MDedge Endocrinology

Amid rising concern about the potential long-term costs of using glucagon-like peptide 1 (GLP-1) agonists to treat obesity, some insurers are making access to bariatric surgery easier.

While the relationship may not be entirely causal, data do suggest that at least for now, these new agents for treating obesity including semaglutide (Wegovy) and tirzepatide (Zepbound) are not cost-effective, whereas the surgery is.

According to GoodRx, Wegovy (semaglutide) has a list price of about $1350 for a 28-day supply. And the American Society for Metabolic and Bariatric Surgery (ASMBS) said that the average cost of bariatric surgery ranges between $17,000 and $26,000. But ASMBS added that third-party payers will recover those costs within 2-4 years due to reduction or elimination of obesity-related conditions and associated treatment costs, with an approximate 29% healthcare cost reduction at 5 years.

Recently, for example, Geisinger Health of Pennsylvania and Blue Cross/Blue Shield of Massachusetts expanded body mass index (BMI) eligibility for bariatric surgery procedures, while Blue Cross Blue Shield of Michigan dropped prior authorization requirements for several services, including bariatric surgery.

While most major health insurers cover Wegovy for obesity treatment, they typically require prior authorization and/or trials of other therapies first. Recently, some employers have denied coverage for the medications for treating obesity. Medicare does not cover these drugs. Coverage varies across state Medicaid plans.

“For years, insurers…have played games with the surgery, making people jump through hoops, hoping that they would just give up and go away. And now that health plans are getting concerned about [the cost of] drugs for obesity, and they’re getting so much attention, they’re thinking oh, maybe we shouldn’t be playing these games anymore,” obesity policy expert Ted Kyle, RPh, founder of ConscienHealth, told this news organization.

However, Christopher Doubet Still, DO, director of Nutrition and Weight Management at Geisinger Medical Center, Danville, Pennsylvania, told this news organization that Geisinger Health Plan’s change in May 2023 to lower the BMI surgery eligibility cutoff from 35 kg/m2 to 30 kg/m2 for people with comorbidities was not related to the cost of GLP-1 drugs.

“To date, bariatric surgery remains the most effective, enduring treatment of obesity, and most importantly, its comorbid medical problems. So that was really the reasoning. The weight loss is secondary to the profound medical benefits of bariatric surgery. I think that was the impetus of that change, not having really anything to do at the time with GLP-1s,” Dr. Still said.

The Geisinger Health Plan does not currently cover antiobesity medications, although Geisinger Health Plan Family, a state Medicaid plan, does because Pennsylvania is now one of a handful of states that cover the medications through Medicaid.
 

The Equation Keeps Changing

Health economist James Chambers, PhD, of Tufts University, Boston, Massachusetts, told this news organizations, “when you think about the value of a treatment, you don’t look at it in isolation. You’re looking at the difference in cost and benefits. So now that you have these expensive drugs, it’s not that surgeries become less expensive, but it does make you interpret the cost differently. When diet and exercise and counseling were the only real options, surgeries seemed like a much more expensive intervention. But with the advent of the GLP-1s, then, maybe plans consider the costs of surgery a little bit differently.”

And that equation is likely to change further, Dr. Still noted.

“I just think we’re dealing with a short-term financial problem because there’s basically only two main medications so the prices are high, but as more medications come on the market, the prices will come down,” he said.

Cristy Ms. Gallagher, MPAff, research project director of the STOP Obesity Alliance at the Milken Institute School of Public Health at George Washington University, Washington, DC, agreed.

“We have a lot of data on obesity treatment coverage from before 2023. But then this [GLP-1] explosion happened in 2023…The health payers are out there trying to figure out coverage, and they’re trying to figure out what this is going to look like for them,” Ms. Gallagher said.

However, she pointed out, “there is no treatment that fits everyone. The GLP-1s won’t work for every person because of the different stages of obesity, the side effects, and then because of the coverage. I think that you will not see a decrease in bariatric surgery in the near term, by any means.”

Ms. Gallagher also noted that although the data now suggest people will have to keep taking the drugs for life, there may be other future approaches.

“Once a person hits their goal weight, maybe then they could be transferred to a different pill form that might be cheaper, something that’s sort of more of a maintenance drug. I think that is a huge unknown right now,” she said.

And Mr. Kyle said that while bariatric surgery does provide the most durable benefit, “weight regain after surgery is a fact of life. People are still healthier 5 years later, but they do have some weight regain. And in those cases, you might want to follow-up with medicines…It’s not necessarily an either/or proposition any more than surgical treatment of cancer, surgical oncology is an either/or with medical oncology.”
 

A New View of Obesity

According to Mr. Kyle, all this attention on the new medications “is prompting people to rethink or think differently about obesity and consider it more carefully as a chronic medical condition and not a condition of appearance and behavior. And that’s all good, whether you’re thinking about it from the standpoint of bariatric surgery or from the standpoint of medical treatment of obesity because then people start considering options more rationally.”

