively recession-proof, that providers have third-party payers, and that the industry is fragmented and requires more efficiency, Ms. Dooley said.

When PE practice acquisitions started gaining momentum about 12 years ago, traditional hospital-based specialties such as anesthesiology and radiology were prime targets, said Mr. Strode.

At the same time, increasing challenges in private practice, such as declining compensation from payers, pressure to participate in value-based care programs, and rising regional competitors have fueled more physician groups to partner with PE firms, Mr. Herschman noted.

Physicians who partner with PE firms often benefit by having new access to capital to grow their practices, cost savings through group purchasing, and the ability to compete with larger health groups, Mr. Herschman said.

Questions remain, however, about how PE involvement affects health care use and spending. An April 2023 JAMA Viewpoint article called out the lack of oversight and regulation in the health care/PE space, suggesting that a stronger framework for regulation and transparency is needed.

A 2022 study in JAMA Health Forum that examined changes in prices and utilization associated with the PE acquisitions of 578 dermatology, gastroenterology, and ophthalmology physician practices from 2016 to 2020 found that prices increased by an average of 11%, and volume rose by 16%, after acquisition.

“We found that acquisitions were associated with increases in health care spending and utilization, as well as some other patterns of care like potential upcoding,” said Jane M. Zhu, MD, an author of the study and assistant professor at Oregon Health & Science University in Portland.

Another recent study that Dr. Zhu coauthored, published in Health Affairs, found that physician practices acquired by PE firms experience greater staff turnover and rely more heavily on advanced practice professionals than doctors.

“To the extent that that turnover indicates physicians are dissatisfied after private equity comes in, that’s really important to investigate further,” Dr. Zhu said.

PE firms owned 4% of U.S. hospitals in 2021 and 11% of nursing homes, according to a Medicare Payment Advisory Commission (MedPAC) report. The report does not include 2021 data on medical practices but notes that from 2013 to 2016, PE firms acquired at least 2% of physician practices. Estimates of PE deals are probably lower than actual numbers because of the lack of comprehensive information sources, according to the MedPAC report.

A version of this article appeared on Medscape.com.

Men and women with prediabetes, undiagnosed diabetes, and, notably, diagnosed diabetes were at higher risk of incident cardiovascular disease (CVD), whereas those with low-normal A1c were at lower risk of this in a large, 12-year observational study of UK Biobank data.

The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.

The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.

“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.

After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.

Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).

“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
 

“The lower the better”

“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.

Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.

The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.

“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.

However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”

“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.

“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.

“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
 

More than 400,000 men, women

The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).

The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).

The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.

Few participants (5%) had any of these outcomes prior to study enrollment.

During the follow-up, there were 51,288 incident CVD events.

After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).

Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).

After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.

Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).

The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
 

A version of this article appeared on Medscape.com.

Men and women with prediabetes, undiagnosed diabetes, and, notably, diagnosed diabetes were at higher risk of incident cardiovascular disease (CVD), whereas those with low-normal A1c were at lower risk of this in a large, 12-year observational study of UK Biobank data.

The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.

The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.

“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.

After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.

Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).

“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
 

“The lower the better”

“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.

Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.

The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.

“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.

However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”

“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.

“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.

“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
 

More than 400,000 men, women

The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).

The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).

The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.

Few participants (5%) had any of these outcomes prior to study enrollment.

During the follow-up, there were 51,288 incident CVD events.

After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).

Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).

After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.

Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).

The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
 

A version of this article appeared on Medscape.com.

Men and women with prediabetes, undiagnosed diabetes, and, notably, diagnosed diabetes were at higher risk of incident cardiovascular disease (CVD), whereas those with low-normal A1c were at lower risk of this in a large, 12-year observational study of UK Biobank data.

The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.

The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.

“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.

After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.

Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).

“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
 

“The lower the better”

“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.

Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.

The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.

“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.

However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”

“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.

“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.

“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
 

More than 400,000 men, women

The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).

The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).

The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.

Few participants (5%) had any of these outcomes prior to study enrollment.

During the follow-up, there were 51,288 incident CVD events.

After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).

Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).

After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.

Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).

The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
 

A version of this article appeared on Medscape.com.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Should we be exercising in the morning or afternoon? Before a meal or after a meal?

Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But in reality, a gray zone exists, and/or a number of options are available. For me, exercise at any point of the day is a win.

Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.

But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.

But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.

The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).

But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).

I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.

Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!

It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
 

Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.

A version of this article first appeared on Medscape.com.

Should we be exercising in the morning or afternoon? Before a meal or after a meal?

Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But in reality, a gray zone exists, and/or a number of options are available. For me, exercise at any point of the day is a win.

Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.

But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.

But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.

The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).

But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).

I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.

Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!

It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
 

Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.

A version of this article first appeared on Medscape.com.

Should we be exercising in the morning or afternoon? Before a meal or after a meal?

Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But in reality, a gray zone exists, and/or a number of options are available. For me, exercise at any point of the day is a win.

Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.

But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.

But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.

The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).

But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).

I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.

Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!

It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
 

Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.

A version of this article first appeared on Medscape.com.

“We were all of us cogs in a great machine which sometimes rolled forward, nobody knew where, sometimes backwards, nobody knew why.” – Ernst Toller

A nice feature of the Apple watch is the stopwatch. With it, I can discreetly click the timer and watch seconds tick away. Tap. There’s one lap. Tap. Two. Tap. That was a quick visit, 6 minutes and 42 seconds. Tap. Under 2 minutes to close the chart. Let’s see if I can beat it. Tap. Tap. What if I moved my Mayo stand over to this side of the room? How about a sign, “All patients must have clothes off if you want a skin exam.” You think ob.gyns. are quick from skin to baby in a stat C-section? You should see how fast I can go from alcohol wipe to Drysol on a biopsy. Seconds. Tick, tick, tap.

Every day I look for ways to go faster. This is not so I can be out the door by 3. Rather, it’s simply to make it through the day without having to log on after we put the kids to bed at night.

Speaking of bedtimes, another nice feature of the Apple watch is the timer. With it, I can set a timer and a lovely chimey alarm will go off. This comes in handy with 3-year-olds. “Sloan, in two minutes we are going to brush your teeth.” Ding. “Sloan, you have one minute to get your pajamas on.” Ding. “Sloanie, I’ll give you 3 more minutes to put the kitties away, then get into bed.” Ding, ding, ding ...

As you can see, using the stopwatch to time a bedtime routine would be demoralizing. If you’ve tried to put a toddler to bed in summer you know. They explore every option to avoid sleeping: one more book (that would make 3), “accidentally” putting their pajamas on backwards, offering to brush their teeth a second time. And once the light is off, “Papa, I have to potty.” No, bedtime routines cannot be standardized. They resist being made efficient.

