Welcome back to Diabetes Dialogue at ADA 2025!

Diabetes Dialogue: REDFINE 1 and REDEFINE 2, with Timothy Garvey, MD, and Melanie Davies, MD

85th Scientific Sessions of the American Diabetes Association (ADA 2025)

, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, take a deep dive into the REDEFINE 1 and REDEFINE 2 trials with trial investigators W. Timothy Garvey, MD, of University of Alabama at Birmingham, and Melanie Davies, MD, of the University of Leicester.

REDEFINE 1 was a 68-week, phase 3a trial enrolling over 3400 adults without diabetes but with obesity or overweight and at least one comorbidity. Participants received once-weekly CagriSema, semaglutide alone, cagrilintide alone, or placebo alongside lifestyle intervention.

Key outcome: CagriSema led to a mean weight loss of 20.4%, vs 3.0% with placebo.

Over 50% of participants on CagriSema reached a non-obese BMI.

Gastrointestinal side effects were common (80%), but mostly mild to moderate.

REDEFINE 2 enrolled 1206 adults with type 2 diabetes and overweight or obesity, randomized to CagriSema or placebo for 68 weeks.

Key outcome: CagriSema led to 13.7% mean weight loss, vs 3.4% with placebo.

73.5% achieved an HbA1c ≤6.5% vs 15.9% on placebo.

Significant improvements were seen across all weight loss and glycemic endpoints.

The speakers also highlight the agent’s favorable side effect profile, flexibility in real-world dosing, and benefits in body composition and physical function. Garvey emphasizes the shift toward complication-centric obesity care, underscoring the need for clinician-guided treatment beyond online prescription models.

The conversation closes with a look ahead to REDEFINE 3—a cardiovascular outcomes trial including patients with and without diabetes—and other ongoing studies in the REDEFINE and REIMAGINE trial programs.

Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

Relevant disclosures for Garvey include Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Epitomee, Pfizer Inc., and Neurovalens. Relevant disclosures for Davies include Abbie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GSK, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, and Zealand Pharma.

Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. 

Davies MJ, Bajaj HS, Broholm C. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. 

Podcasts

Explore groundbreaking findings from the REDEFINE trials on CagriSema's impact on weight loss and diabetes management at ADA 2025.

Switch to Weekly Efsitora Insulin for Type 2 Diabetes Feasible, with Athena Philis-Tsimikas, MD

Once-weekly insulin efsitora alfa was well-tolerated and efficacious in people with type 2 diabetes (T2D) switching from daily basal insulin.

These findings, from the phase 3 QWINT trial in the larger QWINT program evaluating efsitora, were presented by Athea Philis-Tsimikas, MD, corporate vice president of Scripps Whittier Diabetes Institute at Scripps Health in San Diego, California, at the 

2025 American Diabetes Association (ADA) Scientific Sessions

, held June 20-23, in Chicago, Illinois. The findings were also simultaneously published in 

 spoke with Philis-Tsimikas during the meeting to learn more the QWINT program evaluating insulin efsitora alfa in differing populations with T2D and about the latest findings from the QWINT-3 trial that demonstrated weekly injections of efsitora as being non-inferior to daily insulin degludec.

Philis-Tsimikas emphasized that switching from daily to weekly insulin can less the treatment burden in people with T2D. She acknowledged that, in the future clinical setting, primary care physicians may have to adapt to a new paradigm, but it is one that will benefit their patients.

“This will be an interesting way for primary care physicians, in particular, to use insulin, because this is a larger dose than you're normally used to giving… allowing physicians to understand how to give that first dose to get [patients] up to steady state, and then give a maintenance dose thereafter, might be a learning curve, but knowing that the patients overall really like this and it leads to good outcomes for their glucose control, make it worthwhile in the long run,” Philis-Tsimikas told 

Philis-Tsimikas's disclosures include Dexcom, Lilly, Medtronic, and Novo Nordisk.

Philis-Tsimikas A, Bergenstal RM, Bailey TS, et al. Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial. Published online June 22, 2025. DOI: 10.1016/S0140-6736(25)01044-X

Videos

Philis-Tsimikas shared the latest findings demonstrating inferiority after switching from daily basal insulin to weekly insulin efsitora.