This shifting view of obesity has meant that bariatric surgeons and medical obesity specialists are starting to work more collaboratively, he said.

“There is a trend that I detect toward more integrated approaches to obesity,” Mr. Kyle said.

He added, “We now have more tools. And we’re in the messy middle of figuring out how, as a practical matter, to use them.”

And as far as insurance coverage, “people are going to make mistakes. They are making mistakes. But I have been the eternal optimist, and I have faith that people are also figuring it out. It would be hard to do worse.”

For now, any initiatives to increase bariatric surgery rates in the GLP-1 era haven’t yet had an impact, American Society for Metabolic and Bariatric Surgery President Marina S. Kurian, MD, told this news organization in a statement.

“While we have heard of some insurers possibly changing their requirements for bariatric surgery, we have not seen a significant rise in procedures related to changes in insurance coverage for either antiobesity medications or metabolic and bariatric surgery,” Dr. Kurian said.

Mr. Kyle had accepted speaking or professional fees from Novo Nordisk, Behringer Ingelheim, Nutrisystem, Roman Health, and Emerald Lake Safety. Dr. Still was on the speaker’s bureau and did clinical trials for Eli Lilly and Novo Nordisk. Dr. Chambers and Gallagher had no disclosures.

A version of this article appeared on Medscape.com.

Amid rising concern about the potential long-term costs of using glucagon-like peptide 1 (GLP-1) agonists to treat obesity, some insurers are making access to bariatric surgery easier.

While the relationship may not be entirely causal, data do suggest that at least for now, these new agents for treating obesity including semaglutide (Wegovy) and tirzepatide (Zepbound) are not cost-effective, whereas the surgery is.

According to GoodRx, Wegovy (semaglutide) has a list price of about $1350 for a 28-day supply. And the American Society for Metabolic and Bariatric Surgery (ASMBS) said that the average cost of bariatric surgery ranges between $17,000 and $26,000. But ASMBS added that third-party payers will recover those costs within 2-4 years due to reduction or elimination of obesity-related conditions and associated treatment costs, with an approximate 29% healthcare cost reduction at 5 years.

Recently, for example, Geisinger Health of Pennsylvania and Blue Cross/Blue Shield of Massachusetts expanded body mass index (BMI) eligibility for bariatric surgery procedures, while Blue Cross Blue Shield of Michigan dropped prior authorization requirements for several services, including bariatric surgery.

While most major health insurers cover Wegovy for obesity treatment, they typically require prior authorization and/or trials of other therapies first. Recently, some employers have denied coverage for the medications for treating obesity. Medicare does not cover these drugs. Coverage varies across state Medicaid plans.

“For years, insurers…have played games with the surgery, making people jump through hoops, hoping that they would just give up and go away. And now that health plans are getting concerned about [the cost of] drugs for obesity, and they’re getting so much attention, they’re thinking oh, maybe we shouldn’t be playing these games anymore,” obesity policy expert Ted Kyle, RPh, founder of ConscienHealth, told this news organization.

However, Christopher Doubet Still, DO, director of Nutrition and Weight Management at Geisinger Medical Center, Danville, Pennsylvania, told this news organization that Geisinger Health Plan’s change in May 2023 to lower the BMI surgery eligibility cutoff from 35 kg/m2 to 30 kg/m2 for people with comorbidities was not related to the cost of GLP-1 drugs.

“To date, bariatric surgery remains the most effective, enduring treatment of obesity, and most importantly, its comorbid medical problems. So that was really the reasoning. The weight loss is secondary to the profound medical benefits of bariatric surgery. I think that was the impetus of that change, not having really anything to do at the time with GLP-1s,” Dr. Still said.

The Geisinger Health Plan does not currently cover antiobesity medications, although Geisinger Health Plan Family, a state Medicaid plan, does because Pennsylvania is now one of a handful of states that cover the medications through Medicaid.
 

The Equation Keeps Changing

Health economist James Chambers, PhD, of Tufts University, Boston, Massachusetts, told this news organizations, “when you think about the value of a treatment, you don’t look at it in isolation. You’re looking at the difference in cost and benefits. So now that you have these expensive drugs, it’s not that surgeries become less expensive, but it does make you interpret the cost differently. When diet and exercise and counseling were the only real options, surgeries seemed like a much more expensive intervention. But with the advent of the GLP-1s, then, maybe plans consider the costs of surgery a little bit differently.”

And that equation is likely to change further, Dr. Still noted.

“I just think we’re dealing with a short-term financial problem because there’s basically only two main medications so the prices are high, but as more medications come on the market, the prices will come down,” he said.

Cristy Ms. Gallagher, MPAff, research project director of the STOP Obesity Alliance at the Milken Institute School of Public Health at George Washington University, Washington, DC, agreed.

“We have a lot of data on obesity treatment coverage from before 2023. But then this [GLP-1] explosion happened in 2023…The health payers are out there trying to figure out coverage, and they’re trying to figure out what this is going to look like for them,” Ms. Gallagher said.

