The following scenario was discussed during a forum at a meeting recently:

Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.

I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”

Physicians typically can’t identify with clock watching behavior, because we learned early on that patient-care tasks must be pursued to completion; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.

Utamaru Kido/Moment/Getty Images

A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.

Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.

Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:

1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.

2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.

3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.

4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.

5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.

6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.

7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.

8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.

9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.

10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

The following scenario was discussed during a forum at a meeting recently:

Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.

I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”

Physicians typically can’t identify with clock watching behavior, because we learned early on that patient-care tasks must be pursued to completion; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.

Utamaru Kido/Moment/Getty Images

A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.

Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.

Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:

1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.

2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.

3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.

4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.

5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.

6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.

7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.

8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.

9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.

10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

The following scenario was discussed during a forum at a meeting recently:

Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.

I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”

Physicians typically can’t identify with clock watching behavior, because we learned early on that patient-care tasks must be pursued to completion; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.

Utamaru Kido/Moment/Getty Images

A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.

Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.

Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:

1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.

2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.

3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.

4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.

5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.

6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.

7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.

8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.

9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.

10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

The US Food and Drug Administration (FDA) embraced the use of biomarkers and surrogate endpoints in its most recent guidance on developing therapeutics for early Alzheimer’s disease.

The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.

It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.

In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”

The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.

Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
 

A New POV

The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.

In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element. 

In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.

“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted. 

The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).

“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”

However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals. 
 

A Faster Pathway to Approval 

The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”

Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures. 

Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.

The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.

The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added. 

Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.

The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.” 

“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) embraced the use of biomarkers and surrogate endpoints in its most recent guidance on developing therapeutics for early Alzheimer’s disease.

The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.

It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.

In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”

The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.

Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
 

A New POV

The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.

In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element. 

In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.

“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted. 

The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).

“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”

However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals. 
 

A Faster Pathway to Approval 

The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”

Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures. 

Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.

The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.

The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added. 

Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.

The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.” 

“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) embraced the use of biomarkers and surrogate endpoints in its most recent guidance on developing therapeutics for early Alzheimer’s disease.

The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.

It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.

In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”

The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.

Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
 

A New POV

The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.

In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element. 

In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.

“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted. 

The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).

“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”

However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals. 
 

A Faster Pathway to Approval 

The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”

Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures. 

Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.

The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.

The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added. 

Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.

The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.” 

“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged men at high risk for Alzheimer’s disease (AD), higher pancreatic fat is linked to lower cognition and brain volumes.

METHODOLOGY:

• Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
• The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
• The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
• Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
• A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.

TAKEAWAY:

• High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
• After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
• In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
• Hepatic fat was not associated with brain volumes or cognition in either men or women.

IN PRACTICE:

“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.

SOURCE:

This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).

LIMITATIONS:

No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.

DISCLOSURES:

This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged men at high risk for Alzheimer’s disease (AD), higher pancreatic fat is linked to lower cognition and brain volumes.

METHODOLOGY:

• Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
• The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
• The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
• Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
• A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.

TAKEAWAY:

• High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
• After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
• In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
• Hepatic fat was not associated with brain volumes or cognition in either men or women.

IN PRACTICE:

“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.

SOURCE:

This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).

LIMITATIONS:

No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.

DISCLOSURES:

This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged men at high risk for Alzheimer’s disease (AD), higher pancreatic fat is linked to lower cognition and brain volumes.

METHODOLOGY:

• Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
• The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
• The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
• Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
• A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.

TAKEAWAY:

• High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
• After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
• In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
• Hepatic fat was not associated with brain volumes or cognition in either men or women.

IN PRACTICE:

“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.

SOURCE:

This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).

LIMITATIONS:

No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.

DISCLOSURES:

This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.