Once-Weekly Insulin Efsitora a Practical Option for Type 2 Diabetes, with Athena Philis-Tsimikas, MD

Diabetes Dialogue: Updates from Dexcom at ADA 2025, with Kevin Sayer

, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, welcome Kevin Sayer, chief executive officer of Dexcom, for a candid conversation about the evolving landscape of continuous glucose monitoring (CGM). From Dexcom’s origins to the latest updates on G7 and the emerging Stelo app, the discussion traces the company's journey and innovation roadmap.

Sayer reflects on how sharing real-time glucose data transformed the diabetes management experience—making life safer not just for children but also for adults living independently, caregivers, and entire family networks. Dexcom’s emphasis on data transparency has laid the groundwork for a broader shift toward individualized care, especially for those with type 2 diabetes.

The episode dives into Dexcom’s growing footprint in type 2 diabetes management, with expanded coverage across the nation’s three largest pharmacy benefit managers. Sayer emphasizes that CGM is not just about preventing hypoglycemia in insulin users anymore—it’s a behavioral and educational tool. Patients can now “see” the impact of food choices, physical activity, and medication adherence in real time, prompting lifestyle changes that might otherwise take years of trial-and-error clinical encounters.

The hosts also explore the integration of AI-powered features like food recognition, enhancements in the Stelo app for wellness tracking, and the implications of new CGM algorithms as G7 expands to 15-day wear. Sayer addresses the unique needs of people with and without diabetes and the regulatory constraints in tailoring CGM algorithms to specific use cases.

In a lighter moment, Sayer shares his enthusiasm for Dexcom’s public-facing campaigns, including recent collaborations with Lance Bass and Nick Jonas as well as the company’s network of “Dexcom Warriors.”

Kevin Sayer joins the program to discuss the latest from Dexcom and preview where the business is headed in an evolving diabetes landscape.

Julio Rosenstock, MD
Credit: American Diabetes Association

 starting insulin therapy, a once-weekly insulin named efsitora alfa is just as effective in lowering blood glucose as a daily regimen with basal insulin, according to a new study.

Named the QWINT-1 trial, the study, which was presented at the 

, once-weekly efsitora alfa was associated with a reduction in HbA1c from 8.20% at baseline to 7.05% at week 52 compared to a reduction from 8.28% to 7.08% among the placebo group.

“The results confirm once-weekly insulin efsitora can deliver similar level of blood sugar control as daily basal insulin, with the added benefit of a simpler dosing schedule,” said lead investigator Julio Rosenstock, MD, senior scientific advisor of Velocity Clinical Research at Medical City Dallas, and clinical professor of medicine at the University of Texas Southwestern Medical Center.

Part of the QWINT clinical trial program, QWINT-1 was launched in 2023 to explore the safety and efficacy of a fixed-dose regimen of once-weekly efsitora alfa relative to daily basal insulin among patients with type 2 diabetes who are insulin-naive. The other trials in the program are also aimed at assessing once-weekly efsitora alfa for adults with diabetes. QWINT-2 evaluated insulin-naïve adults with type 2 diabetes, QWINT-3 studied those switching from daily basal insulin, QWINT-4 assessed patients intensifying from basal-bolus regimens, and QWINT-5 focused on adults with type 1 diabetes transitioning from daily basal insulin.

A 52-week, phase 3, open-label, treat-to-target trial, QWINT-1 randomized 795 patients in a 1:1 ratio to receive once-weekly efsitora or once-daily insulin glargine U100. Per trial protocol, efsitora alfa was initiated as a single dose of 100 units administered once weekly, with dose adjustments made every 4 weeks, as needed, at fixed doses of 150, 250, and 400 unites to achieve fasting blood glucose levels of 80 to 130 mg/dL while doses of glargine were adjusted weekly or more often according to a standard algorithm to reach the same glycemic goals.

For inclusion in the trial, patients needed to be adults with type 2 diabetes who had not previously received insulin, have an HbA1c of 7.0% to 10.0%, and have a BMI of 45.0 kg/m2 or less. Patients could still participate in the trial if they had received stable treatment with 1 to 3 noninsulin glucose-lowering agents for at least 3 months before screening. The overall study cohort had a mean age of 56.3 (SD, 9.8) years, 49.9% were female, 68.3% were White, 93.5% were using metformin, and had a mean duration of diabetes of 9.4 (SD, 6.7) years.

The trial's primary outcome of interest was the change from baseline in HbA1c at 52 weeks, which was assessed for noninferiority with a noninferiority margin of 0.4 percentage points.