However, she pointed out, “there is no treatment that fits everyone. The GLP-1s won’t work for every person because of the different stages of obesity, the side effects, and then because of the coverage. I think that you will not see a decrease in bariatric surgery in the near term, by any means.”

Ms. Gallagher also noted that although the data now suggest people will have to keep taking the drugs for life, there may be other future approaches.

“Once a person hits their goal weight, maybe then they could be transferred to a different pill form that might be cheaper, something that’s sort of more of a maintenance drug. I think that is a huge unknown right now,” she said.

And Mr. Kyle said that while bariatric surgery does provide the most durable benefit, “weight regain after surgery is a fact of life. People are still healthier 5 years later, but they do have some weight regain. And in those cases, you might want to follow-up with medicines…It’s not necessarily an either/or proposition any more than surgical treatment of cancer, surgical oncology is an either/or with medical oncology.”
 

A New View of Obesity

According to Mr. Kyle, all this attention on the new medications “is prompting people to rethink or think differently about obesity and consider it more carefully as a chronic medical condition and not a condition of appearance and behavior. And that’s all good, whether you’re thinking about it from the standpoint of bariatric surgery or from the standpoint of medical treatment of obesity because then people start considering options more rationally.”

This shifting view of obesity has meant that bariatric surgeons and medical obesity specialists are starting to work more collaboratively, he said.

“There is a trend that I detect toward more integrated approaches to obesity,” Mr. Kyle said.

He added, “We now have more tools. And we’re in the messy middle of figuring out how, as a practical matter, to use them.”

And as far as insurance coverage, “people are going to make mistakes. They are making mistakes. But I have been the eternal optimist, and I have faith that people are also figuring it out. It would be hard to do worse.”

For now, any initiatives to increase bariatric surgery rates in the GLP-1 era haven’t yet had an impact, American Society for Metabolic and Bariatric Surgery President Marina S. Kurian, MD, told this news organization in a statement.

“While we have heard of some insurers possibly changing their requirements for bariatric surgery, we have not seen a significant rise in procedures related to changes in insurance coverage for either antiobesity medications or metabolic and bariatric surgery,” Dr. Kurian said.

Mr. Kyle had accepted speaking or professional fees from Novo Nordisk, Behringer Ingelheim, Nutrisystem, Roman Health, and Emerald Lake Safety. Dr. Still was on the speaker’s bureau and did clinical trials for Eli Lilly and Novo Nordisk. Dr. Chambers and Gallagher had no disclosures.

A version of this article appeared on Medscape.com.

Amid rising concern about the potential long-term costs of using glucagon-like peptide 1 (GLP-1) agonists to treat obesity, some insurers are making access to bariatric surgery easier.

While the relationship may not be entirely causal, data do suggest that at least for now, these new agents for treating obesity including semaglutide (Wegovy) and tirzepatide (Zepbound) are not cost-effective, whereas the surgery is.

According to GoodRx, Wegovy (semaglutide) has a list price of about $1350 for a 28-day supply. And the American Society for Metabolic and Bariatric Surgery (ASMBS) said that the average cost of bariatric surgery ranges between $17,000 and $26,000. But ASMBS added that third-party payers will recover those costs within 2-4 years due to reduction or elimination of obesity-related conditions and associated treatment costs, with an approximate 29% healthcare cost reduction at 5 years.

Recently, for example, Geisinger Health of Pennsylvania and Blue Cross/Blue Shield of Massachusetts expanded body mass index (BMI) eligibility for bariatric surgery procedures, while Blue Cross Blue Shield of Michigan dropped prior authorization requirements for several services, including bariatric surgery.

While most major health insurers cover Wegovy for obesity treatment, they typically require prior authorization and/or trials of other therapies first. Recently, some employers have denied coverage for the medications for treating obesity. Medicare does not cover these drugs. Coverage varies across state Medicaid plans.

“For years, insurers…have played games with the surgery, making people jump through hoops, hoping that they would just give up and go away. And now that health plans are getting concerned about [the cost of] drugs for obesity, and they’re getting so much attention, they’re thinking oh, maybe we shouldn’t be playing these games anymore,” obesity policy expert Ted Kyle, RPh, founder of ConscienHealth, told this news organization.

However, Christopher Doubet Still, DO, director of Nutrition and Weight Management at Geisinger Medical Center, Danville, Pennsylvania, told this news organization that Geisinger Health Plan’s change in May 2023 to lower the BMI surgery eligibility cutoff from 35 kg/m2 to 30 kg/m2 for people with comorbidities was not related to the cost of GLP-1 drugs.

“To date, bariatric surgery remains the most effective, enduring treatment of obesity, and most importantly, its comorbid medical problems. So that was really the reasoning. The weight loss is secondary to the profound medical benefits of bariatric surgery. I think that was the impetus of that change, not having really anything to do at the time with GLP-1s,” Dr. Still said.

