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In this episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, co-hosts Diana Isaacs, PharmD, BCPS, BC-ADM, CDCES, FADCES, and Natalie Bellini, DNP, FNP-BC, provide a comprehensive review of the 2025 American Association of Clinical Endocrinology (AACE) Annual Meeting held in Orlando, Florida. The episode captures notable sessions, emerging clinical insights, and advances in diabetes care and endocrinology presented during the conference.

The discussion opens with reflections on keynote lectures, including a plenary led by Daniel Drucker, MD, on incretin physiology and the clinical evolution of GLP-1 receptor agonists. Isaacs highlights the importance of his translational research and addresses the implications of safety concerns such as pancreatitis and thyroid cancer. Both hosts express admiration for Drucker’s role in shaping the field of incretin-based therapies.

Another highlight includes the plenary delivered by Anne L. Peters, MD, which emphasized health equity and expanding access to diabetes technology in underserved populations. Isaacs discusses Peters’ innovative use of pharmacists in insulin pump clinics and her longstanding contributions to ADA standards of care. Bellini commends Peters' dual impact in both affluent and marginalized communities.

The hosts also describe their participation in a hands-on diabetes technology workshop, where attendees rotated through device-specific stations including insulin pumps, CGMs, inhaled insulin, and smart pens. This workshop was part of a broader effort to launch a diabetes technology certification program, with both in-person and online components scheduled for release in summer 2025.

Clinical trial updates included coverage of the CONTROL-IQ Plus RCT in type 2 diabetes, studies on weekly insulin formulations, CGM use in inpatient settings, and the Inhale-3 trial on inhaled insulin efficacy. Discussions also touched on advancements in over-the-counter CGMs, data interpretation challenges in individuals without diabetes, and the proposed shift toward using time-in-normal glucose range (TING) metrics to assess glycemic control.

The episode concludes with enthusiasm for the future of patient-centered technology and anticipation for the AACE 2026 meeting in Las Vegas.

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In this episode of Diabetes Dialogue, 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, sit down with Steven Russell, MD, PhD, Chief Medical Officer at Beta Bionics, to discuss the latest real-world outcomes from the iLet Bionic Pancreas—an autonomous insulin delivery (AID) system cleared by the US Food and Drug Administration (FDA) in 2023.

Russell outlines the iLet’s fully automated design, which sets it apart from conventional AID systems by requiring no manual settings, carb ratios, or correction factors. The system determines 100% of insulin dosing, adapting continuously to glycemic trends without relying on user engagement. This autonomy makes the iLet particularly effective for individuals with suboptimal diabetes self-management or limited access to endocrinology care.

New real-world data, covering 3,300 users from the first year of commercial rollout, reveal a mean baseline A1c of 8.5%—higher than the 7.8% in the pivotal trial and reflective of the broader U.S. type 1 diabetes (T1D) population. The iLet reduced glucose management indicator to 7.3%, yielding an average A1c reduction of 1.2%, more than double that seen in the pivotal study. Outcomes were most pronounced among those with severe hyperglycemia: users starting with A1c >14% saw average reductions of 7%, with low rates of diabetic ketoacidosis (DKA) and minimal increases in hypoglycemia (median time <70 mg/dL, 1.6%; time <54 mg/dL, <0.3%).

Crucially, the iLet’s performance remains consistent regardless of user engagement. Patients who announced meals more than four times daily experienced only a 0.4% greater GMI improvement compared to those announcing meals once every three days. This supports its use in underserved populations and those with a high diabetes burden. The algorithm also adapted effectively in the presence of prior long-acting insulin, though Russell recommended limiting such adjunct therapy to no more than 50% of estimated basal needs.

Isaacs and Bellini highlighted the clinical significance of the iLet's ability to lower A1c while simultaneously reducing hypoglycemia—a rare achievement in diabetes therapy. The episode also explored the iLet’s off-label use in type 2 diabetes (T2D). While formal trials are ongoing, preliminary data from MDI-treated T2D users suggest similarly favorable outcomes.

A forthcoming trial will test the iLet in primary care settings for both T1D and T2D. Early results from a pilot study found no difference in glycemic outcomes whether training was delivered by endocrinologists or primary care providers, reinforcing the system’s potential to expand access to AID beyond specialty care.