Results of the study suggested the mean HbA1c level decreased from 8.20% at baseline to 7.05% at week 52 with efsitora alfa (least-squares mean change, -1.19 percentage points) and from 8.28% to 7.08% with daily basal insulin (least-squares mean change, -1.16 percentage points), which correlates to an estimated between-group difference of −0.03 percentage points (95% confidence interval [CI], -0.18 to 0.12). Investigators noted noninferiority was confirmed but superiority of the once-weekly approach was not shown (

 = .68). Additionally, 52-week results demonstrating the mean total weekly insulin use was 289.1 units per week with efsitora alfa and 332.8 units per week with daily basal insulin (estimated between-group difference, -43.7 units per week; 95% CI, -62.4 to -25.0).

Analysis of safety data from the trial suggested the rate of clinically significant hypoglycemia or severe hypoglycemia was lower with efsitora alfa than with daily basal insulin (0.50 vs 0.88 events per participant-year; estimated rate ratio, 0.57 [95% CI, 0.39 to 0.84]). Investigators also pointed out the median number of dose adjustments needed among participants was 2 with efsitora alfa and 8 with daily basal insulin.

“The novel fixed-dose regimen used in QWINT-1 for once-weekly efsitora, with titration options of only four different doses, has the potential to facilitate and ease the burden of starting insulin for both patients and providers, hopefully, improving adherence and long-term health outcomes, is a significant step forward in filling a treatment gap that existed for decades," Rosenstock added.

In a linked editorial, Julie R. Ingelfinger, MD, a professor of Pediatrics at Harvard Medical School, and Clifford J. Rosen, MD, director of Clinical and Translational Research and a senior scientist at Maine Medical Center's Research Institute, noted the importance of expanding patient choice within diabetes management, called attention to the limitations of trials assessing weekly insulins, and highlighted the dosing regimen used in the trial could serve as a guide if efsitora alfa were to receive regulatory approval.

“The present trial of efsitora potentially offers a ready-made and possibly straightforward algorithm for dose escalation. If packaged at a widely affordable price, efsitora would most likely simplify glycemic control for many persons with type 2 diabetes. In all, weekly or, eventually, even more widely spaced insulin preparations may facilitate easier-to-administer insulin and dependable control of diabetes, thus lessening the barriers to the effective therapy of type 2 diabetes,” wrote the pair.

Rosenstock J, Bailey T, Connery L. Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy. 

American Diabetes Association. Once-Weekly Insulin Efsitora Achieves Comparable A1C Reduction to Daily Insulin Therapy. PR Newswire. Published June 22, 2025. Accessed June 22, 2025. 

https://www.prnewswire.com/news-releases/once-weekly-insulin-efsitora-achieves-comparable-a1c-reduction-to-daily-insulin-therapy-302487408.html

Ingelfinger JR, Rosenson CJ. Weekly Insulins and Therapeutic Burden in Type 2 Diabetes. 

Articles

A recent study has shown that once-weekly insulin efsitora alfa is as effective as daily basal insulin in lowering blood glucose for type 2 diabetes patients. The QWINT-1 trial demonstrated a similar reduction in HbA1c levels between the two regimens, with efsitora alfa offering a simpler dosing schedule. The trial also indicated lower rates of hypoglycemia and fewer dose adjustments with efsitora alfa. Experts suggest that this novel regimen could improve adherence and long-term outcomes, potentially simplifying diabetes management if approved and affordably priced.

A new study reveals once-weekly efsitora alfa effectively lowers blood glucose in type 2 diabetes. 

QWINT-1: Weekly Insulin Efsitora Matches Daily Insulin in Type 2 Diabetes

Validating Intermittent Fasting for T2D, with Felicia Steger, PhD, RD

Two kinds of intermittent fasting, time-restricted eating (TRE) and intermittent energy restriction (IER), led to clinical improvements in HbA1c, glucose AUC, and body weight, in new findings from a 6-month lifestyle intervention in people with type 2 diabetes (T2D).

Investigator Felicia Steger, PhD, RD, Assistant Professor, Endocrinology, Diabetes and Clinical Pharmacology, University of Kansas Medical Center, presented these findings at the 

HCPLive spoke with Steger during the meeting to learn more about the intervention, which evaluated effects of TRE+ER and IER alone and how it aims to add more evidence to the field on intermittent fasting’s potential for helping manage T2D. Notably, the intervention included people with T2D that are taking insulin, something that she noted was atypical in other similar studies.

