Marlene Busko

Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight, compared with placebo, report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
 

‘Extremely welcome tools for severe obesity’

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
 

Most patients had severe obesity, sleeve gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m² (57% had a BMI ≥ 40 kg/m²). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight, compared with placebo, report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
 

‘Extremely welcome tools for severe obesity’

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
 

Most patients had severe obesity, sleeve gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m² (57% had a BMI ≥ 40 kg/m²). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight, compared with placebo, report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
 

‘Extremely welcome tools for severe obesity’

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
 

Most patients had severe obesity, sleeve gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m² (57% had a BMI ≥ 40 kg/m²). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

SAN DIEGO – Survodutide, a dual glucagonlike peptide–1 (GLP-1) and glucagon receptor agonist, led to “striking” weight loss in a phase 2 dosing trial in people with overweight/obesity but without type 2 diabetes.

Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.

Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.

Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.

The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.

Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”

“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.

Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.

“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
 

Close to 400 patients, five doses, 46-week endpoint

The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m² (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.

On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m², and 68% were women.

They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).

The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.

Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.

In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.

Primary outcome was the percentage change in body weight from baseline to week 46.

Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.

Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.

Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.

That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.

In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.

Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.

There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.

These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
 

Survodutide has FDA fast track designation for NASH

Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.

The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.

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

SAN DIEGO – Survodutide, a dual glucagonlike peptide–1 (GLP-1) and glucagon receptor agonist, led to “striking” weight loss in a phase 2 dosing trial in people with overweight/obesity but without type 2 diabetes.

Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.

Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.

Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.

The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.

Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”

“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.

Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.

“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
 

Close to 400 patients, five doses, 46-week endpoint

The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m² (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.

On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m², and 68% were women.

They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).

The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.

Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.

In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.

Primary outcome was the percentage change in body weight from baseline to week 46.

Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.

Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.

Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.

That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.

In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.

Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.

There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.

These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
 

Survodutide has FDA fast track designation for NASH

Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.

The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.

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

SAN DIEGO – Survodutide, a dual glucagonlike peptide–1 (GLP-1) and glucagon receptor agonist, led to “striking” weight loss in a phase 2 dosing trial in people with overweight/obesity but without type 2 diabetes.

Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.

Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.

Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.

The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.

Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”

“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.

Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.

“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
 

Close to 400 patients, five doses, 46-week endpoint

The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m² (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.

On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m², and 68% were women.

They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).

The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.

Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.

In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.

Primary outcome was the percentage change in body weight from baseline to week 46.

Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.

Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.

Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.

That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.

In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.

Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.

There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.

These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
 

Survodutide has FDA fast track designation for NASH

Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.

The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.

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

SAN DIEGO – Coadministration of the long-acting amylin analog cagrilintide plus the glucagonlike peptide–1 (GLP-1) agonist semaglutide, dubbed CagriSema, resulted in significantly greater weight loss, along with improved measures of glucose control, than either agent alone, in a small, short phase 2 trial of patients with type 2 diabetes. 

Juan P. Frias, MD, presented the findings at the annual scientific sessions of the American Diabetes Association, which were simultaneously published in The Lancet.

“Overall, in this phase 2 trial in people with type 2 diabetes, clinically relevant improvements in glycemic control – as assessed by [hemoglobin] A1c, [time in range], and other [continuous glucose monitoring (CGM)] measures – were observed with CagriSema, as well as weight loss of a magnitude not previously reported with pharmacotherapies in this population. CagriSema also had an acceptable safety profile,” the researchers summarized.

“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 studies,” said Dr. Frias, from Velocity Clinical Research, Los Angeles.

In reply to audience questions, he said he was “pleasantly surprised” with the low gastrointestinal adverse events, which may have been related to the slower dosing titration. He also noted that patients in the study did not receive dietary counseling, unlike in the STEP-2 trial, where weight loss with semaglutide was greater than in this study.  

Time in normal blood glucose range in the CagriSema group went from 40% at baseline to 89% at week 32, Chantal Mathieu, MD, PhD, reported during a follow-up presentation that focused on the trial’s CGM findings.

“I was extremely happy that we were allowed to include CGM measurement because it does give you more information, especially in a short-term trial,” said Dr. Mathieu, from the Katholieke Universiteit Leuven (Belgium). The CGM data were collected for 10 days preceding baseline and at weeks 20 and 32.

“At this point in time, it is difficult to make a final determination” about potential future clinical applications, session chair Elisabetta Patorno, MD, DrPH, from Harvard Medical School, Boston, said in an interview. “This was a phase 2 randomized controlled trial, so more patients are needed.

“It’s very interesting what was found with the use of CGM, which makes us think whether they should always be part of [trials] versus the more traditional A1c assessment,” Dr. Patorno added.
 

‘Synergistic effect for both glycemic control and weight loss’

“CagriSema is the next in a series of gut hormone analogs with the potential to herald a new era in treating obesity and preventing diabesity,” the coexistence of type 2 diabetes and obesity, Caroline M. Apovian, MD, and Marie E. McDonnell, MD, both also from Harvard Medical School, wrote in an accompanying editorial in The Lancet.

Cagrilintide plus semaglutide each “effectively delay gastric emptying, suppress glucagon release, and are involved in the regulation of appetite and satiety in the brain,” they noted.

The results – a substantial difference in effect size between the combination drug and each component alone – show that “there is a synergistic effect for both glycemic control and weight loss.

“The weight loss seen in this phase 2 trial of CagriSema in 32 weeks could predict a phase 3 trial result over 1 year that might surpass that of semaglutide (14.9%) and tirzepatide (20.9%) in a population without type 2 diabetes, and might equal that of bariatric surgery (23.5%-30.4%),” they speculated.

However, it’s still early days, the editorialists cautioned. Study limitations include that it was a small trial and the mean duration of type 2 diabetes at baseline was shorter in the CagriSema group (6.4 years) than in the semaglutide or cagrilintide alone groups (9.2 years and 10.7 years, respectively).

The rate of gastrointestinal adverse events was also higher in the CagriSema group (58%) than in the other two groups (about 33%). However, the adverse events “were all mild or moderate and not severe enough to lead to participant withdrawal,” they noted. “Remarkably, only one participant, from the semaglutide group, withdrew due to adverse events during the 32-week trial across all groups.

“Although bariatric surgery remains the most effective treatment for severe obesity, offering the most robust weight reduction, remission of type 2 diabetes, and reduced cardiovascular mortality,” the study suggests that “combination metabolic hormonal therapy could offer all three of these outcomes in the near future,” Dr. Apovian and Dr. McDonnell wrote.
 

92 patients randomized to three treatments

In the study, researchers randomized 92 adults with type 2 diabetes and a body mass index of at least 27 kg/m² taking metformin alone (73%) or metformin plus a sodium-glucose cotransporter 2 inhibitor (27%), at 17 sites in the United States, between August and October 2021.

Patients were a mean age of 58 years and 64% were men. Mean A1c was 8.4% and mean bodyweight was 106 kg (234 lb).

They were randomized 1:1:1 to receive up to maximal once-weekly doses of 2.4 mg semaglutide and 2.4 mg cagrilintide (CagriSema, given in two injector pens), 2.4 mg semaglutide (plus placebo), or 2.4 mg cagrilintide (plus placebo).

Both cagrilintide and semaglutide are manufactured by the Danish company Novo Nordisk. Semaglutide is already approved in the United States for type 2 diabetes, as Ozempic, and as the weight-loss drug Wegovy. Cagrilintide is not yet approved.

Treatment doses were escalated every 4 weeks from 0.25 to 0.5 to 1.0 to 1.7 mg to a maintenance dose of 2.4 mg at 16 weeks. Patients then entered a 16-week maintenance phase followed by a 5-week follow-up period.

Among the key findings, the reduction in A1c at 32 weeks, compared with baseline (primary outcome), was –2.2% with CagriSema, –1.8% with semaglutide, and –0.9% with cagrilintide, but was not significantly greater with CagriSema versus semaglutide (–0.4%; P = .07).

However, in a secondary outcome, there was a significantly greater difference in A1c at 32 weeks with CagriSema versus cagrilintide (–1.3%; P < .0001). Moreover, 89% of patients in the CagriSema group reached an A1c less than 7%.

In other secondary outcomes, there was a significantly greater reduction in body weight at 32 weeks with CagriSema versus cagrilintide or semaglutide, with 71% of patients in the CagriSema group achieving greater than 10% reduction in body weight. Patients in the CagriSema group also had clinically relevant improvements in blood pressure, lipids, and high-sensitivity C-reactive protein.

Adverse events – reported in 68% of patients with CagriSema versus 71% with semaglutide and 80% with cagrilintide – were mostly mild or moderate gastrointestinal events, consistent with those seen in these two drug classes.

At week 32, time in range was 89% with CagriSema versus 76% with semaglutide and 72% with cagrilintide.