The Geisinger Health Plan does not currently cover antiobesity medications, although Geisinger Health Plan Family, a state Medicaid plan, does because Pennsylvania is now one of a handful of states that cover the medications through Medicaid.
 

The Equation Keeps Changing

Health economist James Chambers, PhD, of Tufts University, Boston, Massachusetts, told this news organizations, “when you think about the value of a treatment, you don’t look at it in isolation. You’re looking at the difference in cost and benefits. So now that you have these expensive drugs, it’s not that surgeries become less expensive, but it does make you interpret the cost differently. When diet and exercise and counseling were the only real options, surgeries seemed like a much more expensive intervention. But with the advent of the GLP-1s, then, maybe plans consider the costs of surgery a little bit differently.”

And that equation is likely to change further, Dr. Still noted.

“I just think we’re dealing with a short-term financial problem because there’s basically only two main medications so the prices are high, but as more medications come on the market, the prices will come down,” he said.

Cristy Ms. Gallagher, MPAff, research project director of the STOP Obesity Alliance at the Milken Institute School of Public Health at George Washington University, Washington, DC, agreed.

“We have a lot of data on obesity treatment coverage from before 2023. But then this [GLP-1] explosion happened in 2023…The health payers are out there trying to figure out coverage, and they’re trying to figure out what this is going to look like for them,” Ms. Gallagher said.

However, she pointed out, “there is no treatment that fits everyone. The GLP-1s won’t work for every person because of the different stages of obesity, the side effects, and then because of the coverage. I think that you will not see a decrease in bariatric surgery in the near term, by any means.”

Ms. Gallagher also noted that although the data now suggest people will have to keep taking the drugs for life, there may be other future approaches.

“Once a person hits their goal weight, maybe then they could be transferred to a different pill form that might be cheaper, something that’s sort of more of a maintenance drug. I think that is a huge unknown right now,” she said.

And Mr. Kyle said that while bariatric surgery does provide the most durable benefit, “weight regain after surgery is a fact of life. People are still healthier 5 years later, but they do have some weight regain. And in those cases, you might want to follow-up with medicines…It’s not necessarily an either/or proposition any more than surgical treatment of cancer, surgical oncology is an either/or with medical oncology.”
 

A New View of Obesity

According to Mr. Kyle, all this attention on the new medications “is prompting people to rethink or think differently about obesity and consider it more carefully as a chronic medical condition and not a condition of appearance and behavior. And that’s all good, whether you’re thinking about it from the standpoint of bariatric surgery or from the standpoint of medical treatment of obesity because then people start considering options more rationally.”

This shifting view of obesity has meant that bariatric surgeons and medical obesity specialists are starting to work more collaboratively, he said.

“There is a trend that I detect toward more integrated approaches to obesity,” Mr. Kyle said.

He added, “We now have more tools. And we’re in the messy middle of figuring out how, as a practical matter, to use them.”

And as far as insurance coverage, “people are going to make mistakes. They are making mistakes. But I have been the eternal optimist, and I have faith that people are also figuring it out. It would be hard to do worse.”

For now, any initiatives to increase bariatric surgery rates in the GLP-1 era haven’t yet had an impact, American Society for Metabolic and Bariatric Surgery President Marina S. Kurian, MD, told this news organization in a statement.

“While we have heard of some insurers possibly changing their requirements for bariatric surgery, we have not seen a significant rise in procedures related to changes in insurance coverage for either antiobesity medications or metabolic and bariatric surgery,” Dr. Kurian said.

Mr. Kyle had accepted speaking or professional fees from Novo Nordisk, Behringer Ingelheim, Nutrisystem, Roman Health, and Emerald Lake Safety. Dr. Still was on the speaker’s bureau and did clinical trials for Eli Lilly and Novo Nordisk. Dr. Chambers and Gallagher had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Anti-osteoporosis medications reduce fracture risk similarly, regardless of whether patients are younger or older than 70 years.

METHODOLOGY:

• Investigators conducted the study as part of a  to assess bone mineral density as a surrogate marker for fracture risk.
• Analyses used individual patient data from 23 randomized placebo-controlled trials of anti-osteoporosis medications (11 of bisphosphonates, four of selective estrogen receptor modulators, three of anabolic medications, two of hormone replacement therapy, and one each of odanacatib, denosumab, and romosozumab).
• Overall, 43% of the included 123,164 patients were aged 70 years or older.
• The main outcomes were fractures and bone mineral density.

TAKEAWAY:

• There was a similar benefit regardless of age when it came to the reduction in risks for hip fracture (odds ratio, 0.65 vs 0.72; P for interaction = .50) and any fracture (odds ratio, 0.72 vs 0.70; P for interaction = .20).
• Findings were comparable in analyses restricted to bisphosphonate trials, except that the reduction in hip fracture risk was greater among the younger group (hazard ratio, 0.44 vs 0.79; P for interaction = .02).
• The benefit of anti-osteoporosis medication in increasing hip and spine bone mineral density at 24 months was significantly greater among the older patients.