Steger went over the trial’s safety and efficacy findings, stressing that the trial prioritized safety of its participants in regard to medication modulation and preventing hypoglycemic events. She also discussed questions that remain with intermittent fasting in T2D and high priority research that she would like to see conducted next.

“One of the things that we wanted to do was actually provide some evidence that patients with type two diabetes who are a little bit more progressed in the disease states, could still benefit from intermittent fasting,” Steger told 

. “Many studies that have patients with type two diabetes in trials with intermittent fasting are excluding those that are taking insulin. So that's one difference between other trials and our study, we actually included those folks who are taking insulin to see, can we do this safely and effectively?”

Steger has no relevant disclosures to report.

Steger F, Grdinovac K, Donnelly J, et al. Effects of a 6-Month Lifestyle Intervention for Type 2 Diabetes Featuring Intermittent Energy Restriction or Time-Restricted Eating on Glucose Tolerance and Body Weight. Presented at: ADA 2025; June 20-23; Chicago, Illinois. Poster #1910 LB

Steger discussed findings from a 6-month lifestyle investigating TRE+ER and IER.

Elizabeth Staton-Mitchell, BA
Credit: Emory University

A global study suggests expanding access to semaglutide could save 28 million lives globally over the next 5 years.

Results of the study, which were presented at the 

, suggest universal access could significantly reduce the burden of type 2 diabetes, obesity, and related health outcomes worldwide.

Led by investigators from Emory University, the study aimed to estimate the potential public health impact of providing universal access to semaglutide across 196 countries. Using a validated microsimulation model, researchers integrated age-, sex-, and country-specific prevalence and incidence data from the 2021 Global Burden of Disease and NCD-RisC studies. The model assessed the 5-year impact of universal semaglutide access on type 2 diabetes, obesity, cardiovascular disease, chronic kidney disease, stroke, end-stage kidney disease, and all-cause mortality.

Of the estimated 6.1 billion adults globally, 19.0%—or over 1.1 billion individuals—met eligibility criteria for semaglutide treatment based on a global prevalence of 8.76% for type 2 diabetes and 16.4% for obesity.

The simulation projected that universal access to semaglutide could reduce 5-year all-cause mortality by 7.41%, translating to approximately 28 million fewer deaths (absolute change: –0.29%; 95% CI, –0.47 to –0.10%). It could also lower global obesity prevalence by 21.9%, or about 330 million fewer people with obesity (absolute change: –5.42%; 95% CI, –6.48 to –4.36%).

For more on this study and the results, check out our Q&A interview with presenting author Elizabeth Staton-Mitchell, BA, a PhD student at Emory University, from the floor at ADA 2025.

Exploring the Impact of Universal GLP-1 RA Access

This study doesn’t necessarily impact clinical care today, but it raises a powerful “what if” scenario. Before we dive into the specifics, were you surprised by the effect size and outcomes in this microsimulation?

 Definitely, and we went through a lot of rounds of validation—like, is this correct?—because the results had a shock value. When we initially prepared the abstract, our estimates were a bit lower. And when we framed the findings as a percentage point change in mortality or obesity prevalence, it seemed modest—say 9% of cases avoided—but that actually represents a 50% reduction in total prevalence. That’s a huge impact. One key point that often gets missed is the downward shift in obesity class—class 3 to class 2, class 2 to class 1. The headline about a 50% reduction only reflects class 1 to no obesity, but the broader improvement across severity levels is also really important.

 A major debate around GLP-1s has been about access and affordability—particularly for those who need them most. Did your team investigate the potential cost or cost-effectiveness of universal access?

Yeah, that’s definitely a future area of research for our team and Dr. Shao’s group. We often study subgroup-specific cost-effectiveness and try to identify the highest-benefit users. Given the limits on supply, access, and cost, our goal would be to find the people for whom these therapies would offer the greatest public health return.

Looking at the results overall, which statistics or takeaways do you think best highlight the value of getting these therapies into the hands of patients?

 It’s tough to balance the population-level versus individual-level perspective. A 50% reduction in obesity is striking, but what that means for a single patient is less direct. We used clinical trial-based BMI reductions, and the typical drop over a year was about five BMI points. As a statistician, you can translate that into probabilities, but it doesn’t always click at the patient level. Still, if you're treating a broad population, you should expect substantial benefits in both obesity and mortality.