“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 agonist and an amylin analog in participants with type 2 diabetes,” the researchers summarize. “These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.”

This trial was sponsored by Novo Nordisk. Dr. Frias, Dr. Mathieu, Dr. Apovian, and Dr. McDonnell reported financial relationships with a number of companies.

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

SAN DIEGO – Coadministration of the long-acting amylin analog cagrilintide plus the glucagonlike peptide–1 (GLP-1) agonist semaglutide, dubbed CagriSema, resulted in significantly greater weight loss, along with improved measures of glucose control, than either agent alone, in a small, short phase 2 trial of patients with type 2 diabetes. 

Juan P. Frias, MD, presented the findings at the annual scientific sessions of the American Diabetes Association, which were simultaneously published in The Lancet.

“Overall, in this phase 2 trial in people with type 2 diabetes, clinically relevant improvements in glycemic control – as assessed by [hemoglobin] A1c, [time in range], and other [continuous glucose monitoring (CGM)] measures – were observed with CagriSema, as well as weight loss of a magnitude not previously reported with pharmacotherapies in this population. CagriSema also had an acceptable safety profile,” the researchers summarized.

“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 studies,” said Dr. Frias, from Velocity Clinical Research, Los Angeles.

In reply to audience questions, he said he was “pleasantly surprised” with the low gastrointestinal adverse events, which may have been related to the slower dosing titration. He also noted that patients in the study did not receive dietary counseling, unlike in the STEP-2 trial, where weight loss with semaglutide was greater than in this study.  

Time in normal blood glucose range in the CagriSema group went from 40% at baseline to 89% at week 32, Chantal Mathieu, MD, PhD, reported during a follow-up presentation that focused on the trial’s CGM findings.

“I was extremely happy that we were allowed to include CGM measurement because it does give you more information, especially in a short-term trial,” said Dr. Mathieu, from the Katholieke Universiteit Leuven (Belgium). The CGM data were collected for 10 days preceding baseline and at weeks 20 and 32.

“At this point in time, it is difficult to make a final determination” about potential future clinical applications, session chair Elisabetta Patorno, MD, DrPH, from Harvard Medical School, Boston, said in an interview. “This was a phase 2 randomized controlled trial, so more patients are needed.

“It’s very interesting what was found with the use of CGM, which makes us think whether they should always be part of [trials] versus the more traditional A1c assessment,” Dr. Patorno added.
 

‘Synergistic effect for both glycemic control and weight loss’

“CagriSema is the next in a series of gut hormone analogs with the potential to herald a new era in treating obesity and preventing diabesity,” the coexistence of type 2 diabetes and obesity, Caroline M. Apovian, MD, and Marie E. McDonnell, MD, both also from Harvard Medical School, wrote in an accompanying editorial in The Lancet.

Cagrilintide plus semaglutide each “effectively delay gastric emptying, suppress glucagon release, and are involved in the regulation of appetite and satiety in the brain,” they noted.

The results – a substantial difference in effect size between the combination drug and each component alone – show that “there is a synergistic effect for both glycemic control and weight loss.

“The weight loss seen in this phase 2 trial of CagriSema in 32 weeks could predict a phase 3 trial result over 1 year that might surpass that of semaglutide (14.9%) and tirzepatide (20.9%) in a population without type 2 diabetes, and might equal that of bariatric surgery (23.5%-30.4%),” they speculated.

However, it’s still early days, the editorialists cautioned. Study limitations include that it was a small trial and the mean duration of type 2 diabetes at baseline was shorter in the CagriSema group (6.4 years) than in the semaglutide or cagrilintide alone groups (9.2 years and 10.7 years, respectively).

The rate of gastrointestinal adverse events was also higher in the CagriSema group (58%) than in the other two groups (about 33%). However, the adverse events “were all mild or moderate and not severe enough to lead to participant withdrawal,” they noted. “Remarkably, only one participant, from the semaglutide group, withdrew due to adverse events during the 32-week trial across all groups.

“Although bariatric surgery remains the most effective treatment for severe obesity, offering the most robust weight reduction, remission of type 2 diabetes, and reduced cardiovascular mortality,” the study suggests that “combination metabolic hormonal therapy could offer all three of these outcomes in the near future,” Dr. Apovian and Dr. McDonnell wrote.
 

92 patients randomized to three treatments

In the study, researchers randomized 92 adults with type 2 diabetes and a body mass index of at least 27 kg/m² taking metformin alone (73%) or metformin plus a sodium-glucose cotransporter 2 inhibitor (27%), at 17 sites in the United States, between August and October 2021.

Patients were a mean age of 58 years and 64% were men. Mean A1c was 8.4% and mean bodyweight was 106 kg (234 lb).

They were randomized 1:1:1 to receive up to maximal once-weekly doses of 2.4 mg semaglutide and 2.4 mg cagrilintide (CagriSema, given in two injector pens), 2.4 mg semaglutide (plus placebo), or 2.4 mg cagrilintide (plus placebo).

Both cagrilintide and semaglutide are manufactured by the Danish company Novo Nordisk. Semaglutide is already approved in the United States for type 2 diabetes, as Ozempic, and as the weight-loss drug Wegovy. Cagrilintide is not yet approved.

Treatment doses were escalated every 4 weeks from 0.25 to 0.5 to 1.0 to 1.7 mg to a maintenance dose of 2.4 mg at 16 weeks. Patients then entered a 16-week maintenance phase followed by a 5-week follow-up period.

Among the key findings, the reduction in A1c at 32 weeks, compared with baseline (primary outcome), was –2.2% with CagriSema, –1.8% with semaglutide, and –0.9% with cagrilintide, but was not significantly greater with CagriSema versus semaglutide (–0.4%; P = .07).

However, in a secondary outcome, there was a significantly greater difference in A1c at 32 weeks with CagriSema versus cagrilintide (–1.3%; P < .0001). Moreover, 89% of patients in the CagriSema group reached an A1c less than 7%.

In other secondary outcomes, there was a significantly greater reduction in body weight at 32 weeks with CagriSema versus cagrilintide or semaglutide, with 71% of patients in the CagriSema group achieving greater than 10% reduction in body weight. Patients in the CagriSema group also had clinically relevant improvements in blood pressure, lipids, and high-sensitivity C-reactive protein.

Adverse events – reported in 68% of patients with CagriSema versus 71% with semaglutide and 80% with cagrilintide – were mostly mild or moderate gastrointestinal events, consistent with those seen in these two drug classes.

At week 32, time in range was 89% with CagriSema versus 76% with semaglutide and 72% with cagrilintide.

“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 agonist and an amylin analog in participants with type 2 diabetes,” the researchers summarize. “These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.”

This trial was sponsored by Novo Nordisk. Dr. Frias, Dr. Mathieu, Dr. Apovian, and Dr. McDonnell reported financial relationships with a number of companies.

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

SAN DIEGO – Coadministration of the long-acting amylin analog cagrilintide plus the glucagonlike peptide–1 (GLP-1) agonist semaglutide, dubbed CagriSema, resulted in significantly greater weight loss, along with improved measures of glucose control, than either agent alone, in a small, short phase 2 trial of patients with type 2 diabetes. 

Juan P. Frias, MD, presented the findings at the annual scientific sessions of the American Diabetes Association, which were simultaneously published in The Lancet.

“Overall, in this phase 2 trial in people with type 2 diabetes, clinically relevant improvements in glycemic control – as assessed by [hemoglobin] A1c, [time in range], and other [continuous glucose monitoring (CGM)] measures – were observed with CagriSema, as well as weight loss of a magnitude not previously reported with pharmacotherapies in this population. CagriSema also had an acceptable safety profile,” the researchers summarized.

“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 studies,” said Dr. Frias, from Velocity Clinical Research, Los Angeles.

In reply to audience questions, he said he was “pleasantly surprised” with the low gastrointestinal adverse events, which may have been related to the slower dosing titration. He also noted that patients in the study did not receive dietary counseling, unlike in the STEP-2 trial, where weight loss with semaglutide was greater than in this study.  

Time in normal blood glucose range in the CagriSema group went from 40% at baseline to 89% at week 32, Chantal Mathieu, MD, PhD, reported during a follow-up presentation that focused on the trial’s CGM findings.

“I was extremely happy that we were allowed to include CGM measurement because it does give you more information, especially in a short-term trial,” said Dr. Mathieu, from the Katholieke Universiteit Leuven (Belgium). The CGM data were collected for 10 days preceding baseline and at weeks 20 and 32.

“At this point in time, it is difficult to make a final determination” about potential future clinical applications, session chair Elisabetta Patorno, MD, DrPH, from Harvard Medical School, Boston, said in an interview. “This was a phase 2 randomized controlled trial, so more patients are needed.

“It’s very interesting what was found with the use of CGM, which makes us think whether they should always be part of [trials] versus the more traditional A1c assessment,” Dr. Patorno added.
 