IN PRACTICE:

Taken together, the study results “strongly support treatment in those over age 70,” the authors wrote. “These are important findings with potential impact in patient treatment since it goes against a common misconception that medications are less effective in older people,” they added.

SOURCE:

The study was led by Marian Schini, MD, PhD, FHEA, University of Sheffield, England, and was published online in the Journal of Bone and Mineral Research.

LIMITATIONS:

Limitations included a preponderance of female patients (99%), possible residual confounding, a lack of analysis of adverse effects, and potentially different findings using alternate age cutoffs.

DISCLOSURES:

The study was funded by the American Society for Bone Mineral Research. Some authors disclosed affiliations with companies that manufacture anti-osteoporosis drugs.

A version of this article appeared on Medscape.com.

TOPLINE:

Anti-osteoporosis medications reduce fracture risk similarly, regardless of whether patients are younger or older than 70 years.

METHODOLOGY:

• Investigators conducted the study as part of a  to assess bone mineral density as a surrogate marker for fracture risk.
• Analyses used individual patient data from 23 randomized placebo-controlled trials of anti-osteoporosis medications (11 of bisphosphonates, four of selective estrogen receptor modulators, three of anabolic medications, two of hormone replacement therapy, and one each of odanacatib, denosumab, and romosozumab).
• Overall, 43% of the included 123,164 patients were aged 70 years or older.
• The main outcomes were fractures and bone mineral density.

TAKEAWAY:

• There was a similar benefit regardless of age when it came to the reduction in risks for hip fracture (odds ratio, 0.65 vs 0.72; P for interaction = .50) and any fracture (odds ratio, 0.72 vs 0.70; P for interaction = .20).
• Findings were comparable in analyses restricted to bisphosphonate trials, except that the reduction in hip fracture risk was greater among the younger group (hazard ratio, 0.44 vs 0.79; P for interaction = .02).
• The benefit of anti-osteoporosis medication in increasing hip and spine bone mineral density at 24 months was significantly greater among the older patients.

IN PRACTICE:

Taken together, the study results “strongly support treatment in those over age 70,” the authors wrote. “These are important findings with potential impact in patient treatment since it goes against a common misconception that medications are less effective in older people,” they added.

SOURCE:

The study was led by Marian Schini, MD, PhD, FHEA, University of Sheffield, England, and was published online in the Journal of Bone and Mineral Research.

LIMITATIONS:

Limitations included a preponderance of female patients (99%), possible residual confounding, a lack of analysis of adverse effects, and potentially different findings using alternate age cutoffs.

DISCLOSURES:

The study was funded by the American Society for Bone Mineral Research. Some authors disclosed affiliations with companies that manufacture anti-osteoporosis drugs.

A version of this article appeared on Medscape.com.

TOPLINE:

Anti-osteoporosis medications reduce fracture risk similarly, regardless of whether patients are younger or older than 70 years.

METHODOLOGY:

• Investigators conducted the study as part of a  to assess bone mineral density as a surrogate marker for fracture risk.
• Analyses used individual patient data from 23 randomized placebo-controlled trials of anti-osteoporosis medications (11 of bisphosphonates, four of selective estrogen receptor modulators, three of anabolic medications, two of hormone replacement therapy, and one each of odanacatib, denosumab, and romosozumab).
• Overall, 43% of the included 123,164 patients were aged 70 years or older.
• The main outcomes were fractures and bone mineral density.

TAKEAWAY:

• There was a similar benefit regardless of age when it came to the reduction in risks for hip fracture (odds ratio, 0.65 vs 0.72; P for interaction = .50) and any fracture (odds ratio, 0.72 vs 0.70; P for interaction = .20).
• Findings were comparable in analyses restricted to bisphosphonate trials, except that the reduction in hip fracture risk was greater among the younger group (hazard ratio, 0.44 vs 0.79; P for interaction = .02).
• The benefit of anti-osteoporosis medication in increasing hip and spine bone mineral density at 24 months was significantly greater among the older patients.

IN PRACTICE:

Taken together, the study results “strongly support treatment in those over age 70,” the authors wrote. “These are important findings with potential impact in patient treatment since it goes against a common misconception that medications are less effective in older people,” they added.

SOURCE:

The study was led by Marian Schini, MD, PhD, FHEA, University of Sheffield, England, and was published online in the Journal of Bone and Mineral Research.

LIMITATIONS:

Limitations included a preponderance of female patients (99%), possible residual confounding, a lack of analysis of adverse effects, and potentially different findings using alternate age cutoffs.

DISCLOSURES:

The study was funded by the American Society for Bone Mineral Research. Some authors disclosed affiliations with companies that manufacture anti-osteoporosis drugs.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of supervised exercise to obesity pharmacotherapy has shown greater potential for maintaining weight loss and improving body composition after treatment termination than pharmacotherapy alone.