You estimate millions of lives saved over 5 years. Was this mortality benefit mostly tied to reduced obesity itself, or more so to the downstream effects on other diseases like cardiovascular or kidney disease?

That’s a great question. We used peer-reviewed disease risk equations, and for nearly every condition we modeled—CKD, cardiovascular disease, end-stage renal failure—obesity was a major risk multiplier. So, the reduction in obesity-related morbidity really drove the mortality benefit. In the Americas, for example, the impact came largely from chronic diseases like cardiovascular disease. In other regions, competing health risks diluted the mortality benefit somewhat.

 How do you view the relevance of these findings from a broader public health standpoint?

We really hope this serves as a conversation starter. No one’s asked this "what if" question at scale before using simulation. We’ve been framing it as: imagine 25 years from now—we’ve solved the supply chain, there are generics, and everyone who needs these drugs has access. Ideally, this can help guide policy, influence pricing discussions with pharma, and promote a global conversation that extends beyond the U.S. and European markets.

Staton-Mitchell has no relevant disclosures to report.

Staton E, Li P, Lee J, et al. Universal Access to GLP1-RAs Could Reduce Global Obesity Prevalence by 20% and Save 28 Million Lives over Five Years–A Microsimulation Study. Presented at: 85th American Diabetes Association Scientific Sessions. June 20 – 23, 2025. Chicago, Illinois.

A global study led by Emory University researchers suggests that universal access to semaglutide could significantly reduce type 2 diabetes, obesity, and related health outcomes, potentially saving 28 million lives over five years. The study utilized a validated microsimulation model to assess the impact of semaglutide access across 196 countries, revealing a potential 7.41% reduction in all-cause mortality and a 21.9% decrease in global obesity prevalence. The findings highlight the importance of addressing access and affordability issues to maximize public health benefits.

A global study reveals that universal access to semaglutide could save 28 million lives and significantly reduce obesity and diabetes worldwide.

Universal Semaglutide Access Could Save 28 Million Lives in 5 Years, Study Finds

W. Timothy Garvey, MD
Credit: University of Alabama at Birmingham

Data from REDEFINE 1 and REDEFINE 2 indicate coadministration of cagrilintide 2.4 mg and semaglutide 2.4 mg (CagriSema) was associated with weight reductions in the highest range of existing weight loss interventions.

 results of the Novo Nordisk-sponsored trials offer the greatest insight yet into the effects of CagriSema, which is a combination of cagrilintide, a dual amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist.

“In REDEFINE 1, participants saw significant and clinically meaningful weight loss under a protocol that allowed investigators to maintain patients on a submaximal dose if deemed best for the patient. We also witnessed low, single-digit discontinuation rates due to adverse events in both REDEFINE 1 and 2,” said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk.

 “These results reinforce our confidence in CagriSema, and we continue to study the potential of this combination through the REDEFINE trials.”

A phase 3a, 68-week, double-blind trial, REDEFINE 1 randomized 3417 adults in a 21:3:3:7 ratio to receive once-weekly CagriSema (n=2108), semaglutide 2.4 mg alone (n=302), cagrilintide 2.4 mg alone (n=302), or placebo (n=705), all alongside standardized lifestyle interventions.

For inclusion, patients need to be adults with a BMI of 30 kg/m2 or greater, or 27 or greater with at least one obesity-related comorbidity, such as hypertension, dyslipidemia, or obstructive sleep apnea. Patients were excluded if they had type 1 or type 2 diabetes.

The primary outcomes of interest were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with CagriSema as compared with placebo.

Results of the trial suggested patients receiving CagriSema achieved a mean body weight reduction of 20.4%, compared to 3.0% with placebo at week 68, which correlates to an estimated treatment difference of –17.3 percentage points (95% CI, –18.1 to –16.6; 

<.001). Additionally, the CagriSema group had a significantly greater proportion of participants achieving weight loss of at least 5%, 20%, 25%, and 30% compared with placebo (

<.001 for all thresholds). Of note, 50.7% of patients receiving CagriSema reached the BMI threshold for non-obesity by the end of the trial relative to 10.2% of the placebo group.

Safety data suggested gastrointestinal adverse events were the most common side effects, which occurred among 79.6% of participants on CagriSema and 39.9% on placebo. Investigators pointed out events, which included nausea, vomiting, and diarrhea, were mostly mild to moderate in severity and transient.