00:00:01 Introduction and Guest Introduction

00:01:12 Early Research and Development

00:02:30 Real World Data Overview

00:26:08 Impact of Islet on A1C and Hypoglycemia

00:26:25 Clinical Considerations and User Engagement

00:27:02 Real-World Data Analysis and Future Studies

00:32:05 Conclusion and Future Prospects

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00:00:05 Introduction and Background of Luna Diabetes

00:02:27 Overview of Luna and Its Unique Features

00:04:58 Details of Luna's Functionality and User Experience

00:14:24 Clinical Trials and Feasibility Study Results

00:20:49 Potential Applications and Future Directions

00:24:54 Conclusion and Final Thoughts

In this episode of Diabetes Dialogue, 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, sit down with John Sjölund and Jon Brilliant, co-founders of Luna Diabetes, to explore their novel approach to automated insulin delivery (AID) designed specifically for individuals with diabetes using insulin pens.

The discussion introduces Luna, a small, wearable overnight patch pump that delivers automated insulin microdoses during sleep, addressing one of the most persistent gaps in diabetes care: nighttime glucose variability.

Unlike traditional AID systems that require full-day pump use, Luna is built for simplicity and intermittent use. It integrates with any continuous glucose monitor (CGM), requires no input on insulin type, and adapts automatically without user-programmed settings. The system supplements a patient’s existing basal insulin, providing algorithm-driven microdoses of rapid-acting insulin at night. The device operates with minimal user interaction—patients fill the pod with up to 10 units of insulin, apply it before bed, and remove it in the morning.

Preliminary data from Luna’s feasibility study showed promising results: an average 10% increase in time-in-range and a 15% reduction in time spent above 250 mg/dL, without increased hypoglycemia. The ongoing pivotal trial, enrolling 120 participants with type 1 diabetes (T1D), aims to further evaluate safety, efficacy, and patient-reported outcomes, particularly sleep quality, across 13 weeks. 

Sjölund and Brilliant emphasized Luna isn't designed to match the full clinical performance of traditional AID systems, but rather to expand access by lowering barriers—providing improved overnight control and reducing cognitive and emotional diabetes burden, especially for those who prefer to avoid pumps.

Isaacs and Bellini highlighted Luna’s potential not only for people with type 1 diabetes but also for those with type 2 diabetes (T2D), particularly in conjunction with GLP-1 therapies or for patients early in their insulin journey. Luna's no-training-required model could also enable broader adoption in primary care settings, where most diabetes management occurs.

Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives!

Full results from the SURMOUNT-5 trial show tirzepatide (Zepbound) led to significantly greater weight loss than semaglutide 2.4 mg (Wegovy) in adults with obesity, according to findings published in The New England Journal of Medicine and presented at the 32nd European Congress on Obesity.

“The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management,” said principal investigator Louis J. Aronne, MD, director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, in a press release.

The phase 3b trial enrolled 751 participants across 32 US and Puerto Rican sites, with 750 receiving at least one dose of study drug. Participants were randomized to their maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg). The primary endpoint was percent change in body weight at 72 weeks.

Results showed tirzepatide produced a 20.2% average reduction in body weight versus 13.7% with semaglutide, a 6.5-point difference (P<0.001). In absolute terms, patients lost 22.8 kg with tirzepatide versus 15.0 kg with semaglutide.

Tirzepatide also outperformed semaglutide for the proportion of patients achieving 10%, 15%, 20%, 25%, and 30% weight loss thresholds, with more than 64% of tirzepatide patients achieving a 15% or greater body weight reduction.

Both drugs had safety profiles consistent with previous trials, with gastrointestinal symptoms being the most common adverse events. Serious adverse events occurred in 4.8% of tirzepatide users and 3.5% of semaglutide users. Six patients from each group discontinued due to side effects.

In this special edition episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, breakdown the trial, how they interpret the findings, and how it could impact care decisions in the future.

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In this episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, break down new key updates on cotntinous glucose monitoring (CGM) systems for diabetes, incuding the Dexcom G7, Libre App, and Medtronic Simplera Sync.

On April 10, 2025, the FDA granted clearance to the Dexcom G7 15-day continuous glucose monitoring (CGM) system for individuals aged 18 years and older with diabetes. The G7 CGM now boasts the longest-lasting CGM system with 15.5 days of wear and best-in-class accuracy with a mean absolute relative difference (MARD) of 8.0%.