METHODOLOGY:

• Despite significant weight loss achieved with incretin-based obesity pharmacotherapies, their high costs and gastrointestinal adverse events lead to high discontinuation rates with subsequent regaining of weight and body fat.
• Researchers investigated if a strategy involving both exercise and , a -like peptide-1 receptor agonist, was better than either intervention alone in terms of maintaining weight loss and body composition after treatment termination.
• They conducted a 1-year posttreatment analysis of the S-LiTE study, including 109 adults with obesity (age, 18-65 years; body mass index, 32-43) who completed an 8-week low-calorie diet resulting in ≥ 5% weight loss.
• Participants were then randomly allocated to a 52-week weight loss maintenance intervention with either liraglutide or placebo alone or liraglutide or placebo plus supervised exercise.
• The primary outcome was the change in body weight (kg) from randomization to 1 year after the termination of weight maintenance intervention (0-104 weeks), and the secondary outcome was the change in body-fat percentage from 0 to 104 weeks.

TAKEAWAY:

• From week 0 to week 104, supervised exercise plus liraglutide led to 5.1 kg lower weight gain (P = .040) and a 2.3%-point greater decrease in body-fat percentage (P = .026) than liraglutide alone.
• During the 1 year after treatment termination (52-104 weeks), those in the liraglutide group regained 6 kg (95% CI, 2.1-10.0) more than those who were in the supervised exercise plus placebo group, and 2.5 kg (95% CI, -1.5 to 6.5) more than those who received supervised exercise plus liraglutide.
• After 1 year of treatment termination (week 104), the supervised exercise plus liraglutide group had significantly higher odds of maintaining a weight loss of ≥ 10% of initial body weight than the liraglutide (odds ratio [OR], 4.2; 95% CI, 1.6-10.8) or placebo (OR, 7.2; 95% CI, 2.4-21.3) groups.
• The combination of exercise and liraglutide also improved physical functioning along with energy and fatigue scores.

IN PRACTICE:

“Future lifestyle-based treatments during obesity pharmacotherapy may further improve body weight and composition outcomes, with an additional focus on strategies and tools to maintain healthy physical activity habits after termination of pharmacotherapy,” the researchers wrote.

SOURCE:

This study, with lead author Simon Birk Kjær Jensen, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, was published online in eClinicalMedicine.

LIMITATIONS:

Fewer participants from the placebo group took part in this posttreatment study. Across all treatment groups, participants who attended the posttreatment study had a better mean treatment response during the active treatment than those who did not attend.

DISCLOSURES:

The study was funded by the Novo Nordisk Foundation and Helsefonden. Some authors declared participating in advisory boards and receiving research grants and lecture fees from various sources including Novo Nordisk.

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

TOPLINE:

The addition of supervised exercise to obesity pharmacotherapy has shown greater potential for maintaining weight loss and improving body composition after treatment termination than pharmacotherapy alone.

METHODOLOGY:

• Despite significant weight loss achieved with incretin-based obesity pharmacotherapies, their high costs and gastrointestinal adverse events lead to high discontinuation rates with subsequent regaining of weight and body fat.
• Researchers investigated if a strategy involving both exercise and , a -like peptide-1 receptor agonist, was better than either intervention alone in terms of maintaining weight loss and body composition after treatment termination.
• They conducted a 1-year posttreatment analysis of the S-LiTE study, including 109 adults with obesity (age, 18-65 years; body mass index, 32-43) who completed an 8-week low-calorie diet resulting in ≥ 5% weight loss.
• Participants were then randomly allocated to a 52-week weight loss maintenance intervention with either liraglutide or placebo alone or liraglutide or placebo plus supervised exercise.
• The primary outcome was the change in body weight (kg) from randomization to 1 year after the termination of weight maintenance intervention (0-104 weeks), and the secondary outcome was the change in body-fat percentage from 0 to 104 weeks.

TAKEAWAY:

• From week 0 to week 104, supervised exercise plus liraglutide led to 5.1 kg lower weight gain (P = .040) and a 2.3%-point greater decrease in body-fat percentage (P = .026) than liraglutide alone.
• During the 1 year after treatment termination (52-104 weeks), those in the liraglutide group regained 6 kg (95% CI, 2.1-10.0) more than those who were in the supervised exercise plus placebo group, and 2.5 kg (95% CI, -1.5 to 6.5) more than those who received supervised exercise plus liraglutide.
• After 1 year of treatment termination (week 104), the supervised exercise plus liraglutide group had significantly higher odds of maintaining a weight loss of ≥ 10% of initial body weight than the liraglutide (odds ratio [OR], 4.2; 95% CI, 1.6-10.8) or placebo (OR, 7.2; 95% CI, 2.4-21.3) groups.
• The combination of exercise and liraglutide also improved physical functioning along with energy and fatigue scores.

IN PRACTICE:

“Future lifestyle-based treatments during obesity pharmacotherapy may further improve body weight and composition outcomes, with an additional focus on strategies and tools to maintain healthy physical activity habits after termination of pharmacotherapy,” the researchers wrote.