‘Synergistic effect for both glycemic control and weight loss’

“CagriSema is the next in a series of gut hormone analogs with the potential to herald a new era in treating obesity and preventing diabesity,” the coexistence of type 2 diabetes and obesity, Caroline M. Apovian, MD, and Marie E. McDonnell, MD, both also from Harvard Medical School, wrote in an accompanying editorial in The Lancet.

Cagrilintide plus semaglutide each “effectively delay gastric emptying, suppress glucagon release, and are involved in the regulation of appetite and satiety in the brain,” they noted.

The results – a substantial difference in effect size between the combination drug and each component alone – show that “there is a synergistic effect for both glycemic control and weight loss.

“The weight loss seen in this phase 2 trial of CagriSema in 32 weeks could predict a phase 3 trial result over 1 year that might surpass that of semaglutide (14.9%) and tirzepatide (20.9%) in a population without type 2 diabetes, and might equal that of bariatric surgery (23.5%-30.4%),” they speculated.

However, it’s still early days, the editorialists cautioned. Study limitations include that it was a small trial and the mean duration of type 2 diabetes at baseline was shorter in the CagriSema group (6.4 years) than in the semaglutide or cagrilintide alone groups (9.2 years and 10.7 years, respectively).

The rate of gastrointestinal adverse events was also higher in the CagriSema group (58%) than in the other two groups (about 33%). However, the adverse events “were all mild or moderate and not severe enough to lead to participant withdrawal,” they noted. “Remarkably, only one participant, from the semaglutide group, withdrew due to adverse events during the 32-week trial across all groups.

“Although bariatric surgery remains the most effective treatment for severe obesity, offering the most robust weight reduction, remission of type 2 diabetes, and reduced cardiovascular mortality,” the study suggests that “combination metabolic hormonal therapy could offer all three of these outcomes in the near future,” Dr. Apovian and Dr. McDonnell wrote.
 

92 patients randomized to three treatments

In the study, researchers randomized 92 adults with type 2 diabetes and a body mass index of at least 27 kg/m² taking metformin alone (73%) or metformin plus a sodium-glucose cotransporter 2 inhibitor (27%), at 17 sites in the United States, between August and October 2021.

Patients were a mean age of 58 years and 64% were men. Mean A1c was 8.4% and mean bodyweight was 106 kg (234 lb).

They were randomized 1:1:1 to receive up to maximal once-weekly doses of 2.4 mg semaglutide and 2.4 mg cagrilintide (CagriSema, given in two injector pens), 2.4 mg semaglutide (plus placebo), or 2.4 mg cagrilintide (plus placebo).

Both cagrilintide and semaglutide are manufactured by the Danish company Novo Nordisk. Semaglutide is already approved in the United States for type 2 diabetes, as Ozempic, and as the weight-loss drug Wegovy. Cagrilintide is not yet approved.

Treatment doses were escalated every 4 weeks from 0.25 to 0.5 to 1.0 to 1.7 mg to a maintenance dose of 2.4 mg at 16 weeks. Patients then entered a 16-week maintenance phase followed by a 5-week follow-up period.

Among the key findings, the reduction in A1c at 32 weeks, compared with baseline (primary outcome), was –2.2% with CagriSema, –1.8% with semaglutide, and –0.9% with cagrilintide, but was not significantly greater with CagriSema versus semaglutide (–0.4%; P = .07).

However, in a secondary outcome, there was a significantly greater difference in A1c at 32 weeks with CagriSema versus cagrilintide (–1.3%; P < .0001). Moreover, 89% of patients in the CagriSema group reached an A1c less than 7%.

In other secondary outcomes, there was a significantly greater reduction in body weight at 32 weeks with CagriSema versus cagrilintide or semaglutide, with 71% of patients in the CagriSema group achieving greater than 10% reduction in body weight. Patients in the CagriSema group also had clinically relevant improvements in blood pressure, lipids, and high-sensitivity C-reactive protein.

Adverse events – reported in 68% of patients with CagriSema versus 71% with semaglutide and 80% with cagrilintide – were mostly mild or moderate gastrointestinal events, consistent with those seen in these two drug classes.

At week 32, time in range was 89% with CagriSema versus 76% with semaglutide and 72% with cagrilintide.

“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 agonist and an amylin analog in participants with type 2 diabetes,” the researchers summarize. “These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.”

This trial was sponsored by Novo Nordisk. Dr. Frias, Dr. Mathieu, Dr. Apovian, and Dr. McDonnell reported financial relationships with a number of companies.

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

Higher doses of oral semaglutide than the 14-mg/day dose that is currently approved for type 2 diabetes may be additional options for patients with prediabetes or diabetes and obesity, according to the results of two new phase 3 clinical trials.

The two trials, OASIS in patients with overweight or obesity without diabetes and PIONEER PLUS in patients with inadequately controlled type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in The Lancet.

Filip K. Knop, MD, PhD, University of Copenhagen, presented highlights of the OASIS-1 results, and Vanita R. Aroda, MD, Brigham and Women’s Hospital and Harvard University, Boston, presented key findings of PIONEER PLUS, during a press briefing prior to the ADA session.

OASIS-1 showed that “oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Dr. Knop summarized.

And “the PIONEER PLUS trial showed superior glycemic control and body-weight loss and improvement in cardiometabolic risk factors, with higher doses of once-daily oral semaglutide (25 mg and 50 mg) compared with the currently [highest] approved 14-mg dose,” said Dr. Aroda.

Session chair Marion Pragnell, PhD, vice president of research & science at ADA, said in an interview there is a need for multiple treatment options, as different patients respond differently to individual drugs. The oral dose of semaglutide has to be higher than that approved for subcutaneous injection (as Ozempic or Wegovy) because of bioavailability, but small-molecule research is advancing such that in future lower doses of oral drugs may have the same effect as the current lower subcutaneous doses of the drug.

The oral version of semaglutide (Rybelsus) was approved in the United States for type 2 diabetes in doses of 7 mg or 14 mg per day in 2019; it has not been approved for use in obesity.

Dr. Knop remarked that, in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide and the rest prefer weekly injected semaglutide.

“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” he added.

Participants in OASIS and PIONEER PLUS were instructed to take the once-daily study drug tablet in the morning, in the fasting state, with up to half a glass of water (120 mL) at least 30 minutes before intake of any other food, beverage, or oral medication.
 

OASIS: 50-mg daily pill in adults with overweight or obesity

OASIS is, to their knowledge, “the first trial to assess the bodyweight-lowering effect of an oral GLP-1 agonist (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” Dr. Knop and colleagues wrote.

The 50-mg dose induced clinically meaningful reductions in bodyweight, with accompanying improvements in cardiometabolic risk factors, consistent with results reported for subcutaneous semaglutide 2.4 mg once weekly (Wegovy) in a similar population.

As an adjunct to diet and physical activity, oral semaglutide 50 mg led to a mean bodyweight reduction of 15.1%, compared with 2.4% in the placebo group, and greater percentages of participants reaching bodyweight reduction targets of at least 5%, 10%, 15%, and 20%.

Body-weight reductions were accompanied by significant improvements in cardiometabolic risk factors, compared with placebo.

“These results indicate that oral semaglutide 50 mg could provide an effective, future option for people with overweight or obesity who would benefit from a GLP-1 receptor agonist,” they concluded.
 

PIONEER PLUS: Inadequately controlled type 2 diabetes

Reporting the PIONEER PLUS data, Dr. Aroda and colleagues said: “For people with inadequately controlled type 2 diabetes on a stable dose of one to three oral glucose-lowering drugs, higher doses (25 mg and 50 mg) of once-daily oral semaglutide provided more effective glycemic control and greater bodyweight loss than 14 mg semaglutide, without additional safety concerns.”

PIONEER PLUS is the first study to indicate that these bigger doses of semaglutide might provide a highly effective oral option to improve both glycemic control and weight loss in type 2 diabetes.

“This trial provides compelling evidence that the availability of a wider range of doses of oral semaglutide will allow for individualized dosing to the desired effect, and the ability to intensify treatment as needed,” said Dr. Aroda. “We are hopeful that these results encourage earlier effective management of type 2 diabetes and allow for broader management in the primary care setting.”

In an accompanying editorial Christina H. Sherrill, PharmD, and Andrew Y. Hwang, PharmD, write: “This expansion in dosing titration might provide clinicians with more opportunities to obtain the maximum efficacy of this oral GLP-1 agonist.”

But additional investigations “to establish whether the superior glycemic reduction seen at these higher doses translates into cardiovascular risk reduction” are needed, said Dr. Sherrill, of High Point (N.C.) University, and Dr. Hwang, of Massachusetts College of Pharmacy and Health Sciences University, Boston.

Such investigations “would further elucidate the place in therapy of high-dose oral semaglutide,” they concluded.

Dr. Aroda and colleagues agreed: “Future real-world studies will be needed to investigate the clinical impact of the availability of higher doses of oral semaglutide.”