In contrast, we think of seeing patients as a standardizable process; work to be optimized. This idea that work should be as efficient as possible came from the father of business management, Frederick Taylor. Taylor, a mechanical engineer, observed inefficiencies on the factory floor. His work was seminal in the development of the second industrial revolution. Before then no one had applied scientific rigor to productivity. His book, “The Principles of Scientific Management,” written in 1909, is considered the most influential management book of the 20th century. He was the first to use stopwatches to perform time studies, noting how long each task took with the belief that there was one best way. The worker was an extension of the machine, tuned by management such that he was as efficient as possible.

PublicDomain/commons.wikimedia.org/wiki/File:Ford_assembly_line_-_1913.jpg

A more insidious downside on the drive to efficiency lies in the nature of what we do. We aren’t factory workers punching out widgets, we’re physicians caring for people and people cannot be standardized. In this way, seeing patients is more like putting a toddler to bed than like assembling an iPhone. There will always be by-the-ways, basal cells hiding behind the ear, traffic jams, and bags of products that they want to review. Not sure how to use your fluorouracil? Let’s go over it again. Need to talk more about why you have granuloma annulare? Let me explain. Despite Taylor’s vision, some work simply cannot be optimized. And shouldn’t.

“Where’s my 11:30 patient who checked in half an hour ago?!” I asked my medical assistant. “Oh, she had to go to the bathroom.” Tap.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

“We were all of us cogs in a great machine which sometimes rolled forward, nobody knew where, sometimes backwards, nobody knew why.” – Ernst Toller

A nice feature of the Apple watch is the stopwatch. With it, I can discreetly click the timer and watch seconds tick away. Tap. There’s one lap. Tap. Two. Tap. That was a quick visit, 6 minutes and 42 seconds. Tap. Under 2 minutes to close the chart. Let’s see if I can beat it. Tap. Tap. What if I moved my Mayo stand over to this side of the room? How about a sign, “All patients must have clothes off if you want a skin exam.” You think ob.gyns. are quick from skin to baby in a stat C-section? You should see how fast I can go from alcohol wipe to Drysol on a biopsy. Seconds. Tick, tick, tap.

Every day I look for ways to go faster. This is not so I can be out the door by 3. Rather, it’s simply to make it through the day without having to log on after we put the kids to bed at night.

Speaking of bedtimes, another nice feature of the Apple watch is the timer. With it, I can set a timer and a lovely chimey alarm will go off. This comes in handy with 3-year-olds. “Sloan, in two minutes we are going to brush your teeth.” Ding. “Sloan, you have one minute to get your pajamas on.” Ding. “Sloanie, I’ll give you 3 more minutes to put the kitties away, then get into bed.” Ding, ding, ding ...

As you can see, using the stopwatch to time a bedtime routine would be demoralizing. If you’ve tried to put a toddler to bed in summer you know. They explore every option to avoid sleeping: one more book (that would make 3), “accidentally” putting their pajamas on backwards, offering to brush their teeth a second time. And once the light is off, “Papa, I have to potty.” No, bedtime routines cannot be standardized. They resist being made efficient.

In contrast, we think of seeing patients as a standardizable process; work to be optimized. This idea that work should be as efficient as possible came from the father of business management, Frederick Taylor. Taylor, a mechanical engineer, observed inefficiencies on the factory floor. His work was seminal in the development of the second industrial revolution. Before then no one had applied scientific rigor to productivity. His book, “The Principles of Scientific Management,” written in 1909, is considered the most influential management book of the 20th century. He was the first to use stopwatches to perform time studies, noting how long each task took with the belief that there was one best way. The worker was an extension of the machine, tuned by management such that he was as efficient as possible.

PublicDomain/commons.wikimedia.org/wiki/File:Ford_assembly_line_-_1913.jpg

A more insidious downside on the drive to efficiency lies in the nature of what we do. We aren’t factory workers punching out widgets, we’re physicians caring for people and people cannot be standardized. In this way, seeing patients is more like putting a toddler to bed than like assembling an iPhone. There will always be by-the-ways, basal cells hiding behind the ear, traffic jams, and bags of products that they want to review. Not sure how to use your fluorouracil? Let’s go over it again. Need to talk more about why you have granuloma annulare? Let me explain. Despite Taylor’s vision, some work simply cannot be optimized. And shouldn’t.

“Where’s my 11:30 patient who checked in half an hour ago?!” I asked my medical assistant. “Oh, she had to go to the bathroom.” Tap.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

“We were all of us cogs in a great machine which sometimes rolled forward, nobody knew where, sometimes backwards, nobody knew why.” – Ernst Toller

A nice feature of the Apple watch is the stopwatch. With it, I can discreetly click the timer and watch seconds tick away. Tap. There’s one lap. Tap. Two. Tap. That was a quick visit, 6 minutes and 42 seconds. Tap. Under 2 minutes to close the chart. Let’s see if I can beat it. Tap. Tap. What if I moved my Mayo stand over to this side of the room? How about a sign, “All patients must have clothes off if you want a skin exam.” You think ob.gyns. are quick from skin to baby in a stat C-section? You should see how fast I can go from alcohol wipe to Drysol on a biopsy. Seconds. Tick, tick, tap.

Every day I look for ways to go faster. This is not so I can be out the door by 3. Rather, it’s simply to make it through the day without having to log on after we put the kids to bed at night.

Speaking of bedtimes, another nice feature of the Apple watch is the timer. With it, I can set a timer and a lovely chimey alarm will go off. This comes in handy with 3-year-olds. “Sloan, in two minutes we are going to brush your teeth.” Ding. “Sloan, you have one minute to get your pajamas on.” Ding. “Sloanie, I’ll give you 3 more minutes to put the kitties away, then get into bed.” Ding, ding, ding ...

As you can see, using the stopwatch to time a bedtime routine would be demoralizing. If you’ve tried to put a toddler to bed in summer you know. They explore every option to avoid sleeping: one more book (that would make 3), “accidentally” putting their pajamas on backwards, offering to brush their teeth a second time. And once the light is off, “Papa, I have to potty.” No, bedtime routines cannot be standardized. They resist being made efficient.

In contrast, we think of seeing patients as a standardizable process; work to be optimized. This idea that work should be as efficient as possible came from the father of business management, Frederick Taylor. Taylor, a mechanical engineer, observed inefficiencies on the factory floor. His work was seminal in the development of the second industrial revolution. Before then no one had applied scientific rigor to productivity. His book, “The Principles of Scientific Management,” written in 1909, is considered the most influential management book of the 20th century. He was the first to use stopwatches to perform time studies, noting how long each task took with the belief that there was one best way. The worker was an extension of the machine, tuned by management such that he was as efficient as possible.