SOURCE:

This study, with lead author Simon Birk Kjær Jensen, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, was published online in eClinicalMedicine.

LIMITATIONS:

Fewer participants from the placebo group took part in this posttreatment study. Across all treatment groups, participants who attended the posttreatment study had a better mean treatment response during the active treatment than those who did not attend.

DISCLOSURES:

The study was funded by the Novo Nordisk Foundation and Helsefonden. Some authors declared participating in advisory boards and receiving research grants and lecture fees from various sources including Novo Nordisk.

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

TOPLINE:

The addition of supervised exercise to obesity pharmacotherapy has shown greater potential for maintaining weight loss and improving body composition after treatment termination than pharmacotherapy alone.

METHODOLOGY:

• Despite significant weight loss achieved with incretin-based obesity pharmacotherapies, their high costs and gastrointestinal adverse events lead to high discontinuation rates with subsequent regaining of weight and body fat.
• Researchers investigated if a strategy involving both exercise and , a -like peptide-1 receptor agonist, was better than either intervention alone in terms of maintaining weight loss and body composition after treatment termination.
• They conducted a 1-year posttreatment analysis of the S-LiTE study, including 109 adults with obesity (age, 18-65 years; body mass index, 32-43) who completed an 8-week low-calorie diet resulting in ≥ 5% weight loss.
• Participants were then randomly allocated to a 52-week weight loss maintenance intervention with either liraglutide or placebo alone or liraglutide or placebo plus supervised exercise.
• The primary outcome was the change in body weight (kg) from randomization to 1 year after the termination of weight maintenance intervention (0-104 weeks), and the secondary outcome was the change in body-fat percentage from 0 to 104 weeks.

TAKEAWAY:

• From week 0 to week 104, supervised exercise plus liraglutide led to 5.1 kg lower weight gain (P = .040) and a 2.3%-point greater decrease in body-fat percentage (P = .026) than liraglutide alone.
• During the 1 year after treatment termination (52-104 weeks), those in the liraglutide group regained 6 kg (95% CI, 2.1-10.0) more than those who were in the supervised exercise plus placebo group, and 2.5 kg (95% CI, -1.5 to 6.5) more than those who received supervised exercise plus liraglutide.
• After 1 year of treatment termination (week 104), the supervised exercise plus liraglutide group had significantly higher odds of maintaining a weight loss of ≥ 10% of initial body weight than the liraglutide (odds ratio [OR], 4.2; 95% CI, 1.6-10.8) or placebo (OR, 7.2; 95% CI, 2.4-21.3) groups.
• The combination of exercise and liraglutide also improved physical functioning along with energy and fatigue scores.

IN PRACTICE:

“Future lifestyle-based treatments during obesity pharmacotherapy may further improve body weight and composition outcomes, with an additional focus on strategies and tools to maintain healthy physical activity habits after termination of pharmacotherapy,” the researchers wrote.

SOURCE:

This study, with lead author Simon Birk Kjær Jensen, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, was published online in eClinicalMedicine.

LIMITATIONS:

Fewer participants from the placebo group took part in this posttreatment study. Across all treatment groups, participants who attended the posttreatment study had a better mean treatment response during the active treatment than those who did not attend.

DISCLOSURES:

The study was funded by the Novo Nordisk Foundation and Helsefonden. Some authors declared participating in advisory boards and receiving research grants and lecture fees from various sources including Novo Nordisk.

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

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin D deficiency is independently linked to the risk for diabetic peripheral neuropathy (DPN) by potentially affecting large nerve fibers in older patients with type 2 diabetes (T2D).

METHODOLOGY:

• Although previous research has shown that vitamin D deficiency is common in patients with diabetes and may increase the risk for peripheral neuropathy, its effects on large and small nerve fiber lesions have not been well explored yet.
• Researchers conducted a cross-sectional study to understand the association between vitamin D deficiency and DPN development in 230 older patients (mean age, 67 years) with T2D for about 15 years who were recruited from Beijing Hospital between 2020 and 2023.
• All patients were evaluated for DPN based on poor blood sugar control or symptoms such as pain and sensory abnormalities, of which 175 patients diagnosed with DPN were propensity-matched with 55 patients without DPN.
• Vitamin D deficiency, defined as serum 25-hydroxyvitamin D circulating levels below 20 ng/mL, was reported in 169 patients.
• Large nerve fiber lesions were evaluated using electromyography, and small nerve fiber lesions were assessed by measuring skin conductance.

TAKEAWAY:

• Vitamin D deficiency was more likely to affect large fiber lesions, suggested by longer median sensory nerve latency, minimum latency of the F-wave, and median nerve motor evoked potential latency than those in the vitamin D–sufficient group.
• Furthermore, vitamin D deficiency was linked to large fiber neuropathy with increased odds of prolongation of motor nerve latency (odds ratio, 1.362; P = .038).
• The electrochemical skin conductance, which indicates damage to small nerve fibers, was comparable between patients with and without vitamin D deficiency.