A phase 3a, double-blind, randomized trial, REDEFINE-2 randomized 1206 participants from 12 countries in a 3:1 ratio to receive once-weekly cagrilintide-semaglutide or placebo, along with lifestyle intervention, for 68 weeks. For inclusion in the trial, patients needed to be adults with a BMI of 27 kg/m2 or more, an HbA1c of 7% to 10%, and type 2 diabetes.

The study population had a mean age of 56.0 years, 52.8% were men, 66.4% were White, and 28.7% were Asian. When examining clinic factors at baseline, the study population had a mean body weight of 102.2 kg, mean BMI of 36.2 kg/m2, mean waist circumference of 115.8 cm, and a mean HbA1c of 8.0%.

The primary endpoints of interest for REDEFINE 2 were the percent change in body weight and the percentage of patients with a reduction in body weight of 5% or more from baseline to week 68.

At week 68, patients in the CagriSema group experienced a mean weight reduction of 13.7%, compared to 3.4% with placebo, which correlates to an estimated treatment difference of −10.4 percentage points (95% CI, −11.2 to −9.5; 

<.001), with significantly more participants on CagriSema achieved weight loss of at least 5%, 10%, 15%, and 20% (

<.001 for all comparisons). Investigators also highlighted improvements in glycemic control, 73.5% of patients in the CagriSema group achieving an HbA1c of ≤6.5% compared to 15.9% in the placebo group.

"In REDEFINE 1, CagriSema provided weight loss in the highest range of efficacy observed with existing weight loss interventions,” said lead investigator Timothy Garvey, MD, professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham. “Investigators were allowed some flexibility in dose adjustments to balance efficacy and safety, but regardless of dose adjustments participants lost significant weight. These findings are relatable to clinical practice, where dosing is often adjusted based on individual needs and clinical judgement.”

Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. 

Davies MJ, Bajaj HS, Broholm C. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. 

Novo Nordisk. Novo Nordisk A/S: CagriSema 2.4 mg / 2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in New England Journal of Medicine. Novo Nordisk. Published June 22, 2025. Accessed June 22, 2025. 

https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916353

Coadministration of cagrilintide and semaglutide (CagriSema) demonstrated significant weight reduction in the REDEFINE 1 and 2 trials, surpassing existing weight loss interventions. REDEFINE 1, a 68-week trial, showed a 20.4% mean weight reduction with CagriSema compared to 3.0% with placebo. REDEFINE 2, involving type 2 diabetes patients, reported a 13.7% weight reduction with CagriSema versus 3.4% with placebo, alongside improved glycemic control. Gastrointestinal adverse events were common but mostly mild. These findings suggest CagriSema's potential in clinical practice for weight management.

CagriSema shows weight loss results in recent trials comparable to existing interventions. 

ADA 2025: CagriSema Demonstrates Dual Benefit in Obesity and Type 2 Diabetes

Personalized Diabetes Prevention: Insights from 15 Years of the VA MOVE! Program, with Qiaochu Xue, PhD, MPH

A 15-year analysis of the VA MOVE! Program, a Diabetes Prevention Program (DPP)-style lifestyle intervention, found a 24% relative risk reduction in 

 overall, although there was substantial variation in individual responses.

Further research of the data from the program, led by Qiaochu Xue, PhD, MPH, Post-Doctoral Fellow at the Emory Global Diabetes Research Center, has identified 10 key effect modifiers and developed a personalized prediction algorithm to identify individuals who stand to receive the greatest benefits from participating in the program.

“We know that most of the participants may not benefit equally… these differences may be partly from the different baseline characteristic, clinical biomarkers, and indicators, and we would like to explore the heterogeneity in their treatment response to the MOVE! Program,” Xue told 

 background on the VA MOVE! program and its main findings before going more into detail on what her research focused on. She went over some of the key effect modifiers, which were clinical, physical and mental. She also emphasized the personalized prediction algorithm’s potential to engage or reengage participants to the VA MOVE! study as average uptake remains low. Lastly, she discussed some future research that she would like to see conducted with other DPP interventions like VA MOVE! and other questions she would like to see answered.

“There are 2 opportunities here, to identify and prioritize those high benefits groups, and then, enhance the program engagement for the non-responders,” Xue said.

Xue Q, Li P, Lee J, et al. ADA Presidents' Select Abstract: Heterogeneous Treatment Effects of the VA MOVE! Weight Management Program in Preventing Type 2 Diabetes. Presented at ADA 2025; June 20-23; Chicago, Illinois. Presentation #159-OR

Xue discussed her research developing a personalized prediction algorithm for predicting responders to a DPP-style intervention.