PublicDomain/commons.wikimedia.org/wiki/File:Ford_assembly_line_-_1913.jpg

A more insidious downside on the drive to efficiency lies in the nature of what we do. We aren’t factory workers punching out widgets, we’re physicians caring for people and people cannot be standardized. In this way, seeing patients is more like putting a toddler to bed than like assembling an iPhone. There will always be by-the-ways, basal cells hiding behind the ear, traffic jams, and bags of products that they want to review. Not sure how to use your fluorouracil? Let’s go over it again. Need to talk more about why you have granuloma annulare? Let me explain. Despite Taylor’s vision, some work simply cannot be optimized. And shouldn’t.

“Where’s my 11:30 patient who checked in half an hour ago?!” I asked my medical assistant. “Oh, she had to go to the bathroom.” Tap.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

The Food and Drug Administration has approved palovarotene (Sohonos), the first-ever treatment for people with the rare and severely disabling bone condition fibrodysplasia ossificans progressiva (FOP).

Affecting roughly 400 people in the United States and 900 worldwide, FOP is an autosomal dominant condition in which bone develops in soft connective tissue areas of the body where it isn’t normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. This leads to severe restriction in mobility and function, to the point that people lose the ability to feed or care for themselves. Most are completely disabled by age 30 years and median life expectancy is 56 years, with death often caused by bone formation around the rib cage restricting respiration.

Olivier Le Moal/Getty Images

“As a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with ... since the accumulation of heterotopic ossification in FOP is progressive, irreversible, and life altering. This medication is an important treatment option for our FOP community,” said endocrinologist Edward Hsiao, MD, professor of medicine at the University of California, San Francisco, in a statement from Ipsen.

Taken orally, palovarotene selectively targets the gamma subtype of retinoic acid receptors that regulate skeletal development and ectopic bone in the retinoid signaling pathway. The drug mediates interactions between these receptors, growth factors, and proteins within that pathway to reduce new abnormal bone formation.

It is now FDA approved for the treatment of FOP in female patients aged 8 years or older and male patients aged 10 years or older. The recommended dosing is 5 mg daily or weight-based equivalent for pediatric patients under 14 years of age, which can be modified or increased for flare-up symptoms. It is contraindicated during pregnancy.

The FDA approval was based on 18-month data from the phase 3, multicenter, open-label MOVE trial that included 107 adult and pediatric patients, over 10% of the world’s population with FOP. All received oral palovarotene and were compared with untreated individuals from a prior natural history study of the condition. The drug reduced annualized heterotopic ossification volume by 54%.

Side effects were typical of those seen with other systemic retinoid drugs, including mucocutaneous events such as dryness of the skin and mucous membranes, alopecia, drug eruption, rash, and pruritus, and musculoskeletal events, such as arthralgia and premature growth plate closure in growing children.

According to Dr. Hsiao, who was a MOVE investigator, the study “showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP. Sohonos is not for everyone. As with all medicines there are risks in this case especially for young children who may develop early growth plate closure. In addition, Sohonos has the same side effects as other retinoids.”

The FDA approval of palovarotene follows its rejection for marketing authorization in the European Union in July 2023.

Reached for comment, an Ipsen spokesperson said in an interview: “We reached the end of the regulatory process in the European Union for Sohonos and are disappointed the European Commission decided not to approved palovarotene for people with FOP in Europe.”

The company is developing another drug, fidrisertib, for treating FOP. A pivotal phase 2 trial for that drug is now recruiting patients. Asked where Ipsen might try to market fidrisertib, the spokesperson replied:“At this point, our focus is on the completion of the pivotal trial.”

Meanwhile, in the United States, the FOP community is celebrating the palovarotene approval. In a statement, Michelle Davis, executive director of the International Fibrodysplasia Ossificans Progressiva Association, said: “FOP is life altering to the individuals diagnosed and their families. There’s not a day that goes by where those impacted don’t worry about the debilitating physical pain of muscle that is replaced by bone, another joint locking, or the relentless emotional toll of losing the ability to do an activity they love, or hold a loved one close. ... The first treatment for FOP has been proven to reduce the volume of new abnormal bone growth, which may result in better health outcomes for people living with FOP.”

Ipsen is offering a patient support program to assist with education, coverage, and reimbursement (1-866-435-5677).

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved palovarotene (Sohonos), the first-ever treatment for people with the rare and severely disabling bone condition fibrodysplasia ossificans progressiva (FOP).

Affecting roughly 400 people in the United States and 900 worldwide, FOP is an autosomal dominant condition in which bone develops in soft connective tissue areas of the body where it isn’t normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. This leads to severe restriction in mobility and function, to the point that people lose the ability to feed or care for themselves. Most are completely disabled by age 30 years and median life expectancy is 56 years, with death often caused by bone formation around the rib cage restricting respiration.

Olivier Le Moal/Getty Images

“As a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with ... since the accumulation of heterotopic ossification in FOP is progressive, irreversible, and life altering. This medication is an important treatment option for our FOP community,” said endocrinologist Edward Hsiao, MD, professor of medicine at the University of California, San Francisco, in a statement from Ipsen.

Taken orally, palovarotene selectively targets the gamma subtype of retinoic acid receptors that regulate skeletal development and ectopic bone in the retinoid signaling pathway. The drug mediates interactions between these receptors, growth factors, and proteins within that pathway to reduce new abnormal bone formation.

It is now FDA approved for the treatment of FOP in female patients aged 8 years or older and male patients aged 10 years or older. The recommended dosing is 5 mg daily or weight-based equivalent for pediatric patients under 14 years of age, which can be modified or increased for flare-up symptoms. It is contraindicated during pregnancy.

The FDA approval was based on 18-month data from the phase 3, multicenter, open-label MOVE trial that included 107 adult and pediatric patients, over 10% of the world’s population with FOP. All received oral palovarotene and were compared with untreated individuals from a prior natural history study of the condition. The drug reduced annualized heterotopic ossification volume by 54%.

Side effects were typical of those seen with other systemic retinoid drugs, including mucocutaneous events such as dryness of the skin and mucous membranes, alopecia, drug eruption, rash, and pruritus, and musculoskeletal events, such as arthralgia and premature growth plate closure in growing children.

According to Dr. Hsiao, who was a MOVE investigator, the study “showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP. Sohonos is not for everyone. As with all medicines there are risks in this case especially for young children who may develop early growth plate closure. In addition, Sohonos has the same side effects as other retinoids.”