The trials were funded by Novo Nordisk.

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

Higher doses of oral semaglutide than the 14-mg/day dose that is currently approved for type 2 diabetes may be additional options for patients with prediabetes or diabetes and obesity, according to the results of two new phase 3 clinical trials.

The two trials, OASIS in patients with overweight or obesity without diabetes and PIONEER PLUS in patients with inadequately controlled type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in The Lancet.

Filip K. Knop, MD, PhD, University of Copenhagen, presented highlights of the OASIS-1 results, and Vanita R. Aroda, MD, Brigham and Women’s Hospital and Harvard University, Boston, presented key findings of PIONEER PLUS, during a press briefing prior to the ADA session.

OASIS-1 showed that “oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Dr. Knop summarized.

And “the PIONEER PLUS trial showed superior glycemic control and body-weight loss and improvement in cardiometabolic risk factors, with higher doses of once-daily oral semaglutide (25 mg and 50 mg) compared with the currently [highest] approved 14-mg dose,” said Dr. Aroda.

Session chair Marion Pragnell, PhD, vice president of research & science at ADA, said in an interview there is a need for multiple treatment options, as different patients respond differently to individual drugs. The oral dose of semaglutide has to be higher than that approved for subcutaneous injection (as Ozempic or Wegovy) because of bioavailability, but small-molecule research is advancing such that in future lower doses of oral drugs may have the same effect as the current lower subcutaneous doses of the drug.

The oral version of semaglutide (Rybelsus) was approved in the United States for type 2 diabetes in doses of 7 mg or 14 mg per day in 2019; it has not been approved for use in obesity.

Dr. Knop remarked that, in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide and the rest prefer weekly injected semaglutide.

“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” he added.

Participants in OASIS and PIONEER PLUS were instructed to take the once-daily study drug tablet in the morning, in the fasting state, with up to half a glass of water (120 mL) at least 30 minutes before intake of any other food, beverage, or oral medication.
 

OASIS: 50-mg daily pill in adults with overweight or obesity

OASIS is, to their knowledge, “the first trial to assess the bodyweight-lowering effect of an oral GLP-1 agonist (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” Dr. Knop and colleagues wrote.

The 50-mg dose induced clinically meaningful reductions in bodyweight, with accompanying improvements in cardiometabolic risk factors, consistent with results reported for subcutaneous semaglutide 2.4 mg once weekly (Wegovy) in a similar population.

As an adjunct to diet and physical activity, oral semaglutide 50 mg led to a mean bodyweight reduction of 15.1%, compared with 2.4% in the placebo group, and greater percentages of participants reaching bodyweight reduction targets of at least 5%, 10%, 15%, and 20%.

Body-weight reductions were accompanied by significant improvements in cardiometabolic risk factors, compared with placebo.

“These results indicate that oral semaglutide 50 mg could provide an effective, future option for people with overweight or obesity who would benefit from a GLP-1 receptor agonist,” they concluded.
 

PIONEER PLUS: Inadequately controlled type 2 diabetes

Reporting the PIONEER PLUS data, Dr. Aroda and colleagues said: “For people with inadequately controlled type 2 diabetes on a stable dose of one to three oral glucose-lowering drugs, higher doses (25 mg and 50 mg) of once-daily oral semaglutide provided more effective glycemic control and greater bodyweight loss than 14 mg semaglutide, without additional safety concerns.”

PIONEER PLUS is the first study to indicate that these bigger doses of semaglutide might provide a highly effective oral option to improve both glycemic control and weight loss in type 2 diabetes.

“This trial provides compelling evidence that the availability of a wider range of doses of oral semaglutide will allow for individualized dosing to the desired effect, and the ability to intensify treatment as needed,” said Dr. Aroda. “We are hopeful that these results encourage earlier effective management of type 2 diabetes and allow for broader management in the primary care setting.”

In an accompanying editorial Christina H. Sherrill, PharmD, and Andrew Y. Hwang, PharmD, write: “This expansion in dosing titration might provide clinicians with more opportunities to obtain the maximum efficacy of this oral GLP-1 agonist.”

But additional investigations “to establish whether the superior glycemic reduction seen at these higher doses translates into cardiovascular risk reduction” are needed, said Dr. Sherrill, of High Point (N.C.) University, and Dr. Hwang, of Massachusetts College of Pharmacy and Health Sciences University, Boston.

Such investigations “would further elucidate the place in therapy of high-dose oral semaglutide,” they concluded.

Dr. Aroda and colleagues agreed: “Future real-world studies will be needed to investigate the clinical impact of the availability of higher doses of oral semaglutide.”

The trials were funded by Novo Nordisk.

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

Higher doses of oral semaglutide than the 14-mg/day dose that is currently approved for type 2 diabetes may be additional options for patients with prediabetes or diabetes and obesity, according to the results of two new phase 3 clinical trials.

The two trials, OASIS in patients with overweight or obesity without diabetes and PIONEER PLUS in patients with inadequately controlled type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in The Lancet.

Filip K. Knop, MD, PhD, University of Copenhagen, presented highlights of the OASIS-1 results, and Vanita R. Aroda, MD, Brigham and Women’s Hospital and Harvard University, Boston, presented key findings of PIONEER PLUS, during a press briefing prior to the ADA session.

OASIS-1 showed that “oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Dr. Knop summarized.

And “the PIONEER PLUS trial showed superior glycemic control and body-weight loss and improvement in cardiometabolic risk factors, with higher doses of once-daily oral semaglutide (25 mg and 50 mg) compared with the currently [highest] approved 14-mg dose,” said Dr. Aroda.

Session chair Marion Pragnell, PhD, vice president of research & science at ADA, said in an interview there is a need for multiple treatment options, as different patients respond differently to individual drugs. The oral dose of semaglutide has to be higher than that approved for subcutaneous injection (as Ozempic or Wegovy) because of bioavailability, but small-molecule research is advancing such that in future lower doses of oral drugs may have the same effect as the current lower subcutaneous doses of the drug.

The oral version of semaglutide (Rybelsus) was approved in the United States for type 2 diabetes in doses of 7 mg or 14 mg per day in 2019; it has not been approved for use in obesity.

Dr. Knop remarked that, in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide and the rest prefer weekly injected semaglutide.

“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” he added.

Participants in OASIS and PIONEER PLUS were instructed to take the once-daily study drug tablet in the morning, in the fasting state, with up to half a glass of water (120 mL) at least 30 minutes before intake of any other food, beverage, or oral medication.
 

OASIS: 50-mg daily pill in adults with overweight or obesity

OASIS is, to their knowledge, “the first trial to assess the bodyweight-lowering effect of an oral GLP-1 agonist (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” Dr. Knop and colleagues wrote.

The 50-mg dose induced clinically meaningful reductions in bodyweight, with accompanying improvements in cardiometabolic risk factors, consistent with results reported for subcutaneous semaglutide 2.4 mg once weekly (Wegovy) in a similar population.

As an adjunct to diet and physical activity, oral semaglutide 50 mg led to a mean bodyweight reduction of 15.1%, compared with 2.4% in the placebo group, and greater percentages of participants reaching bodyweight reduction targets of at least 5%, 10%, 15%, and 20%.

Body-weight reductions were accompanied by significant improvements in cardiometabolic risk factors, compared with placebo.

“These results indicate that oral semaglutide 50 mg could provide an effective, future option for people with overweight or obesity who would benefit from a GLP-1 receptor agonist,” they concluded.
 

PIONEER PLUS: Inadequately controlled type 2 diabetes

Reporting the PIONEER PLUS data, Dr. Aroda and colleagues said: “For people with inadequately controlled type 2 diabetes on a stable dose of one to three oral glucose-lowering drugs, higher doses (25 mg and 50 mg) of once-daily oral semaglutide provided more effective glycemic control and greater bodyweight loss than 14 mg semaglutide, without additional safety concerns.”

PIONEER PLUS is the first study to indicate that these bigger doses of semaglutide might provide a highly effective oral option to improve both glycemic control and weight loss in type 2 diabetes.

“This trial provides compelling evidence that the availability of a wider range of doses of oral semaglutide will allow for individualized dosing to the desired effect, and the ability to intensify treatment as needed,” said Dr. Aroda. “We are hopeful that these results encourage earlier effective management of type 2 diabetes and allow for broader management in the primary care setting.”

In an accompanying editorial Christina H. Sherrill, PharmD, and Andrew Y. Hwang, PharmD, write: “This expansion in dosing titration might provide clinicians with more opportunities to obtain the maximum efficacy of this oral GLP-1 agonist.”

But additional investigations “to establish whether the superior glycemic reduction seen at these higher doses translates into cardiovascular risk reduction” are needed, said Dr. Sherrill, of High Point (N.C.) University, and Dr. Hwang, of Massachusetts College of Pharmacy and Health Sciences University, Boston.

