MDedge Endocrinology

Medtronic has updated a previous recall of its MiniMed 600 series insulin pumps to include all with a potentially problematic clear retainer ring, not just those that appear damaged.

The U.S. Food and Drug Administration announced on Oct. 5 that Medtronic will now replace any MiniMed 600 series pump that has a clear retainer ring with an updated pump that includes a black retainer ring at no extra charge, regardless of warranty status.

In November 2019, Medtronic first advised patients to examine their pumps for potential damage to the ring, and to contact the company if it appeared to be loose, damaged, or missing. In February 2020, the FDA designated the recall as class 1, “the most serious type of recall,” for which use of the devices “may cause serious injuries or death.”

In this case, one potential risk is hyperglycemia. This can occur if the reservoir isn’t properly locked into place by the retainer ring, and insulin isn’t infused into the body. That, in turn, can lead to diabetic ketoacidosis. Another risk is hypoglycemia, which could result from over-delivery of insulin if the retainer ring breaks or detaches and the user inserts the reservoir back into the pump with the infusion set still connected to the body.

While serious injuries and deaths have been reported with the use of Minimed series 600 insulin pumps, “those adverse events may not have been directly related to the damaged clear retainer rings that are the basis for this recall,” according to the FDA notice. Nonetheless, lawsuits have reportedly been filed.

The new update is not a result of any new issues, Medtronic spokesperson Pamela Reese told this news organization. “Medtronic will proactively replace all MiniMed 600 series insulin pumps with the clear retainer ring design with an equivalent pump that has an updated black retainer ring design, which is designed to better withstand damage sustained by an accidental drop or bump on a hard surface.”

She added, “As we analyze the information that we continuously collect on the safety and performance of our insulin pumps, we recognize that patients who are still using the clear retainer ring could potentially encounter future problems. Therefore, we are currently accelerating our replacement as inventory allows over the coming months to eliminate any potential performance concerns and optimize patient safety and experience.”

The company has replaced nearly half of the clear retainer ring pumps that were in use since November 2019, she said.

The specific insulin pump products are the model 630G, distributed between September 2016 and February 2020; and the 670G, distributed between May 2015 and December 2020. The 630G is approved for people aged 16 years and older, and the 670G – which works with a continuous glucose monitor in a “hybrid closed-loop system – is available for people with type 1 diabetes as young as 7 years of age.

Medtronic has updated a previous recall of its MiniMed 600 series insulin pumps to include all with a potentially problematic clear retainer ring, not just those that appear damaged.

The U.S. Food and Drug Administration announced on Oct. 5 that Medtronic will now replace any MiniMed 600 series pump that has a clear retainer ring with an updated pump that includes a black retainer ring at no extra charge, regardless of warranty status.

In November 2019, Medtronic first advised patients to examine their pumps for potential damage to the ring, and to contact the company if it appeared to be loose, damaged, or missing. In February 2020, the FDA designated the recall as class 1, “the most serious type of recall,” for which use of the devices “may cause serious injuries or death.”

In this case, one potential risk is hyperglycemia. This can occur if the reservoir isn’t properly locked into place by the retainer ring, and insulin isn’t infused into the body. That, in turn, can lead to diabetic ketoacidosis. Another risk is hypoglycemia, which could result from over-delivery of insulin if the retainer ring breaks or detaches and the user inserts the reservoir back into the pump with the infusion set still connected to the body.

While serious injuries and deaths have been reported with the use of Minimed series 600 insulin pumps, “those adverse events may not have been directly related to the damaged clear retainer rings that are the basis for this recall,” according to the FDA notice. Nonetheless, lawsuits have reportedly been filed.

The new update is not a result of any new issues, Medtronic spokesperson Pamela Reese told this news organization. “Medtronic will proactively replace all MiniMed 600 series insulin pumps with the clear retainer ring design with an equivalent pump that has an updated black retainer ring design, which is designed to better withstand damage sustained by an accidental drop or bump on a hard surface.”

She added, “As we analyze the information that we continuously collect on the safety and performance of our insulin pumps, we recognize that patients who are still using the clear retainer ring could potentially encounter future problems. Therefore, we are currently accelerating our replacement as inventory allows over the coming months to eliminate any potential performance concerns and optimize patient safety and experience.”