The FDA approval of palovarotene follows its rejection for marketing authorization in the European Union in July 2023.

Reached for comment, an Ipsen spokesperson said in an interview: “We reached the end of the regulatory process in the European Union for Sohonos and are disappointed the European Commission decided not to approved palovarotene for people with FOP in Europe.”

The company is developing another drug, fidrisertib, for treating FOP. A pivotal phase 2 trial for that drug is now recruiting patients. Asked where Ipsen might try to market fidrisertib, the spokesperson replied:“At this point, our focus is on the completion of the pivotal trial.”

Meanwhile, in the United States, the FOP community is celebrating the palovarotene approval. In a statement, Michelle Davis, executive director of the International Fibrodysplasia Ossificans Progressiva Association, said: “FOP is life altering to the individuals diagnosed and their families. There’s not a day that goes by where those impacted don’t worry about the debilitating physical pain of muscle that is replaced by bone, another joint locking, or the relentless emotional toll of losing the ability to do an activity they love, or hold a loved one close. ... The first treatment for FOP has been proven to reduce the volume of new abnormal bone growth, which may result in better health outcomes for people living with FOP.”

Ipsen is offering a patient support program to assist with education, coverage, and reimbursement (1-866-435-5677).

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved palovarotene (Sohonos), the first-ever treatment for people with the rare and severely disabling bone condition fibrodysplasia ossificans progressiva (FOP).

Affecting roughly 400 people in the United States and 900 worldwide, FOP is an autosomal dominant condition in which bone develops in soft connective tissue areas of the body where it isn’t normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. This leads to severe restriction in mobility and function, to the point that people lose the ability to feed or care for themselves. Most are completely disabled by age 30 years and median life expectancy is 56 years, with death often caused by bone formation around the rib cage restricting respiration.

Olivier Le Moal/Getty Images

“As a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with ... since the accumulation of heterotopic ossification in FOP is progressive, irreversible, and life altering. This medication is an important treatment option for our FOP community,” said endocrinologist Edward Hsiao, MD, professor of medicine at the University of California, San Francisco, in a statement from Ipsen.

Taken orally, palovarotene selectively targets the gamma subtype of retinoic acid receptors that regulate skeletal development and ectopic bone in the retinoid signaling pathway. The drug mediates interactions between these receptors, growth factors, and proteins within that pathway to reduce new abnormal bone formation.

It is now FDA approved for the treatment of FOP in female patients aged 8 years or older and male patients aged 10 years or older. The recommended dosing is 5 mg daily or weight-based equivalent for pediatric patients under 14 years of age, which can be modified or increased for flare-up symptoms. It is contraindicated during pregnancy.

The FDA approval was based on 18-month data from the phase 3, multicenter, open-label MOVE trial that included 107 adult and pediatric patients, over 10% of the world’s population with FOP. All received oral palovarotene and were compared with untreated individuals from a prior natural history study of the condition. The drug reduced annualized heterotopic ossification volume by 54%.

Side effects were typical of those seen with other systemic retinoid drugs, including mucocutaneous events such as dryness of the skin and mucous membranes, alopecia, drug eruption, rash, and pruritus, and musculoskeletal events, such as arthralgia and premature growth plate closure in growing children.

According to Dr. Hsiao, who was a MOVE investigator, the study “showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP. Sohonos is not for everyone. As with all medicines there are risks in this case especially for young children who may develop early growth plate closure. In addition, Sohonos has the same side effects as other retinoids.”

The FDA approval of palovarotene follows its rejection for marketing authorization in the European Union in July 2023.

Reached for comment, an Ipsen spokesperson said in an interview: “We reached the end of the regulatory process in the European Union for Sohonos and are disappointed the European Commission decided not to approved palovarotene for people with FOP in Europe.”

The company is developing another drug, fidrisertib, for treating FOP. A pivotal phase 2 trial for that drug is now recruiting patients. Asked where Ipsen might try to market fidrisertib, the spokesperson replied:“At this point, our focus is on the completion of the pivotal trial.”

Meanwhile, in the United States, the FOP community is celebrating the palovarotene approval. In a statement, Michelle Davis, executive director of the International Fibrodysplasia Ossificans Progressiva Association, said: “FOP is life altering to the individuals diagnosed and their families. There’s not a day that goes by where those impacted don’t worry about the debilitating physical pain of muscle that is replaced by bone, another joint locking, or the relentless emotional toll of losing the ability to do an activity they love, or hold a loved one close. ... The first treatment for FOP has been proven to reduce the volume of new abnormal bone growth, which may result in better health outcomes for people living with FOP.”

Ipsen is offering a patient support program to assist with education, coverage, and reimbursement (1-866-435-5677).

A version of this article appeared on Medscape.com.

Sunday night. Las Vegas. Jason Aldean had just started playing.

My wife and I were at the 2017 Route 91 Harvest Festival with three other couples; two of them were our close friends. We were sitting in the VIP section, a tented area right next to the stage. We started hearing what I was convinced were fireworks.

I’ve been in the Army for 20 some years. I’ve been deployed and shot at multiple times. But these shots were far away. And you don’t expect people to be shooting at you at a concert.

I was on the edge of the VIP area, so I could see around the corner of the tent. I looked up at the Mandalay Bay and saw the muzzle flash in the hotel window. That’s when I knew.

I screamed: “Somebody’s shooting at us! Everybody get down!”

It took a while for people to realize what was going on. When the first couple volleys sprayed into the crowd, nobody understood. But once enough people had been hit and dropped, everyone knew, and it was just mass exodus.

People screamed and ran everywhere. Some of them tried to jump over the front barrier so they could get underneath the stage. Others were trying to pick up loved ones who’d been shot.

The next 15 minutes are a little foggy. I was helping my wife and the people around us to get down. Funny things come back to you afterward. One of my friends was carrying a 16-ounce beer in his hand. Somebody’s shooting at him and he’s walking around with his beer like he’s afraid to put it down. It was so surreal.

We got everybody underneath the tent, and then we just sat there. There would be shooting and then a pause. You’d think it was over. And then there would be more shooting and another pause. It felt like it never was going to stop.

After a short period of time, somebody came in with an official badge, maybe FBI, who knows. They said: “Okay, everybody up. We’ve got to get you out of here.” So, we all got up and headed across the stage. The gate they were taking us to was in full view of the shooter, so it wasn’t very safe.

As I got up, I looked out at the field. Bodies were scattered everywhere. I’m a trauma surgeon by trade. I couldn’t just leave.

I told my two best friends to take my wife with them. My wife lost her mind at that point. She didn’t want me to run out on the field. But I had to. I saw the injured and they needed help. Another buddy and I jumped over the fence and started taking care of people.