Such investigations “would further elucidate the place in therapy of high-dose oral semaglutide,” they concluded.

Dr. Aroda and colleagues agreed: “Future real-world studies will be needed to investigate the clinical impact of the availability of higher doses of oral semaglutide.”

The trials were funded by Novo Nordisk.

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

Interventions that specifically address diabetes distress can not only improve patient mental health but can also cut costs, according to two new studies in patients with type 1 diabetes presented at the annual scientific sessions of the American Diabetes Association.

Danielle Hessler Jones, PhD, presented findings from Behavioral Approaches to Reducing Diabetes Distress and Improving Glycemic Control (EMBARK) in adults with type 1 diabetes during an oral session.

The three-arm randomized trial found that patients had the greatest improvements in feelings of powerlessness after a 3-month behavioral intervention that combined type 1 diabetes education plus specific attention to diabetes distress.

And in a late-breaking poster, “Do The Right Thing: Behavioral Intervention for At-Risk T1D Youth,” David V. Wagner, PhD, showed that a behavioral intervention not only improved glycemic management but also reduced cost of care in disadvantaged youth.

“Diabetes distress is the emotional response to living with diabetes, the burden of relentless daily self-management, and the prospect of its long-term complications,” said Dr. Hessler Jones, professor and vice chair for research in the department of family and community medicine at the University of California, San Francisco.  

It is common, experienced by 20%-58% of people with type 1 and type 2 diabetes, and is different from depression, as it is associated with glycemic control and disease management. It “is also chronic and does not disappear on its own without intervention,” she stressed.

“It is the expected worries, concerns, and fears that are associated with struggling with a demanding and progressive chronic disease and its management,” she added.

The findings from EMBARK “suggest that distress reductions are greatest when interventions integrate education alongside approaches to address the emotional side of diabetes,” she said.  

The group is also analyzing changes in A1c with the three different interventions in EMBARK, with results expected this fall.

Dr. Hessler Jones said they also just received funding for DDASSIST, which will answer the question: “How do I translate this into care in my clinic?” The aim of the clinic training program is to bring the intervention to the diabetes care team.

“Could this program be delivered by somebody else, other than a psychologist?” an audience member asked. They will be looking at this, she replied.
 

‘Do the right thing’

For the late-breaking poster by Dr. Wagner and colleagues, researchers evaluated direct cost data from three health care systems provided for youth with type 1 diabetes who received an intensive behavioral health intervention, Novel Interventions in Children’s Healthcare (NICH).

Youths were included in the analyses if they had type 1 diabetes and at least 1 year of cost data prior to and following NICH enrollment. Outpatient, emergency department, and inpatient costs were combined. The analysis included 53 youth with the following characteristics: mean age, 14.2 years; 87% Medicaid; 58% female; 32% Black, 29% Non-Hispanic White, 28% Hispanic/Latinx, 7% Pacific Islander, 2% Asian, and 2% other racial and ethnic groups.

Average yearly costs significantly decreased from $20,400 per youth prior to NICH to $9,500 per youth afterward, largely due to inpatient charges.

“These results highlight the benefits of providing access to intensive interventions to pediatric populations experiencing health disparities,” said Dr. Wagner. “Investing early in the lives of youth experiencing health disparities is not only the right thing to do to improve patients’ health but it could also have a positive economic impact down the road.”
 

Three interventions in 300 adults with type 1 diabetes

Meanwhile, EMBARK recruited 300 patients with type 1 diabetes in the United States from clinics and community organizations who were aged 21 and older and had an elevated type 1 diabetes distress score (> 2.0) and A1c greater than or equal to 7.5%.

Participants were a mean age of 46 years, 79% were female, and 89% were White. They had a type 1 diabetes distress score of 2.8, a mean A1c of 8.3%, and 71% used an insulin pump and 79% used a continuous glucose monitor.

Participants were randomized to one of three interventions:

• Streamline: A traditional diabetes educator-led education and management program.
• Tuned-in: A psychologist-led program focused exclusively on reducing diabetes distress.
• Fixit: An integration of the two programs.

Interventions were given virtually over 3 months to small groups of 8-12 individuals and included initial workshops, one-to-one phone calls, and follow-up group meetings. Participants were then followed for 8 months.  

Researchers found statistically significant and substantial reductions in overall diabetes distress in all three interventions, with the greatest reductions in the combined intervention group, which were greater than in the educational approach alone group (P = .005).

The percentage of participants who no longer reported elevated diabetes distress at follow-up was 25% in Streamline, 37% in Tuned-in, and 42% in Fixit.

The percentage of participants who reported a minimal clinically important difference – the smallest change in a treatment outcome that an individual would identify as important – was also greatest in those in the Fixit intervention group (82%) than in the Tuned-in (74%) or Streamline (65%) interventions.
 

‘Adding the psychologist is where the real magic happens’

“The certified diabetes care specialist intervention is really a very standard thing that most clinicians would have access to; they tend to focus on knowledge and problem solving and some of the psychosocial issues,” Robert Gabbay, MD, PhD, chief scientific and medical officer for the ADA, said in an interview.

The EMBARK trial found a “graded response: CDCS alone, psychologist really focused on diabetes distress, and the two together, which would be the ideal practice model,” he noted.

There are these validated ways of measuring diabetes distress using a diabetes distress survey tool, which is also underutilized.  

“Adding the psychologist is really where the real magic happens in terms of diabetes distress,” Dr. Gabbay said.

“As you can imagine, [if] somebody ... feels powerless, it is going to be tough to manage their diabetes and unlikely to be terribly successful,” he observed. Often, these individuals are just not doing well. This study highlighted the importance of identifying this.

“I’m encouraged by the findings from the studies presented during this year’s Scientific Sessions as we continue to seek out innovative, evidence-based solutions that support people living with diabetes when they need it the most,” Dr. Gabbay concluded.

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

Interventions that specifically address diabetes distress can not only improve patient mental health but can also cut costs, according to two new studies in patients with type 1 diabetes presented at the annual scientific sessions of the American Diabetes Association.

Danielle Hessler Jones, PhD, presented findings from Behavioral Approaches to Reducing Diabetes Distress and Improving Glycemic Control (EMBARK) in adults with type 1 diabetes during an oral session.

The three-arm randomized trial found that patients had the greatest improvements in feelings of powerlessness after a 3-month behavioral intervention that combined type 1 diabetes education plus specific attention to diabetes distress.

And in a late-breaking poster, “Do The Right Thing: Behavioral Intervention for At-Risk T1D Youth,” David V. Wagner, PhD, showed that a behavioral intervention not only improved glycemic management but also reduced cost of care in disadvantaged youth.

“Diabetes distress is the emotional response to living with diabetes, the burden of relentless daily self-management, and the prospect of its long-term complications,” said Dr. Hessler Jones, professor and vice chair for research in the department of family and community medicine at the University of California, San Francisco.  

It is common, experienced by 20%-58% of people with type 1 and type 2 diabetes, and is different from depression, as it is associated with glycemic control and disease management. It “is also chronic and does not disappear on its own without intervention,” she stressed.

“It is the expected worries, concerns, and fears that are associated with struggling with a demanding and progressive chronic disease and its management,” she added.

The findings from EMBARK “suggest that distress reductions are greatest when interventions integrate education alongside approaches to address the emotional side of diabetes,” she said.  

The group is also analyzing changes in A1c with the three different interventions in EMBARK, with results expected this fall.

Dr. Hessler Jones said they also just received funding for DDASSIST, which will answer the question: “How do I translate this into care in my clinic?” The aim of the clinic training program is to bring the intervention to the diabetes care team.

“Could this program be delivered by somebody else, other than a psychologist?” an audience member asked. They will be looking at this, she replied.
 

‘Do the right thing’

For the late-breaking poster by Dr. Wagner and colleagues, researchers evaluated direct cost data from three health care systems provided for youth with type 1 diabetes who received an intensive behavioral health intervention, Novel Interventions in Children’s Healthcare (NICH).

Youths were included in the analyses if they had type 1 diabetes and at least 1 year of cost data prior to and following NICH enrollment. Outpatient, emergency department, and inpatient costs were combined. The analysis included 53 youth with the following characteristics: mean age, 14.2 years; 87% Medicaid; 58% female; 32% Black, 29% Non-Hispanic White, 28% Hispanic/Latinx, 7% Pacific Islander, 2% Asian, and 2% other racial and ethnic groups.

Average yearly costs significantly decreased from $20,400 per youth prior to NICH to $9,500 per youth afterward, largely due to inpatient charges.

“These results highlight the benefits of providing access to intensive interventions to pediatric populations experiencing health disparities,” said Dr. Wagner. “Investing early in the lives of youth experiencing health disparities is not only the right thing to do to improve patients’ health but it could also have a positive economic impact down the road.”
 