IN PRACTICE:

This study is too preliminary to have practice application.

SOURCE:

This study was led by Sijia Fei, Department of Endocrinology, Beijing Hospital, Beijing, People’s Republic of China, and was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

Skin biopsy, the “gold-standard” for quantifying intraepidermal nerve fiber density, was not used to assess small nerve fiber lesions. Additionally, a causal link between vitamin D deficiency and diabetic nerve damage was not established owing to the cross-sectional nature of the study. Some patients with T2D may have been receiving insulin therapy, which may have affected vitamin D levels.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China and China National Key R&D Program. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin D deficiency is independently linked to the risk for diabetic peripheral neuropathy (DPN) by potentially affecting large nerve fibers in older patients with type 2 diabetes (T2D).

METHODOLOGY:

• Although previous research has shown that vitamin D deficiency is common in patients with diabetes and may increase the risk for peripheral neuropathy, its effects on large and small nerve fiber lesions have not been well explored yet.
• Researchers conducted a cross-sectional study to understand the association between vitamin D deficiency and DPN development in 230 older patients (mean age, 67 years) with T2D for about 15 years who were recruited from Beijing Hospital between 2020 and 2023.
• All patients were evaluated for DPN based on poor blood sugar control or symptoms such as pain and sensory abnormalities, of which 175 patients diagnosed with DPN were propensity-matched with 55 patients without DPN.
• Vitamin D deficiency, defined as serum 25-hydroxyvitamin D circulating levels below 20 ng/mL, was reported in 169 patients.
• Large nerve fiber lesions were evaluated using electromyography, and small nerve fiber lesions were assessed by measuring skin conductance.

TAKEAWAY:

• Vitamin D deficiency was more likely to affect large fiber lesions, suggested by longer median sensory nerve latency, minimum latency of the F-wave, and median nerve motor evoked potential latency than those in the vitamin D–sufficient group.
• Furthermore, vitamin D deficiency was linked to large fiber neuropathy with increased odds of prolongation of motor nerve latency (odds ratio, 1.362; P = .038).
• The electrochemical skin conductance, which indicates damage to small nerve fibers, was comparable between patients with and without vitamin D deficiency.

IN PRACTICE:

This study is too preliminary to have practice application.

SOURCE:

This study was led by Sijia Fei, Department of Endocrinology, Beijing Hospital, Beijing, People’s Republic of China, and was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

Skin biopsy, the “gold-standard” for quantifying intraepidermal nerve fiber density, was not used to assess small nerve fiber lesions. Additionally, a causal link between vitamin D deficiency and diabetic nerve damage was not established owing to the cross-sectional nature of the study. Some patients with T2D may have been receiving insulin therapy, which may have affected vitamin D levels.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China and China National Key R&D Program. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin D deficiency is independently linked to the risk for diabetic peripheral neuropathy (DPN) by potentially affecting large nerve fibers in older patients with type 2 diabetes (T2D).

METHODOLOGY:

• Although previous research has shown that vitamin D deficiency is common in patients with diabetes and may increase the risk for peripheral neuropathy, its effects on large and small nerve fiber lesions have not been well explored yet.
• Researchers conducted a cross-sectional study to understand the association between vitamin D deficiency and DPN development in 230 older patients (mean age, 67 years) with T2D for about 15 years who were recruited from Beijing Hospital between 2020 and 2023.
• All patients were evaluated for DPN based on poor blood sugar control or symptoms such as pain and sensory abnormalities, of which 175 patients diagnosed with DPN were propensity-matched with 55 patients without DPN.
• Vitamin D deficiency, defined as serum 25-hydroxyvitamin D circulating levels below 20 ng/mL, was reported in 169 patients.
• Large nerve fiber lesions were evaluated using electromyography, and small nerve fiber lesions were assessed by measuring skin conductance.

TAKEAWAY:

• Vitamin D deficiency was more likely to affect large fiber lesions, suggested by longer median sensory nerve latency, minimum latency of the F-wave, and median nerve motor evoked potential latency than those in the vitamin D–sufficient group.
• Furthermore, vitamin D deficiency was linked to large fiber neuropathy with increased odds of prolongation of motor nerve latency (odds ratio, 1.362; P = .038).
• The electrochemical skin conductance, which indicates damage to small nerve fibers, was comparable between patients with and without vitamin D deficiency.

IN PRACTICE:

This study is too preliminary to have practice application.

SOURCE:

This study was led by Sijia Fei, Department of Endocrinology, Beijing Hospital, Beijing, People’s Republic of China, and was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

Skin biopsy, the “gold-standard” for quantifying intraepidermal nerve fiber density, was not used to assess small nerve fiber lesions. Additionally, a causal link between vitamin D deficiency and diabetic nerve damage was not established owing to the cross-sectional nature of the study. Some patients with T2D may have been receiving insulin therapy, which may have affected vitamin D levels.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China and China National Key R&D Program. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.