The feeling of being out on the field was one of complete frustration. I was in sandals, shorts, and a t-shirt. We had no stretchers, no medical supplies, no nothing. I didn’t have a belt to use as a tourniquet. I didn’t even have a bandage.

Worse: We were seeing high-velocity gunshot wounds that I’ve seen for 20 years in the Army. I know how to take care of them. I know how to fix them. But there wasn’t a single thing I could do.

We had to get people off the field, so we started gathering up as many as we could. We didn’t know if we were going to get shot at again, so we were trying to hide behind things as we ran. Our main objective was just to get people to a place of safety.

A lot of it is a blur. But a few patients stick out in my mind.

A father and son. The father had been shot through the abdomen, exited out through his back. He was in severe pain and couldn’t walk.

A young girl shot in the arm. Her parents carrying her.

A group of people doing CPR on a young lady. She had a gunshot wound to the head or neck. She was obviously dead. But they were still doing chest compressions in the middle of the field. I had to say to them: “She’s dead. You can’t save her. You need to get off the field.” But they wouldn’t stop. We picked her up and took her out while they continued to do CPR.

Later, I realized I knew that woman. She was part of a group of friends that we would see at the festival. I hadn’t recognized her. I also didn’t know that my friend Marco was there. A month or 2 later, we figured out that he was one of the people doing CPR. And I was the guy who came up and said his friend was dead.

Some people were so badly injured we couldn’t lift them. We started tearing apart the fencing used to separate the crowd and slid sections of the barricades under the wounded to carry them. We also carried off a bunch of people who were dead.

We were moving patients to a covered bar area where we thought they would be safer. What we didn’t know was there was an ambulance rally point at the very far end of the field. Unfortunately, we had no idea it was there.

I saw a lot of other first responders out there, people from the fire department, corpsmen from the Navy, medics. I ran into an anesthesia provider and a series of nurses.

When we got everybody off the field, we started moving them into vehicles. People were bringing their trucks up. One guy even stole a truck so he could drive people to the ED. There wasn’t a lot of triage. We were just stacking whoever we could into the backs of these pickups.

I tried to help a nurse taking care of a lady who had been shot in the neck. She was sitting sort of half upright with the patient lying in her arms. When I reached to help her, she said: “You can’t move her.”

“We need to get her to the hospital,” I replied.

“This is the only position that this lady has an airway,” she said. “You’re going to have to move both of us together. If I move at all, she loses her airway.”

So, a group of us managed to slide something underneath and lift them into the back of a truck.

Loading the wounded went on for a while. And then, just like that, everybody was gone.

I walked back out onto this field which not too long ago held 30,000 people. It was as if aliens had just suddenly beamed everyone out.

There was stuff on the ground everywhere – blankets, clothing, single boots, wallets, purses. I walked past a food stand with food still cooking on the grill. There was a beer tap still running. It was the weirdest feeling I’d ever had in my life.

After that, things got a little crazy again. There had been a report of a second shooter, and no one knew if it was real or not. The police started herding a group of us across the street to the Tropicana. We were still trying to take cover as we walked there. We went past a big lion statue in front of one of the casinos. I have a picture from two years earlier of me sitting on the back of that lion. I remember thinking: Now I’m hunkered down behind the same lion hiding from a shooter. Times change.

They brought about 50 of us into a food court, which was closed. They wouldn’t tell us what was going on. And they wouldn’t let us leave. This went on for hours. Meanwhile, I had dropped my cell phone on the field, so my wife couldn’t get hold of me, and later she told me she assumed I’d been shot. I was just hoping that she was safe.

People were huddled together, crying, holding each other. Most were wearing Western concert–going stuff, which for a lot of them wasn’t very much clothing. The hotel eventually brought some blankets.

I was covered in blood. My shirt, shorts, and sandals were soaked. It was running down my legs. I couldn’t find anything to eat or drink. At one point, I sat down at a slot machine, put a hundred dollars in, and started playing slots. I didn’t know what else to do. It didn’t take me very long to lose it all.

Finally, I started looking for a way to get out. I checked all the exits, but there were security and police there. Then I ran into a guy who said he had found a fire exit. When we opened the fire door, there was a big security guard there, and he said: “You can’t leave.”

We said: “Try to stop us. We’re out of here.”

Another thing I’ll always remember – after I broke out of the Tropicana, I was low crawling through the bushes along the Strip toward my hotel. I got a block away and stood up to cross the street. I pushed the crosswalk button and waited. There were no cars, no people. I’ve just broken all the rules, violated police orders, and now I’m standing there waiting for a blinking light to allow me to cross the street!

I made it back to my hotel room around 3:30 or 4:00 in the morning. My wife was hysterical because I hadn’t been answering my cell phone. I came in, and she gave me a big hug, and I got in the shower. Our plane was leaving in a few hours, so we laid down, but didn’t sleep.

As we were getting ready to leave, my wife’s phone rang, and it was my number. A guy at the same hotel had found my phone on the field and called the “in case of emergency” number. So, I got my phone back.

It wasn’t easy to deal with the aftermath. It really affected everybody’s life. To this day, I’m particular about where we sit at concerts. My wife isn’t comfortable if she can’t see an exit. I now have a med bag in my car with tourniquets, pressure dressings, airway masks for CPR.

I’ll never forget that feeling of absolute frustration. That lady without an airway – I could’ve put a trach in her very quickly and made a difference. Were they able to keep her airway? Did she live?

The father and son – did the father make it? I have no idea what happened to any of them. Later, I went through and looked at the pictures of all the people who had died, but I couldn’t recognize anybody.

The hardest part was being there with my wife. I’ve been in places where people are shooting at you, in vehicles that are getting bombed. I’ve always believed that when it’s your time, it’s your time. If I get shot, well, okay, that happens. But if she got shot or my friends ... that would be really tough.

A year later, I gave a talk about it at a conference. I thought I had worked through everything. But all of those feelings, all of that helplessness, that anger, everything came roaring back to the surface again. They asked me how I deal with it, and I said: “Well ... poorly.” I’m the guy who sticks it in a box in the back of his brain, tucks it in and buries it with a bunch of other boxes, and hopes it never comes out again. But every once in a while, it does.

There were all kinds of people out on that field, some with medical training, some without, all determined to help, trying to get those injured people where they needed to be. In retrospect, it does make you feel good. Somebody was shooting at us, but people were still willing to stand up and risk their lives to help others.

We still talk with our friends about what happened that night. Over the years, it’s become less and less. But there’s still a text sent out every year on that day: “Today is the anniversary. Glad we’re all alive. Thanks for being our friends.”