Three interventions in 300 adults with type 1 diabetes

Meanwhile, EMBARK recruited 300 patients with type 1 diabetes in the United States from clinics and community organizations who were aged 21 and older and had an elevated type 1 diabetes distress score (> 2.0) and A1c greater than or equal to 7.5%.

Participants were a mean age of 46 years, 79% were female, and 89% were White. They had a type 1 diabetes distress score of 2.8, a mean A1c of 8.3%, and 71% used an insulin pump and 79% used a continuous glucose monitor.

Participants were randomized to one of three interventions:

• Streamline: A traditional diabetes educator-led education and management program.
• Tuned-in: A psychologist-led program focused exclusively on reducing diabetes distress.
• Fixit: An integration of the two programs.

Interventions were given virtually over 3 months to small groups of 8-12 individuals and included initial workshops, one-to-one phone calls, and follow-up group meetings. Participants were then followed for 8 months.  

Researchers found statistically significant and substantial reductions in overall diabetes distress in all three interventions, with the greatest reductions in the combined intervention group, which were greater than in the educational approach alone group (P = .005).

The percentage of participants who no longer reported elevated diabetes distress at follow-up was 25% in Streamline, 37% in Tuned-in, and 42% in Fixit.

The percentage of participants who reported a minimal clinically important difference – the smallest change in a treatment outcome that an individual would identify as important – was also greatest in those in the Fixit intervention group (82%) than in the Tuned-in (74%) or Streamline (65%) interventions.
 

‘Adding the psychologist is where the real magic happens’

“The certified diabetes care specialist intervention is really a very standard thing that most clinicians would have access to; they tend to focus on knowledge and problem solving and some of the psychosocial issues,” Robert Gabbay, MD, PhD, chief scientific and medical officer for the ADA, said in an interview.

The EMBARK trial found a “graded response: CDCS alone, psychologist really focused on diabetes distress, and the two together, which would be the ideal practice model,” he noted.

There are these validated ways of measuring diabetes distress using a diabetes distress survey tool, which is also underutilized.  

“Adding the psychologist is really where the real magic happens in terms of diabetes distress,” Dr. Gabbay said.

“As you can imagine, [if] somebody ... feels powerless, it is going to be tough to manage their diabetes and unlikely to be terribly successful,” he observed. Often, these individuals are just not doing well. This study highlighted the importance of identifying this.

“I’m encouraged by the findings from the studies presented during this year’s Scientific Sessions as we continue to seek out innovative, evidence-based solutions that support people living with diabetes when they need it the most,” Dr. Gabbay concluded.

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

Interventions that specifically address diabetes distress can not only improve patient mental health but can also cut costs, according to two new studies in patients with type 1 diabetes presented at the annual scientific sessions of the American Diabetes Association.

Danielle Hessler Jones, PhD, presented findings from Behavioral Approaches to Reducing Diabetes Distress and Improving Glycemic Control (EMBARK) in adults with type 1 diabetes during an oral session.

The three-arm randomized trial found that patients had the greatest improvements in feelings of powerlessness after a 3-month behavioral intervention that combined type 1 diabetes education plus specific attention to diabetes distress.

And in a late-breaking poster, “Do The Right Thing: Behavioral Intervention for At-Risk T1D Youth,” David V. Wagner, PhD, showed that a behavioral intervention not only improved glycemic management but also reduced cost of care in disadvantaged youth.

“Diabetes distress is the emotional response to living with diabetes, the burden of relentless daily self-management, and the prospect of its long-term complications,” said Dr. Hessler Jones, professor and vice chair for research in the department of family and community medicine at the University of California, San Francisco.  

It is common, experienced by 20%-58% of people with type 1 and type 2 diabetes, and is different from depression, as it is associated with glycemic control and disease management. It “is also chronic and does not disappear on its own without intervention,” she stressed.

“It is the expected worries, concerns, and fears that are associated with struggling with a demanding and progressive chronic disease and its management,” she added.

The findings from EMBARK “suggest that distress reductions are greatest when interventions integrate education alongside approaches to address the emotional side of diabetes,” she said.  

The group is also analyzing changes in A1c with the three different interventions in EMBARK, with results expected this fall.

Dr. Hessler Jones said they also just received funding for DDASSIST, which will answer the question: “How do I translate this into care in my clinic?” The aim of the clinic training program is to bring the intervention to the diabetes care team.

“Could this program be delivered by somebody else, other than a psychologist?” an audience member asked. They will be looking at this, she replied.
 

‘Do the right thing’

For the late-breaking poster by Dr. Wagner and colleagues, researchers evaluated direct cost data from three health care systems provided for youth with type 1 diabetes who received an intensive behavioral health intervention, Novel Interventions in Children’s Healthcare (NICH).

Youths were included in the analyses if they had type 1 diabetes and at least 1 year of cost data prior to and following NICH enrollment. Outpatient, emergency department, and inpatient costs were combined. The analysis included 53 youth with the following characteristics: mean age, 14.2 years; 87% Medicaid; 58% female; 32% Black, 29% Non-Hispanic White, 28% Hispanic/Latinx, 7% Pacific Islander, 2% Asian, and 2% other racial and ethnic groups.

Average yearly costs significantly decreased from $20,400 per youth prior to NICH to $9,500 per youth afterward, largely due to inpatient charges.

“These results highlight the benefits of providing access to intensive interventions to pediatric populations experiencing health disparities,” said Dr. Wagner. “Investing early in the lives of youth experiencing health disparities is not only the right thing to do to improve patients’ health but it could also have a positive economic impact down the road.”
 

Three interventions in 300 adults with type 1 diabetes

Meanwhile, EMBARK recruited 300 patients with type 1 diabetes in the United States from clinics and community organizations who were aged 21 and older and had an elevated type 1 diabetes distress score (> 2.0) and A1c greater than or equal to 7.5%.

Participants were a mean age of 46 years, 79% were female, and 89% were White. They had a type 1 diabetes distress score of 2.8, a mean A1c of 8.3%, and 71% used an insulin pump and 79% used a continuous glucose monitor.

Participants were randomized to one of three interventions:

• Streamline: A traditional diabetes educator-led education and management program.
• Tuned-in: A psychologist-led program focused exclusively on reducing diabetes distress.
• Fixit: An integration of the two programs.

Interventions were given virtually over 3 months to small groups of 8-12 individuals and included initial workshops, one-to-one phone calls, and follow-up group meetings. Participants were then followed for 8 months.  

Researchers found statistically significant and substantial reductions in overall diabetes distress in all three interventions, with the greatest reductions in the combined intervention group, which were greater than in the educational approach alone group (P = .005).

The percentage of participants who no longer reported elevated diabetes distress at follow-up was 25% in Streamline, 37% in Tuned-in, and 42% in Fixit.

The percentage of participants who reported a minimal clinically important difference – the smallest change in a treatment outcome that an individual would identify as important – was also greatest in those in the Fixit intervention group (82%) than in the Tuned-in (74%) or Streamline (65%) interventions.
 

‘Adding the psychologist is where the real magic happens’

“The certified diabetes care specialist intervention is really a very standard thing that most clinicians would have access to; they tend to focus on knowledge and problem solving and some of the psychosocial issues,” Robert Gabbay, MD, PhD, chief scientific and medical officer for the ADA, said in an interview.

The EMBARK trial found a “graded response: CDCS alone, psychologist really focused on diabetes distress, and the two together, which would be the ideal practice model,” he noted.

There are these validated ways of measuring diabetes distress using a diabetes distress survey tool, which is also underutilized.  

“Adding the psychologist is really where the real magic happens in terms of diabetes distress,” Dr. Gabbay said.

“As you can imagine, [if] somebody ... feels powerless, it is going to be tough to manage their diabetes and unlikely to be terribly successful,” he observed. Often, these individuals are just not doing well. This study highlighted the importance of identifying this.

“I’m encouraged by the findings from the studies presented during this year’s Scientific Sessions as we continue to seek out innovative, evidence-based solutions that support people living with diabetes when they need it the most,” Dr. Gabbay concluded.

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

Could glucagonlike peptide–1 (GLP-1) receptor agonists such as semaglutide – approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk – also curb addictions and compulsive behaviors?

As demand for semaglutide for weight loss grew following approval of Wegovy by the U.S. Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.

Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in the New York Times and The Atlantic, among others.

There is also some preliminary research to support these observations.

This news organization invited three experts to weigh in.
 

Recent and upcoming studies

The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, said: “I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake.”

His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca), the first-generation GLP-1 agonist approved for type 2 diabetes, over 26 weeks, but treatment did not reduce the number of heavy drinking days (the primary outcome), compared with placebo.  

However, in post hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index > 30 kg/m²).

The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Those who had received exenatide, compared with placebo, had significantly less activation of brain reward centers when shown the pictures of alcohol.

“Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” Dr. Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, remarked in an email.