A phase 3 trial from China indicates use of ecnoglutide, a biased GLP-1 receptor agonist, could provide significant reductions in body weight among patients with 

Named the SLIMMER trial, results of the study, which were presented at the 

, offer evidence of the agent’s safety and effects on body weight at 40 weeks among more than 600 participants.

Formerly known as XW003, ecnoglutide is a novel cAMP-biased GLP-1 analogue that selectively induces cAMP production over β-arrestin recruitment, which developers suggest could improve efficacy.

The SLIMMER study enrolled 664 participants who were randomized 3:3:3:1:1:1 to ecnoglutide at doses of 1.2 mg, 1.8 mg, or 2.4 mg, or corresponding volume-matched placebo, for 40 weeks. For inclusion in the trial, patients were required to have a BMI between 24 and 28 kg/m2 with at least 1 weight-related comorbidity.The cohort had a mean age of 34.2 years (SD, 7.6), a mean bodyweight of 91.3 kg (SD, 16.1), a mean BMI of 32.5 (4.1) kg/m2, and a mean waist circumference of 104 (SD, 10.7) cm.

The coprimary endpoints were the percentage change in bodyweight and the proportion of participants achieving at least 5% weight loss at week 40.

Primary results showed dose-dependent weight loss across all ecnoglutide arms compared to placebo (

Results demonstrated the proportion of patients achieving weight loss of 5% or more at week 40 was 77% in the ecnoglutide 1.2 mg group, 84% in the ecnoglutide 1.8 mg group, and 87% in the ecnoglutide 2.4 mg group. In contrast, this was achieved by 16% of the placebo group (

<.0001 for all). Investigators noted the respective estimated treatment differences relative to placebo were 60% (98% CI, 50 to 71), 68% (98% CI, 58 to 78), and 70% (98% CI, 61 to 80).

Analysis of safety data indicated adverse events were reported in 93% of ecnoglutide-treated participants and 84% of those on placebo, with mild-to-moderate gastrointestinal issues being most common. Investigators noted a total of 10 participants discontinued due to adverse events. Investigators also pointed out data from the study suggested patients receiving higher doses of ecnoglutide continued to see weight loss up to week 48, which could indicate a greater benefit achieved with continued care.

In a linked editorial, Tricia Tan, MBChB, PhD, of Imperial College London, commended study investigators of their efforts and applauded the community’s enthusiasm for development of GLP-1 receptor agonists but questioned the viability of these agents in the growing landscape of established therapies.

“The development of biased GLP-1 receptor agonists has been met with enthusiasm from the pharmaceutical industry, but does this design feature really confer any added clinical advantage? Unfortunately, these results, taken together with those from orfloglipron, do not provide any direct evidence to support this hypothesis,” Tan wrote.

 “To address this question, a study comparing the clinical effects of a biased GLP-1 analogue with those of a pharmacokinetically matched but balanced GLP-1 analogue would be needed: only then will the clinical role of this design feature be clear.”

Ji L, Gao L, Xue H, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. 

Tan TM-M. Is biased agonism helpful in the treatment of obesity with the GLP-1 receptor analogues? 

A phase 3 trial in China evaluated ecnoglutide, a biased GLP-1 receptor agonist, for weight reduction in overweight or obese patients. The SLIMMER trial, involving over 600 participants, demonstrated significant dose-dependent weight loss with ecnoglutide compared to placebo over 40 weeks. The study showed a high percentage of participants achieving at least 5% weight loss, with mild-to-moderate gastrointestinal adverse events reported. Despite promising results, questions remain about the clinical advantage of biased GLP-1 receptor agonists compared to established therapies, as highlighted in a linked editorial.

A phase 3 trial reveals ecnoglutide significantly reduces body weight in overweight patients, showcasing its potential as a novel obesity treatment.

SLIMMER: Ecnoglutide Demonstrates Weight Loss Potential in Phase 3 Trial

Subodh Verma, MD
Credit: Unity Health Toronto

New data from the STRIDE trial suggest the benefits of semaglutide 1.0 mg (Ozempic) on 

 could be even more substantial than the initial trial indicated.

A subanalysis of the trial presented at the 

, results shed further light on the benefit seen in the trial, which new data suggests was presented regardless of HbA1c level, SGLT2 inhibitor use, duration of diabetes, and other factors.