Dr. Sebesta is a bariatric surgeon with MultiCare Health System in Tacoma, Wash.

A version of this article first appeared on Medscape.com.

Sunday night. Las Vegas. Jason Aldean had just started playing.

My wife and I were at the 2017 Route 91 Harvest Festival with three other couples; two of them were our close friends. We were sitting in the VIP section, a tented area right next to the stage. We started hearing what I was convinced were fireworks.

I’ve been in the Army for 20 some years. I’ve been deployed and shot at multiple times. But these shots were far away. And you don’t expect people to be shooting at you at a concert.

I was on the edge of the VIP area, so I could see around the corner of the tent. I looked up at the Mandalay Bay and saw the muzzle flash in the hotel window. That’s when I knew.

I screamed: “Somebody’s shooting at us! Everybody get down!”

It took a while for people to realize what was going on. When the first couple volleys sprayed into the crowd, nobody understood. But once enough people had been hit and dropped, everyone knew, and it was just mass exodus.

People screamed and ran everywhere. Some of them tried to jump over the front barrier so they could get underneath the stage. Others were trying to pick up loved ones who’d been shot.

The next 15 minutes are a little foggy. I was helping my wife and the people around us to get down. Funny things come back to you afterward. One of my friends was carrying a 16-ounce beer in his hand. Somebody’s shooting at him and he’s walking around with his beer like he’s afraid to put it down. It was so surreal.

We got everybody underneath the tent, and then we just sat there. There would be shooting and then a pause. You’d think it was over. And then there would be more shooting and another pause. It felt like it never was going to stop.

After a short period of time, somebody came in with an official badge, maybe FBI, who knows. They said: “Okay, everybody up. We’ve got to get you out of here.” So, we all got up and headed across the stage. The gate they were taking us to was in full view of the shooter, so it wasn’t very safe.

As I got up, I looked out at the field. Bodies were scattered everywhere. I’m a trauma surgeon by trade. I couldn’t just leave.

I told my two best friends to take my wife with them. My wife lost her mind at that point. She didn’t want me to run out on the field. But I had to. I saw the injured and they needed help. Another buddy and I jumped over the fence and started taking care of people.

The feeling of being out on the field was one of complete frustration. I was in sandals, shorts, and a t-shirt. We had no stretchers, no medical supplies, no nothing. I didn’t have a belt to use as a tourniquet. I didn’t even have a bandage.

Worse: We were seeing high-velocity gunshot wounds that I’ve seen for 20 years in the Army. I know how to take care of them. I know how to fix them. But there wasn’t a single thing I could do.

We had to get people off the field, so we started gathering up as many as we could. We didn’t know if we were going to get shot at again, so we were trying to hide behind things as we ran. Our main objective was just to get people to a place of safety.

A lot of it is a blur. But a few patients stick out in my mind.

A father and son. The father had been shot through the abdomen, exited out through his back. He was in severe pain and couldn’t walk.

A young girl shot in the arm. Her parents carrying her.

A group of people doing CPR on a young lady. She had a gunshot wound to the head or neck. She was obviously dead. But they were still doing chest compressions in the middle of the field. I had to say to them: “She’s dead. You can’t save her. You need to get off the field.” But they wouldn’t stop. We picked her up and took her out while they continued to do CPR.

Later, I realized I knew that woman. She was part of a group of friends that we would see at the festival. I hadn’t recognized her. I also didn’t know that my friend Marco was there. A month or 2 later, we figured out that he was one of the people doing CPR. And I was the guy who came up and said his friend was dead.

Some people were so badly injured we couldn’t lift them. We started tearing apart the fencing used to separate the crowd and slid sections of the barricades under the wounded to carry them. We also carried off a bunch of people who were dead.

We were moving patients to a covered bar area where we thought they would be safer. What we didn’t know was there was an ambulance rally point at the very far end of the field. Unfortunately, we had no idea it was there.

I saw a lot of other first responders out there, people from the fire department, corpsmen from the Navy, medics. I ran into an anesthesia provider and a series of nurses.

When we got everybody off the field, we started moving them into vehicles. People were bringing their trucks up. One guy even stole a truck so he could drive people to the ED. There wasn’t a lot of triage. We were just stacking whoever we could into the backs of these pickups.

I tried to help a nurse taking care of a lady who had been shot in the neck. She was sitting sort of half upright with the patient lying in her arms. When I reached to help her, she said: “You can’t move her.”

“We need to get her to the hospital,” I replied.

“This is the only position that this lady has an airway,” she said. “You’re going to have to move both of us together. If I move at all, she loses her airway.”

So, a group of us managed to slide something underneath and lift them into the back of a truck.

Loading the wounded went on for a while. And then, just like that, everybody was gone.

I walked back out onto this field which not too long ago held 30,000 people. It was as if aliens had just suddenly beamed everyone out.

There was stuff on the ground everywhere – blankets, clothing, single boots, wallets, purses. I walked past a food stand with food still cooking on the grill. There was a beer tap still running. It was the weirdest feeling I’d ever had in my life.

After that, things got a little crazy again. There had been a report of a second shooter, and no one knew if it was real or not. The police started herding a group of us across the street to the Tropicana. We were still trying to take cover as we walked there. We went past a big lion statue in front of one of the casinos. I have a picture from two years earlier of me sitting on the back of that lion. I remember thinking: Now I’m hunkered down behind the same lion hiding from a shooter. Times change.

They brought about 50 of us into a food court, which was closed. They wouldn’t tell us what was going on. And they wouldn’t let us leave. This went on for hours. Meanwhile, I had dropped my cell phone on the field, so my wife couldn’t get hold of me, and later she told me she assumed I’d been shot. I was just hoping that she was safe.

People were huddled together, crying, holding each other. Most were wearing Western concert–going stuff, which for a lot of them wasn’t very much clothing. The hotel eventually brought some blankets.

I was covered in blood. My shirt, shorts, and sandals were soaked. It was running down my legs. I couldn’t find anything to eat or drink. At one point, I sat down at a slot machine, put a hundred dollars in, and started playing slots. I didn’t know what else to do. It didn’t take me very long to lose it all.

Finally, I started looking for a way to get out. I checked all the exits, but there were security and police there. Then I ran into a guy who said he had found a fire exit. When we opened the fire door, there was a big security guard there, and he said: “You can’t leave.”

We said: “Try to stop us. We’re out of here.”

Another thing I’ll always remember – after I broke out of the Tropicana, I was low crawling through the bushes along the Strip toward my hotel. I got a block away and stood up to cross the street. I pushed the crosswalk button and waited. There were no cars, no people. I’ve just broken all the rules, violated police orders, and now I’m standing there waiting for a blinking light to allow me to cross the street!