The company has replaced nearly half of the clear retainer ring pumps that were in use since November 2019, she said.

The specific insulin pump products are the model 630G, distributed between September 2016 and February 2020; and the 670G, distributed between May 2015 and December 2020. The 630G is approved for people aged 16 years and older, and the 670G – which works with a continuous glucose monitor in a “hybrid closed-loop system – is available for people with type 1 diabetes as young as 7 years of age.

Medtronic has updated a previous recall of its MiniMed 600 series insulin pumps to include all with a potentially problematic clear retainer ring, not just those that appear damaged.

The U.S. Food and Drug Administration announced on Oct. 5 that Medtronic will now replace any MiniMed 600 series pump that has a clear retainer ring with an updated pump that includes a black retainer ring at no extra charge, regardless of warranty status.

In November 2019, Medtronic first advised patients to examine their pumps for potential damage to the ring, and to contact the company if it appeared to be loose, damaged, or missing. In February 2020, the FDA designated the recall as class 1, “the most serious type of recall,” for which use of the devices “may cause serious injuries or death.”

In this case, one potential risk is hyperglycemia. This can occur if the reservoir isn’t properly locked into place by the retainer ring, and insulin isn’t infused into the body. That, in turn, can lead to diabetic ketoacidosis. Another risk is hypoglycemia, which could result from over-delivery of insulin if the retainer ring breaks or detaches and the user inserts the reservoir back into the pump with the infusion set still connected to the body.

While serious injuries and deaths have been reported with the use of Minimed series 600 insulin pumps, “those adverse events may not have been directly related to the damaged clear retainer rings that are the basis for this recall,” according to the FDA notice. Nonetheless, lawsuits have reportedly been filed.

The new update is not a result of any new issues, Medtronic spokesperson Pamela Reese told this news organization. “Medtronic will proactively replace all MiniMed 600 series insulin pumps with the clear retainer ring design with an equivalent pump that has an updated black retainer ring design, which is designed to better withstand damage sustained by an accidental drop or bump on a hard surface.”

She added, “As we analyze the information that we continuously collect on the safety and performance of our insulin pumps, we recognize that patients who are still using the clear retainer ring could potentially encounter future problems. Therefore, we are currently accelerating our replacement as inventory allows over the coming months to eliminate any potential performance concerns and optimize patient safety and experience.”

The company has replaced nearly half of the clear retainer ring pumps that were in use since November 2019, she said.

The specific insulin pump products are the model 630G, distributed between September 2016 and February 2020; and the 670G, distributed between May 2015 and December 2020. The 630G is approved for people aged 16 years and older, and the 670G – which works with a continuous glucose monitor in a “hybrid closed-loop system – is available for people with type 1 diabetes as young as 7 years of age.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

Johnson & Johnson asked the Food and Drug Administration (FDA) on Tuesday to authorize an extra dose of its COVID-19 vaccine as a booster shot.

The company said it filed a request for people ages 18 and older who have received the one-shot vaccine. Johnson & Johnson submitted data for several different booster intervals -- ranging from 2 months to 6 months -- but didn’t formally recommend one to the FDA, The Associated Press reported.

“We’re describing the data to them,” Mathai Mammen, MD, head of global research and development for Janssen, the company’s vaccine division, told CNN.

“The process is not that we asked for a very specific interval -- we’re providing them data and we’re going to be presenting to the committee,” he said. “They’ll take all that into consideration when they ultimately decide on an appropriate interval.”

The FDA’s independent vaccine advisory committee meets next week to review data on booster shots from both Johnson & Johnson and Moderna. It’s the first step in the review process, which then requires approval from leaders at the FDA and Centers for Disease Control and Prevention. If both agencies authorize the extra shots, Americans could receive boosters from Johnson & Johnson and Moderna later this month, the AP reported.

Johnson & Johnson previously released data that showed the vaccine remains highly effective against COVID-19 at least 5 months after vaccination, with 81% efficacy against hospitalizations in the United States.