“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30 kg/m², they can of course use the compound right now,” he noted.

His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m² to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.

“Based on the potency of exenatide and semaglutide,” Dr. Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.

Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, Elisabet Jerlhag Holm, PhD, noted.

Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, department of pharmacology, University of Gothenburg, Sweden, noted in an email.

In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.

“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” said Prof. Holm.

“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”

Janice J. Hwang, MD, MHS, echoed these thoughts: “Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”

“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.

“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Dr. Hwang, who is an associate professor of medicine and chief, division of endocrinology and metabolism, at the University of North Carolina at Chapel Hill.

Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 participants with AUD who are also smokers.

They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.

Dr. Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.

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

Could glucagonlike peptide–1 (GLP-1) receptor agonists such as semaglutide – approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk – also curb addictions and compulsive behaviors?

As demand for semaglutide for weight loss grew following approval of Wegovy by the U.S. Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.

Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in the New York Times and The Atlantic, among others.

There is also some preliminary research to support these observations.

This news organization invited three experts to weigh in.
 

Recent and upcoming studies

The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, said: “I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake.”

His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca), the first-generation GLP-1 agonist approved for type 2 diabetes, over 26 weeks, but treatment did not reduce the number of heavy drinking days (the primary outcome), compared with placebo.  

However, in post hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index > 30 kg/m²).

The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Those who had received exenatide, compared with placebo, had significantly less activation of brain reward centers when shown the pictures of alcohol.

“Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” Dr. Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, remarked in an email.

“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30 kg/m², they can of course use the compound right now,” he noted.

His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m² to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.

“Based on the potency of exenatide and semaglutide,” Dr. Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.

Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, Elisabet Jerlhag Holm, PhD, noted.

Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, department of pharmacology, University of Gothenburg, Sweden, noted in an email.

In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.

“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” said Prof. Holm.

“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”

Janice J. Hwang, MD, MHS, echoed these thoughts: “Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”

“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.

“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Dr. Hwang, who is an associate professor of medicine and chief, division of endocrinology and metabolism, at the University of North Carolina at Chapel Hill.

Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 participants with AUD who are also smokers.

They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.

Dr. Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.

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

Could glucagonlike peptide–1 (GLP-1) receptor agonists such as semaglutide – approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk – also curb addictions and compulsive behaviors?

As demand for semaglutide for weight loss grew following approval of Wegovy by the U.S. Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.

Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in the New York Times and The Atlantic, among others.

There is also some preliminary research to support these observations.

This news organization invited three experts to weigh in.
 

Recent and upcoming studies

The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, said: “I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake.”

His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca), the first-generation GLP-1 agonist approved for type 2 diabetes, over 26 weeks, but treatment did not reduce the number of heavy drinking days (the primary outcome), compared with placebo.  

However, in post hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index > 30 kg/m²).

The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Those who had received exenatide, compared with placebo, had significantly less activation of brain reward centers when shown the pictures of alcohol.

“Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” Dr. Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, remarked in an email.

“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30 kg/m², they can of course use the compound right now,” he noted.

His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m² to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.

“Based on the potency of exenatide and semaglutide,” Dr. Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.

Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, Elisabet Jerlhag Holm, PhD, noted.

Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, department of pharmacology, University of Gothenburg, Sweden, noted in an email.

In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.

“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” said Prof. Holm.

“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”

Janice J. Hwang, MD, MHS, echoed these thoughts: “Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”

“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.

“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Dr. Hwang, who is an associate professor of medicine and chief, division of endocrinology and metabolism, at the University of North Carolina at Chapel Hill.

Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 participants with AUD who are also smokers.

They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.

Dr. Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.

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

A low-carbohydrate breakfast was better than a control (low-fat) breakfast to decrease glycemic variability throughout the day in type 2 diabetes, in new research.

These findings from a 3-month randomized study in 121 patients in Canada and Australia were published online recently in the American Journal of Clinical Nutrition.

The researchers aimed to determine whether a low-carbohydrate, high-fat breakfast (focused around eggs), compared with a standard, low-fat control breakfast (designed to have no/minimal eggs), would improve blood glucose control in individuals with type 2 diabetes.

“We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycemic swings,” lead author Barbara Oliveira, PhD, School of Health and Exercise Sciences, University of British Columbia, Kelowna, said in a press release from the university.

“Having fewer carbs for breakfast not only aligns better with how people with [type 2 diabetes] handle glucose throughout the day,” she noted, “but it also has incredible potential for people with [type 2 diabetes] who struggle with their glucose levels in the morning.”

“By making a small adjustment to the carb content of a single meal rather than the entire diet,” Dr. Oliveira added, “we have the potential to increase adherence significantly while still obtaining significant benefits.”

The researchers conclude that “this trial provides evidence that advice to consume a low-carbohydrate breakfast could be a simple, feasible, and effective approach to manage postprandial hyperglycemia and lower glycemic variability in people living with type 2 diabetes.”
 

Could breakfast tweak improve glucose control?

People with type 2 diabetes have higher levels of insulin resistance and greater glucose intolerance in the morning, the researchers write.

And consuming a low-fat, high-carbohydrate meal in line with most dietary guidelines appears to incur the highest hyperglycemia spike and leads to higher glycemic variability.

They speculated that eating a low-carb breakfast, compared with a low-fat breakfast, might be an easy way to mitigate this.

They recruited participants from online ads in three provinces in Canada and four states in Australia, and they conducted the study from a site in British Columbia and one in Wollongong, Australia.

The participants were aged 20-79 years and diagnosed with type 2 diabetes. They also had a current hemoglobin A1c < 8.5% and no allergies to eggs, and they were able to follow remote, online guidance.

After screening, the participants had a phone or video conference call with a member of the research team who explained the study.

The researchers randomly assigned 75 participants in Canada and 46 participants in Australia 1:1 to the low-carbohydrate intervention or the control intervention.

The participants had a mean age of 64 and 53% were women. They had a mean weight of 93 kg (204 lb), body mass index of 32 kg/m², and A1c of 7.0%.

Registered dietitians in Canada and Australia each designed 8-10 recipes/menus for low-carb breakfasts and an equal number of recipes/menus for control (low-fat) breakfasts that were specific for those countries.

Each recipe contains about 450 kcal, and they are available in Supplemental Appendix 1A and 1B, with the article.

Each low-carbohydrate breakfast contains about 25 g protein, 8 g carbohydrates, and 37 g fat. For example, one breakfast is a three-egg omelet with spinach.

Each control (low-fat) recipe contains about 20 g protein, 56 g carbohydrates, and 15 g fat. For example, one breakfast is a small blueberry muffin and a small plain Greek yogurt.

The participants were advised to select one of these breakfasts every day and follow it exactly (they were also required to upload a photograph of their breakfast every morning). They were not given any guidance or calorie restriction for the other meals of the day.

The participants also filled in 3-day food records and answered a questionnaire about exercise, hunger, and satiety, at the beginning, middle, and end of the intervention.

They provided self-reported height, weight, and waist circumference, and they were given requisitions for blood tests for A1c to be done at a local laboratory, at the beginning and end of the intervention.

The participants also wore a continuous glucose monitor (CGM) during the first and last 14 days of the intervention.
 

Intervention improved CGM measures

There was no significant difference in the primary outcome, change in A1c, at the end of 12 weeks, in the two groups. The mean A1c decreased by 0.3% in the intervention group vs 0.1% in the control group (P = .06).

Similarly, in secondary outcomes, weight and BMI each decreased about 1% and waist circumference decreased by about 2.5 cm in each group at 12 weeks (no significant difference). There were also no significant differences in hunger, satiety, or physical activity between the two groups.

However, the 24-hour CGM data showed that mean and maximum glucose, glycemic variability, and time above range were all significantly lower in participants in the low-carbohydrate breakfast intervention group vs. those in the control group (all P < .05).

Time in range was significantly higher among participants in the intervention group (P < .05).

In addition, the 2-hour postprandial CGM data showed that mean glucose and maximum glucose after breakfast were lower in participants in the low-carbohydrate breakfast group than in the control group.

This work was supported by investigator-initiated operating grants to senior author Jonathan P. Little, PhD, School of Health and Exercise Sciences, University of British Columbia, from the Egg Nutrition Center, United States, and Egg Farmers of Canada. The authors declare that they have no relevant financial relationships.

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

A low-carbohydrate breakfast was better than a control (low-fat) breakfast to decrease glycemic variability throughout the day in type 2 diabetes, in new research.

These findings from a 3-month randomized study in 121 patients in Canada and Australia were published online recently in the American Journal of Clinical Nutrition.

The researchers aimed to determine whether a low-carbohydrate, high-fat breakfast (focused around eggs), compared with a standard, low-fat control breakfast (designed to have no/minimal eggs), would improve blood glucose control in individuals with type 2 diabetes.

“We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycemic swings,” lead author Barbara Oliveira, PhD, School of Health and Exercise Sciences, University of British Columbia, Kelowna, said in a press release from the university.