I made it back to my hotel room around 3:30 or 4:00 in the morning. My wife was hysterical because I hadn’t been answering my cell phone. I came in, and she gave me a big hug, and I got in the shower. Our plane was leaving in a few hours, so we laid down, but didn’t sleep.

As we were getting ready to leave, my wife’s phone rang, and it was my number. A guy at the same hotel had found my phone on the field and called the “in case of emergency” number. So, I got my phone back.

It wasn’t easy to deal with the aftermath. It really affected everybody’s life. To this day, I’m particular about where we sit at concerts. My wife isn’t comfortable if she can’t see an exit. I now have a med bag in my car with tourniquets, pressure dressings, airway masks for CPR.

I’ll never forget that feeling of absolute frustration. That lady without an airway – I could’ve put a trach in her very quickly and made a difference. Were they able to keep her airway? Did she live?

The father and son – did the father make it? I have no idea what happened to any of them. Later, I went through and looked at the pictures of all the people who had died, but I couldn’t recognize anybody.

The hardest part was being there with my wife. I’ve been in places where people are shooting at you, in vehicles that are getting bombed. I’ve always believed that when it’s your time, it’s your time. If I get shot, well, okay, that happens. But if she got shot or my friends ... that would be really tough.

A year later, I gave a talk about it at a conference. I thought I had worked through everything. But all of those feelings, all of that helplessness, that anger, everything came roaring back to the surface again. They asked me how I deal with it, and I said: “Well ... poorly.” I’m the guy who sticks it in a box in the back of his brain, tucks it in and buries it with a bunch of other boxes, and hopes it never comes out again. But every once in a while, it does.

There were all kinds of people out on that field, some with medical training, some without, all determined to help, trying to get those injured people where they needed to be. In retrospect, it does make you feel good. Somebody was shooting at us, but people were still willing to stand up and risk their lives to help others.

We still talk with our friends about what happened that night. Over the years, it’s become less and less. But there’s still a text sent out every year on that day: “Today is the anniversary. Glad we’re all alive. Thanks for being our friends.”

Dr. Sebesta is a bariatric surgeon with MultiCare Health System in Tacoma, Wash.

A version of this article first appeared on Medscape.com.

Sunday night. Las Vegas. Jason Aldean had just started playing.

My wife and I were at the 2017 Route 91 Harvest Festival with three other couples; two of them were our close friends. We were sitting in the VIP section, a tented area right next to the stage. We started hearing what I was convinced were fireworks.

I’ve been in the Army for 20 some years. I’ve been deployed and shot at multiple times. But these shots were far away. And you don’t expect people to be shooting at you at a concert.

I was on the edge of the VIP area, so I could see around the corner of the tent. I looked up at the Mandalay Bay and saw the muzzle flash in the hotel window. That’s when I knew.

I screamed: “Somebody’s shooting at us! Everybody get down!”

It took a while for people to realize what was going on. When the first couple volleys sprayed into the crowd, nobody understood. But once enough people had been hit and dropped, everyone knew, and it was just mass exodus.

People screamed and ran everywhere. Some of them tried to jump over the front barrier so they could get underneath the stage. Others were trying to pick up loved ones who’d been shot.

The next 15 minutes are a little foggy. I was helping my wife and the people around us to get down. Funny things come back to you afterward. One of my friends was carrying a 16-ounce beer in his hand. Somebody’s shooting at him and he’s walking around with his beer like he’s afraid to put it down. It was so surreal.

We got everybody underneath the tent, and then we just sat there. There would be shooting and then a pause. You’d think it was over. And then there would be more shooting and another pause. It felt like it never was going to stop.

After a short period of time, somebody came in with an official badge, maybe FBI, who knows. They said: “Okay, everybody up. We’ve got to get you out of here.” So, we all got up and headed across the stage. The gate they were taking us to was in full view of the shooter, so it wasn’t very safe.

As I got up, I looked out at the field. Bodies were scattered everywhere. I’m a trauma surgeon by trade. I couldn’t just leave.

I told my two best friends to take my wife with them. My wife lost her mind at that point. She didn’t want me to run out on the field. But I had to. I saw the injured and they needed help. Another buddy and I jumped over the fence and started taking care of people.

The feeling of being out on the field was one of complete frustration. I was in sandals, shorts, and a t-shirt. We had no stretchers, no medical supplies, no nothing. I didn’t have a belt to use as a tourniquet. I didn’t even have a bandage.

Worse: We were seeing high-velocity gunshot wounds that I’ve seen for 20 years in the Army. I know how to take care of them. I know how to fix them. But there wasn’t a single thing I could do.

We had to get people off the field, so we started gathering up as many as we could. We didn’t know if we were going to get shot at again, so we were trying to hide behind things as we ran. Our main objective was just to get people to a place of safety.

A lot of it is a blur. But a few patients stick out in my mind.

A father and son. The father had been shot through the abdomen, exited out through his back. He was in severe pain and couldn’t walk.

A young girl shot in the arm. Her parents carrying her.

A group of people doing CPR on a young lady. She had a gunshot wound to the head or neck. She was obviously dead. But they were still doing chest compressions in the middle of the field. I had to say to them: “She’s dead. You can’t save her. You need to get off the field.” But they wouldn’t stop. We picked her up and took her out while they continued to do CPR.

Later, I realized I knew that woman. She was part of a group of friends that we would see at the festival. I hadn’t recognized her. I also didn’t know that my friend Marco was there. A month or 2 later, we figured out that he was one of the people doing CPR. And I was the guy who came up and said his friend was dead.

Some people were so badly injured we couldn’t lift them. We started tearing apart the fencing used to separate the crowd and slid sections of the barricades under the wounded to carry them. We also carried off a bunch of people who were dead.

We were moving patients to a covered bar area where we thought they would be safer. What we didn’t know was there was an ambulance rally point at the very far end of the field. Unfortunately, we had no idea it was there.

I saw a lot of other first responders out there, people from the fire department, corpsmen from the Navy, medics. I ran into an anesthesia provider and a series of nurses.

When we got everybody off the field, we started moving them into vehicles. People were bringing their trucks up. One guy even stole a truck so he could drive people to the ED. There wasn’t a lot of triage. We were just stacking whoever we could into the backs of these pickups.

I tried to help a nurse taking care of a lady who had been shot in the neck. She was sitting sort of half upright with the patient lying in her arms. When I reached to help her, she said: “You can’t move her.”

“We need to get her to the hospital,” I replied.