Two weeks ago, the company reported that a booster dose at 2 months or 6 months further lifted immunity, with a booster at 2 months providing 94% protection against moderate and severe COVID-19. The company said the 6-month booster raised antibodies by 12 times but didn’t release additional data at that time.

In September, the FDA authorized booster shots of the Pfizer vaccine for ages 65 and older, those who live in long-term care facilities, and those with higher risks for contracting COVID-19. The Biden administration is supporting a booster campaign to address potential waning vaccine immunity and remaining surges of the more contagious Delta variant, the AP reported.

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

Johnson & Johnson asked the Food and Drug Administration (FDA) on Tuesday to authorize an extra dose of its COVID-19 vaccine as a booster shot.

The company said it filed a request for people ages 18 and older who have received the one-shot vaccine. Johnson & Johnson submitted data for several different booster intervals -- ranging from 2 months to 6 months -- but didn’t formally recommend one to the FDA, The Associated Press reported.

“We’re describing the data to them,” Mathai Mammen, MD, head of global research and development for Janssen, the company’s vaccine division, told CNN.

“The process is not that we asked for a very specific interval -- we’re providing them data and we’re going to be presenting to the committee,” he said. “They’ll take all that into consideration when they ultimately decide on an appropriate interval.”

The FDA’s independent vaccine advisory committee meets next week to review data on booster shots from both Johnson & Johnson and Moderna. It’s the first step in the review process, which then requires approval from leaders at the FDA and Centers for Disease Control and Prevention. If both agencies authorize the extra shots, Americans could receive boosters from Johnson & Johnson and Moderna later this month, the AP reported.

Johnson & Johnson previously released data that showed the vaccine remains highly effective against COVID-19 at least 5 months after vaccination, with 81% efficacy against hospitalizations in the United States.

Two weeks ago, the company reported that a booster dose at 2 months or 6 months further lifted immunity, with a booster at 2 months providing 94% protection against moderate and severe COVID-19. The company said the 6-month booster raised antibodies by 12 times but didn’t release additional data at that time.

In September, the FDA authorized booster shots of the Pfizer vaccine for ages 65 and older, those who live in long-term care facilities, and those with higher risks for contracting COVID-19. The Biden administration is supporting a booster campaign to address potential waning vaccine immunity and remaining surges of the more contagious Delta variant, the AP reported.

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

Johnson & Johnson asked the Food and Drug Administration (FDA) on Tuesday to authorize an extra dose of its COVID-19 vaccine as a booster shot.

The company said it filed a request for people ages 18 and older who have received the one-shot vaccine. Johnson & Johnson submitted data for several different booster intervals -- ranging from 2 months to 6 months -- but didn’t formally recommend one to the FDA, The Associated Press reported.

“We’re describing the data to them,” Mathai Mammen, MD, head of global research and development for Janssen, the company’s vaccine division, told CNN.

“The process is not that we asked for a very specific interval -- we’re providing them data and we’re going to be presenting to the committee,” he said. “They’ll take all that into consideration when they ultimately decide on an appropriate interval.”

The FDA’s independent vaccine advisory committee meets next week to review data on booster shots from both Johnson & Johnson and Moderna. It’s the first step in the review process, which then requires approval from leaders at the FDA and Centers for Disease Control and Prevention. If both agencies authorize the extra shots, Americans could receive boosters from Johnson & Johnson and Moderna later this month, the AP reported.

Johnson & Johnson previously released data that showed the vaccine remains highly effective against COVID-19 at least 5 months after vaccination, with 81% efficacy against hospitalizations in the United States.

Two weeks ago, the company reported that a booster dose at 2 months or 6 months further lifted immunity, with a booster at 2 months providing 94% protection against moderate and severe COVID-19. The company said the 6-month booster raised antibodies by 12 times but didn’t release additional data at that time.

In September, the FDA authorized booster shots of the Pfizer vaccine for ages 65 and older, those who live in long-term care facilities, and those with higher risks for contracting COVID-19. The Biden administration is supporting a booster campaign to address potential waning vaccine immunity and remaining surges of the more contagious Delta variant, the AP reported.

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

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

[email protected]

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

[email protected]

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

[email protected]

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

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

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

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

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.