“Having fewer carbs for breakfast not only aligns better with how people with [type 2 diabetes] handle glucose throughout the day,” she noted, “but it also has incredible potential for people with [type 2 diabetes] who struggle with their glucose levels in the morning.”

“By making a small adjustment to the carb content of a single meal rather than the entire diet,” Dr. Oliveira added, “we have the potential to increase adherence significantly while still obtaining significant benefits.”

The researchers conclude that “this trial provides evidence that advice to consume a low-carbohydrate breakfast could be a simple, feasible, and effective approach to manage postprandial hyperglycemia and lower glycemic variability in people living with type 2 diabetes.”
 

Could breakfast tweak improve glucose control?

People with type 2 diabetes have higher levels of insulin resistance and greater glucose intolerance in the morning, the researchers write.

And consuming a low-fat, high-carbohydrate meal in line with most dietary guidelines appears to incur the highest hyperglycemia spike and leads to higher glycemic variability.

They speculated that eating a low-carb breakfast, compared with a low-fat breakfast, might be an easy way to mitigate this.

They recruited participants from online ads in three provinces in Canada and four states in Australia, and they conducted the study from a site in British Columbia and one in Wollongong, Australia.

The participants were aged 20-79 years and diagnosed with type 2 diabetes. They also had a current hemoglobin A1c < 8.5% and no allergies to eggs, and they were able to follow remote, online guidance.

After screening, the participants had a phone or video conference call with a member of the research team who explained the study.

The researchers randomly assigned 75 participants in Canada and 46 participants in Australia 1:1 to the low-carbohydrate intervention or the control intervention.

The participants had a mean age of 64 and 53% were women. They had a mean weight of 93 kg (204 lb), body mass index of 32 kg/m², and A1c of 7.0%.

Registered dietitians in Canada and Australia each designed 8-10 recipes/menus for low-carb breakfasts and an equal number of recipes/menus for control (low-fat) breakfasts that were specific for those countries.

Each recipe contains about 450 kcal, and they are available in Supplemental Appendix 1A and 1B, with the article.

Each low-carbohydrate breakfast contains about 25 g protein, 8 g carbohydrates, and 37 g fat. For example, one breakfast is a three-egg omelet with spinach.

Each control (low-fat) recipe contains about 20 g protein, 56 g carbohydrates, and 15 g fat. For example, one breakfast is a small blueberry muffin and a small plain Greek yogurt.

The participants were advised to select one of these breakfasts every day and follow it exactly (they were also required to upload a photograph of their breakfast every morning). They were not given any guidance or calorie restriction for the other meals of the day.

The participants also filled in 3-day food records and answered a questionnaire about exercise, hunger, and satiety, at the beginning, middle, and end of the intervention.

They provided self-reported height, weight, and waist circumference, and they were given requisitions for blood tests for A1c to be done at a local laboratory, at the beginning and end of the intervention.

The participants also wore a continuous glucose monitor (CGM) during the first and last 14 days of the intervention.
 

Intervention improved CGM measures

There was no significant difference in the primary outcome, change in A1c, at the end of 12 weeks, in the two groups. The mean A1c decreased by 0.3% in the intervention group vs 0.1% in the control group (P = .06).

Similarly, in secondary outcomes, weight and BMI each decreased about 1% and waist circumference decreased by about 2.5 cm in each group at 12 weeks (no significant difference). There were also no significant differences in hunger, satiety, or physical activity between the two groups.

However, the 24-hour CGM data showed that mean and maximum glucose, glycemic variability, and time above range were all significantly lower in participants in the low-carbohydrate breakfast intervention group vs. those in the control group (all P < .05).

Time in range was significantly higher among participants in the intervention group (P < .05).

In addition, the 2-hour postprandial CGM data showed that mean glucose and maximum glucose after breakfast were lower in participants in the low-carbohydrate breakfast group than in the control group.

This work was supported by investigator-initiated operating grants to senior author Jonathan P. Little, PhD, School of Health and Exercise Sciences, University of British Columbia, from the Egg Nutrition Center, United States, and Egg Farmers of Canada. The authors declare that they have no relevant financial relationships.

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

A low-carbohydrate breakfast was better than a control (low-fat) breakfast to decrease glycemic variability throughout the day in type 2 diabetes, in new research.

These findings from a 3-month randomized study in 121 patients in Canada and Australia were published online recently in the American Journal of Clinical Nutrition.

The researchers aimed to determine whether a low-carbohydrate, high-fat breakfast (focused around eggs), compared with a standard, low-fat control breakfast (designed to have no/minimal eggs), would improve blood glucose control in individuals with type 2 diabetes.

“We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycemic swings,” lead author Barbara Oliveira, PhD, School of Health and Exercise Sciences, University of British Columbia, Kelowna, said in a press release from the university.

“Having fewer carbs for breakfast not only aligns better with how people with [type 2 diabetes] handle glucose throughout the day,” she noted, “but it also has incredible potential for people with [type 2 diabetes] who struggle with their glucose levels in the morning.”

“By making a small adjustment to the carb content of a single meal rather than the entire diet,” Dr. Oliveira added, “we have the potential to increase adherence significantly while still obtaining significant benefits.”

The researchers conclude that “this trial provides evidence that advice to consume a low-carbohydrate breakfast could be a simple, feasible, and effective approach to manage postprandial hyperglycemia and lower glycemic variability in people living with type 2 diabetes.”
 

Could breakfast tweak improve glucose control?

People with type 2 diabetes have higher levels of insulin resistance and greater glucose intolerance in the morning, the researchers write.

And consuming a low-fat, high-carbohydrate meal in line with most dietary guidelines appears to incur the highest hyperglycemia spike and leads to higher glycemic variability.

They speculated that eating a low-carb breakfast, compared with a low-fat breakfast, might be an easy way to mitigate this.

They recruited participants from online ads in three provinces in Canada and four states in Australia, and they conducted the study from a site in British Columbia and one in Wollongong, Australia.

The participants were aged 20-79 years and diagnosed with type 2 diabetes. They also had a current hemoglobin A1c < 8.5% and no allergies to eggs, and they were able to follow remote, online guidance.

After screening, the participants had a phone or video conference call with a member of the research team who explained the study.

The researchers randomly assigned 75 participants in Canada and 46 participants in Australia 1:1 to the low-carbohydrate intervention or the control intervention.

The participants had a mean age of 64 and 53% were women. They had a mean weight of 93 kg (204 lb), body mass index of 32 kg/m², and A1c of 7.0%.

Registered dietitians in Canada and Australia each designed 8-10 recipes/menus for low-carb breakfasts and an equal number of recipes/menus for control (low-fat) breakfasts that were specific for those countries.

Each recipe contains about 450 kcal, and they are available in Supplemental Appendix 1A and 1B, with the article.

Each low-carbohydrate breakfast contains about 25 g protein, 8 g carbohydrates, and 37 g fat. For example, one breakfast is a three-egg omelet with spinach.

Each control (low-fat) recipe contains about 20 g protein, 56 g carbohydrates, and 15 g fat. For example, one breakfast is a small blueberry muffin and a small plain Greek yogurt.

The participants were advised to select one of these breakfasts every day and follow it exactly (they were also required to upload a photograph of their breakfast every morning). They were not given any guidance or calorie restriction for the other meals of the day.

The participants also filled in 3-day food records and answered a questionnaire about exercise, hunger, and satiety, at the beginning, middle, and end of the intervention.

They provided self-reported height, weight, and waist circumference, and they were given requisitions for blood tests for A1c to be done at a local laboratory, at the beginning and end of the intervention.

The participants also wore a continuous glucose monitor (CGM) during the first and last 14 days of the intervention.
 

Intervention improved CGM measures

There was no significant difference in the primary outcome, change in A1c, at the end of 12 weeks, in the two groups. The mean A1c decreased by 0.3% in the intervention group vs 0.1% in the control group (P = .06).

Similarly, in secondary outcomes, weight and BMI each decreased about 1% and waist circumference decreased by about 2.5 cm in each group at 12 weeks (no significant difference). There were also no significant differences in hunger, satiety, or physical activity between the two groups.

However, the 24-hour CGM data showed that mean and maximum glucose, glycemic variability, and time above range were all significantly lower in participants in the low-carbohydrate breakfast intervention group vs. those in the control group (all P < .05).

Time in range was significantly higher among participants in the intervention group (P < .05).

In addition, the 2-hour postprandial CGM data showed that mean glucose and maximum glucose after breakfast were lower in participants in the low-carbohydrate breakfast group than in the control group.

This work was supported by investigator-initiated operating grants to senior author Jonathan P. Little, PhD, School of Health and Exercise Sciences, University of British Columbia, from the Egg Nutrition Center, United States, and Egg Farmers of Canada. The authors declare that they have no relevant financial relationships.

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