“This is the only position that this lady has an airway,” she said. “You’re going to have to move both of us together. If I move at all, she loses her airway.”

So, a group of us managed to slide something underneath and lift them into the back of a truck.

Loading the wounded went on for a while. And then, just like that, everybody was gone.

I walked back out onto this field which not too long ago held 30,000 people. It was as if aliens had just suddenly beamed everyone out.

There was stuff on the ground everywhere – blankets, clothing, single boots, wallets, purses. I walked past a food stand with food still cooking on the grill. There was a beer tap still running. It was the weirdest feeling I’d ever had in my life.

After that, things got a little crazy again. There had been a report of a second shooter, and no one knew if it was real or not. The police started herding a group of us across the street to the Tropicana. We were still trying to take cover as we walked there. We went past a big lion statue in front of one of the casinos. I have a picture from two years earlier of me sitting on the back of that lion. I remember thinking: Now I’m hunkered down behind the same lion hiding from a shooter. Times change.

They brought about 50 of us into a food court, which was closed. They wouldn’t tell us what was going on. And they wouldn’t let us leave. This went on for hours. Meanwhile, I had dropped my cell phone on the field, so my wife couldn’t get hold of me, and later she told me she assumed I’d been shot. I was just hoping that she was safe.

People were huddled together, crying, holding each other. Most were wearing Western concert–going stuff, which for a lot of them wasn’t very much clothing. The hotel eventually brought some blankets.

I was covered in blood. My shirt, shorts, and sandals were soaked. It was running down my legs. I couldn’t find anything to eat or drink. At one point, I sat down at a slot machine, put a hundred dollars in, and started playing slots. I didn’t know what else to do. It didn’t take me very long to lose it all.

Finally, I started looking for a way to get out. I checked all the exits, but there were security and police there. Then I ran into a guy who said he had found a fire exit. When we opened the fire door, there was a big security guard there, and he said: “You can’t leave.”

We said: “Try to stop us. We’re out of here.”

Another thing I’ll always remember – after I broke out of the Tropicana, I was low crawling through the bushes along the Strip toward my hotel. I got a block away and stood up to cross the street. I pushed the crosswalk button and waited. There were no cars, no people. I’ve just broken all the rules, violated police orders, and now I’m standing there waiting for a blinking light to allow me to cross the street!

I made it back to my hotel room around 3:30 or 4:00 in the morning. My wife was hysterical because I hadn’t been answering my cell phone. I came in, and she gave me a big hug, and I got in the shower. Our plane was leaving in a few hours, so we laid down, but didn’t sleep.

As we were getting ready to leave, my wife’s phone rang, and it was my number. A guy at the same hotel had found my phone on the field and called the “in case of emergency” number. So, I got my phone back.

It wasn’t easy to deal with the aftermath. It really affected everybody’s life. To this day, I’m particular about where we sit at concerts. My wife isn’t comfortable if she can’t see an exit. I now have a med bag in my car with tourniquets, pressure dressings, airway masks for CPR.

I’ll never forget that feeling of absolute frustration. That lady without an airway – I could’ve put a trach in her very quickly and made a difference. Were they able to keep her airway? Did she live?

The father and son – did the father make it? I have no idea what happened to any of them. Later, I went through and looked at the pictures of all the people who had died, but I couldn’t recognize anybody.

The hardest part was being there with my wife. I’ve been in places where people are shooting at you, in vehicles that are getting bombed. I’ve always believed that when it’s your time, it’s your time. If I get shot, well, okay, that happens. But if she got shot or my friends ... that would be really tough.

A year later, I gave a talk about it at a conference. I thought I had worked through everything. But all of those feelings, all of that helplessness, that anger, everything came roaring back to the surface again. They asked me how I deal with it, and I said: “Well ... poorly.” I’m the guy who sticks it in a box in the back of his brain, tucks it in and buries it with a bunch of other boxes, and hopes it never comes out again. But every once in a while, it does.

There were all kinds of people out on that field, some with medical training, some without, all determined to help, trying to get those injured people where they needed to be. In retrospect, it does make you feel good. Somebody was shooting at us, but people were still willing to stand up and risk their lives to help others.

We still talk with our friends about what happened that night. Over the years, it’s become less and less. But there’s still a text sent out every year on that day: “Today is the anniversary. Glad we’re all alive. Thanks for being our friends.”

Dr. Sebesta is a bariatric surgeon with MultiCare Health System in Tacoma, Wash.

A version of this article first appeared on Medscape.com.

Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D. To help determine whether metformin has been “dethroned” as first-line treatment for T2D, here is a brief review of recent evidence and current guideline recommendations.

Cardiovascular outcome trials transform standard of care

In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.

Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.

During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.

Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
 

Individualizing care to attain cardiorenal-metabolic goals

Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.

As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.

The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.

In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m², and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
 

Optimizing guideline-directed medical therapy

Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.

So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.

Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.

A version of this article appeared on Medscape.com.

Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D. To help determine whether metformin has been “dethroned” as first-line treatment for T2D, here is a brief review of recent evidence and current guideline recommendations.

Cardiovascular outcome trials transform standard of care

In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.

Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.

During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.

Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
 

Individualizing care to attain cardiorenal-metabolic goals

Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.

As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.

The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.

In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m², and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
 

Optimizing guideline-directed medical therapy

Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.

So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.

Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.

A version of this article appeared on Medscape.com.

Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D. To help determine whether metformin has been “dethroned” as first-line treatment for T2D, here is a brief review of recent evidence and current guideline recommendations.

Cardiovascular outcome trials transform standard of care

In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.

Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.

During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.

Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
 

Individualizing care to attain cardiorenal-metabolic goals

Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.

As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.

The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.

In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m², and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
 

Optimizing guideline-directed medical therapy

Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.

So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.

Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.

A version of this article appeared on Medscape.com.

Genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain, a new study suggests.

People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.

However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.

These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.

The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.

“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.

“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.

Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.

If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.

“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.

Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”

“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”

In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.

“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”

“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”    
 

Maintaining weight loss is the big challenge

“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.

They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.

On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.

From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.

From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.

From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.

Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.

“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.

The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain, a new study suggests.

People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.

However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.

These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.

The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.

“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.

“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.

Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.

If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.

“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.

Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”

“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”

In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.

“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”

“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”    
 

Maintaining weight loss is the big challenge

“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.

They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.

On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.

From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.

From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.

From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.

Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.

“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.

The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain, a new study suggests.

People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.

However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.

These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.

The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.

“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.

“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.

Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.

If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.

“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.

Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”

“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”

In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.

“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”

“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”    
 

Maintaining weight loss is the big challenge

“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.

They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.

On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.

From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.

From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.

From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.

Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.

“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.

The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.