Isaacs and Bellini discussed the sensor life of the G7 CGM, with Dexcom announcing only 73.9% of sensors lasted the full 15 days. When using the product per package labeling, approximately 26% of sensors may not last for the full 15 days.

With the launch of the new Libre app, Abbott is replacing the Libre 2 and 3 apps with a new all-in-one app that works with all Libre sensors. With the upcoming discontinuation of Libre 2 and 3 (non-Plus) sensors in the US by September 2025, intermittent scanning will be phased out, improving data continuity and aligning with American Diabetes Association (ADA) recommendations.

They also highlight Libre’s new integration with Glooko, allowing direct data syncing via Bluetooth from the app. This streamlines clinical workflows, supports EHR integration, and includes features like voice-activated carb logging, reducing both patient and provider burden.

On April 18, 2025, the FDA approved Medtronic’s Simplera Sync sensor for use with its MiniMed 780G insulin delivery system, expanding CGM options for users. The new all-in-one, fingerstick-free sensor offers simplified insertion and enhanced user flexibility while maintaining compatibility with the system’s Meal Detection™ technology and adaptive insulin algorithm. A limited US launch is planned for fall 2025.

Isaacs and Bellini noted this long-awaited update could improve access and uptake in the US., especially for newly diagnosed patients, thanks to easier usability and compatibility with Medtronic’s strong insulin delivery algorithm.

00:00:30 Dexcom G7 15-Day Sensor Approval

00:02:11 Challenges with Sensor Lifespan

00:06:00 Education and Replacement Process

00:09:27 Accuracy and FDA Approval Details

00:11:37 Libre's New Mobile App

00:16:55 Integration with Gluco

00:19:41 Medtronic's Simplera Sync Approval

00:23:03 Future Collaborations and Algorithms

00:28:05 Final Thoughts and Wrap-Up

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In this episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, break down new Phase 3 data from the ESSENCE trial examining semaglutide 2.4 mg (Wegovy) for metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis.

With results published in The New England Journal of Medicine, hosts are joined by first author Arun J. Sanyal, MD, director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, to discuss key takeaways from part 1 of the ESSENCE trial, semaglutide’s impact on liver outcomes and weight loss, and what the data could mean for the future of MASH treatment.

Once-weekly semaglutide 2.4 mg significantly improved liver outcomes in patients with metabolic dysfunction–associated steatohepatitis (MASH) and stage 2 or 3 fibrosis, according to findings from the ESSENCE trial.

In part 1 of the ongoing, double-blind, placebo-controlled trial, 800 patients were evaluated at 72 weeks for two primary endpoints: resolution of steatohepatitis without worsening fibrosis, and fibrosis improvement without worsening steatohepatitis. Spanning 253 sites in 37 countries, the full trial enrolled 1197 biopsy-confirmed patients between May 2021 and April 2023.

At the interim analysis, semaglutide achieved both primary endpoints. Resolution of steatohepatitis without fibrosis worsening occurred in 62.9% of patients receiving semaglutide compared with 34.3% in the placebo group (difference, 28.7%; 95% CI, 21.1–36.2; P <.001). Reduction in fibrosis without worsening steatohepatitis was observed in 36.8% of the semaglutide group versus 22.4% with placebo (difference, 14.4%; 95% CI, 7.5–21.3; P <.001).

Secondary outcomes showed combined resolution of steatohepatitis and fibrosis reduction in 32.7% of semaglutide-treated patients versus 16.1% with placebo (difference, 16.5 percentage points; P <.001). Patients on semaglutide also experienced a mean body weight reduction of 10.5% versus 2.0% in the placebo group (difference: −8.5%; P <.001).

While semaglutide was linked to a slight improvement in bodily pain scores on the SF-36, the result did not reach prespecified statistical significance. Adverse events occurred in 86.3% of the semaglutide group and 79.7% of the placebo group, primarily gastrointestinal. Rates of serious adverse events were similar at 13.4% in both groups.

Resmetirom (Rezdiffra) is the only US Food and Drug Administration (FDA)-approved treatment for noncirrhotic MASH. These findings position semaglutide as a potential future option, pending results from the full ESSENCE trial and regulatory review.