“These findings indicate that clinicians can now recognize semaglutide as a vascular protective medication, with benefits that extend beyond lowering weight or A1C,” said Professor Subodh Verma, MD, PhD, FRCSC, FAHA, FCAHS, cardiovascular surgeon, University of Toronto, Toronto, Canada, and senior author of the STRIDE trial.

American College of Cardiology 2025 Annual Scientific Sessions

 and funded by Novo Nordisk, STRIDE was a double-blind, randomized, placebo-controlled study initiated in 2020 to evaluate the effects of semaglutide 1.0 mg on walking distance in patients with type 2 diabetes PAD. Conducted in 20 countries, the trial enrolled and randomized 792 patients in a 1:1 ratio to receive semaglutide or placebo for 52 weeks.

The study population had a median age of 68.0 (IQR, 61.0 to 73.0), median BMI of 28.7 kg/m² (IQR, 25.6 to 33.0), 75% were male, and 68% were White. Baseline assessment of disease information indicated 61% had a duration of diabetes of 10 years or longer, and 59% had a BMI of less than 30 kg/m².

The primary endpoint, the ratio from baseline in maximum walking distance at 52 weeks, favored semaglutide (1.21 [interquartile range, 0.95–1.55] vs 1.08 [0.86–1.36]), with an estimated treatment ratio (ETR) of 1.13 (95% CI, 1.06–1.21; 

 = .0004). Secondary outcomes further supported semaglutide’s benefit. At week 52, the improvement in walking distance was greater (ETR, 1.08; 

 = .038), quality-of-life scores (VascuQoL-6) were significantly higher (median difference, 1.00; 

 = .011), and pain-free walking distance (ETR, 1.11; 

 = .0046) also improved more with semaglutide than with placebo therapy.

At ADA 2025, Verma presented a subanalysis of the trial demonstrating use of semaglutide was associated with significantly improved walking outcomes in people with PAD and diabetes, enhanced quality of life, and reduced the risk of disease progression by 54%. Verma also highlighted an estimated median ratio to baseline in maximum walking distance was 1.21 in the semaglutide group compared to 1.08 in the placebo group at week 52.

Additionally, efficacy data indicated the effects of semaglutide observed in the study were independent of baseline glycemic control, duration of diabetes, or intensity of diabetes, with further data suggesting the effects were consistent across BMI categories and irrespective of background SGLT2 inhibitor use.

Verma also presented additional safety data from the trial. These data demonstrated semaglutide was well tolerated, with no treatment-related deaths and a safety profile consistent with prior data from the agent.

“The totality of data now suggest that in people with diabetes, semaglutide favorably affects the pipes [atherosclerosis], pump [heart failure], filter [kidney outcomes]. And, in patients with PAD, these new data provide robust evidence that semaglutide is a therapy to improve their function, quality of life, and progression of disease,” Verma added.

Verma S. Diabetes and Peripheral Artery Disease—Evolving Role of GLP-1 RA and New Insights from the STRIDE Trial. Presented at: 85th American Diabetes Association Scientific Sessions. June 20 – 23, 2025. Chicago, Illinois.

American Diabetes Association. Semaglutide Increases Walking Capacity in Patients with Peripheral Artery Disease and Type 2 Diabetes | American Diabetes Association. Diabetes.org. Published June 21, 2025. Accessed June 21, 2025. 

https://diabetes.org/newsroom/press-releases/semaglutide-increases-walking-capacity-patients-peripheral-artery-disease

Campbell P. STRIDE: Semaglutide Improves Functional Outcomes in Peripheral Artery Disease. HCP Live. Published March 29, 2025. Accessed June 21, 2025. 

https://www.hcplive.com/view/semaglutide-improves-functional-outcomes-in-peripheral-artery-disease

New findings from the STRIDE trial reveal that semaglutide 1.0 mg significantly benefits individuals with type 2 diabetes and peripheral artery disease (PAD), enhancing walking distance, quality of life, and reducing disease progression risk by 54%. These effects are consistent regardless of HbA1c levels, diabetes duration, or SGLT2 inhibitor use. The trial, involving 792 patients, demonstrated semaglutide's superiority over placebo in improving maximum walking distance and quality-of-life scores. Semaglutide was well tolerated, with a safety profile aligning with previous data, offering a promising vascular protective therapy.

New findings reveal semaglutide significantly enhances walking ability and quality of life for patients with T2D and PAD.

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