00:00:01 Introduction and Participant Backgrounds

00:01:18 Overview of MASH and Insulin Resistance

00:03:28 Phase 2 and Phase 3 Trials of Semaglutide

00:07:23 Significant Findings and Clinical Implications

00:09:44 Challenges and Future Directions

00:14:50 Mechanism of Action and Weight Loss

00:17:39 Data on Weight Loss and Liver Improvement

00:20:42 Potential for FDA Approval and Future Studies

00:25:04 Conclusion and Final Thoughts

In this episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, discuss the newly published findings from the CATALYST trial, a prospective, observational study establishing the prevalence of hypercortisolism among individuals with difficult-to-control type 2 diabetes (T2D).

CATALYST enrolled 1057 adults with T2D and suboptimal glycemic control (HbA1c, 7.5–11.5%) despite treatment with ≥2 glucose-lowering agents. All participants underwent a 1-mg overnight dexamethasone suppression test (DST), and common confounders were excluded. Hypercortisolism—defined as a post-DST cortisol level >1.8 µg/dL—was identified in 23.8% of participants, with even higher rates among those with cardiac disease (33.3%) or on ≥3 antihypertensives (36.6%). Adrenal imaging revealed abnormalities in about one-third of affected individuals.

Isaacs and Bellini emphasized how striking it is that such a high proportion of patients met criteria for hypercortisolism, a condition historically considered rare. The trial challenges that perception, revealing that clinical features like persistent hyperglycemia and hypertension—despite optimized therapy—could reflect underlying endocrine dysfunction. They noted that neither A1c nor body mass index (BMI) alone predicted elevated cortisol, although medication intensity and comorbid conditions did.

The conversation explored how the recognition of hypercortisolism could alter clinical management. Future studies will assess whether targeted treatments—such as cortisol-lowering pharmacotherapy, including mifepristone (Korlym), or adrenal surgery—can reduce medication burden, improve glycemic control, and lower cardiovascular risk. Isaacs and Bellini pointed out that many patients with hypercortisolism present without the classic phenotype, underscoring the importance of broader screening criteria.

Looking ahead, they called for greater awareness among clinicians to consider screening in patients on intensive diabetes and blood pressure regimens who still fail to reach therapeutic goals. Identifying and treating hypercortisolism could open a new pathway to improving outcomes in this population.

00:00:01 Catalyst Trial Overview and Introduction

00:01:37 Patient Criteria and Initial Findings

00:04:18 Implications and Next Steps

00:05:23 Adrenal Imaging and Cardiac Disorders

00:07:22 Clinical Implications and Future Research

00:09:13 Demographic Differences and Future Directions

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In this episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, discuss the top-line results from the ACHIEVE-1 trial evaluating orforglipron—an investigational, once-daily oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed by Eli Lilly—for adults with type 2 diabetes (T2D) inadequately controlled by diet and exercise.

Isaacs and Bellini emphasized the clinical significance of orforglipron’s Phase 3 data in the ACHIEVE-1 trial, which demonstrated substantial reductions in A1c (1.3–1.6%) from a baseline of 8.0% and notable weight loss averaging 16 pounds (7.9%) at the highest dose over 40 weeks. Impressively, more than 65% of participants achieved an A1c below 6.5%, meeting the American Diabetes Association (ADA)’s target for diabetes control.

The hosts highlighted the convenience advantage of orforglipron compared to oral semaglutide, which has strict dosing requirements. Oral orforglipron can be taken without food or water restrictions, potentially increasing adherence and reducing treatment burden. They also noted the drug’s favorable safety profile, with gastrointestinal side effects similar in type and incidence to existing GLP-1 RAs, and no hepatic safety signals observed in the trial.

Beyond glycemic control, Isaacs and Bellini discussed the broader implications for obesity treatment, pointing to the drug’s potential utility in weight management, pending regulatory submission. They explored the possibility of using injectable GLP-1 RAs for initial weight loss followed by oral maintenance with orforglipron—potentially lowering costs and improving access.

The conversation touched on the upcoming ACHIEVE trial series, which will explore orforglipron in head-to-head comparisons with other agents, its use in insulin-treated T2D, and future indications including cardiovascular risk and kidney disease.

While optimistic, the hosts stressed the need for cardiovascular outcomes data to confirm orforglipron’s safety and potential benefits in this domain. If confirmed, they suggested orforglipron could become a cornerstone oral therapy for T2D and obesity.

00:00:01 Discussion on OR for GLP-1 Receptor Agonist

00:02:13 Potential Impact and Patient Preferences

00:03:59 Safety and Market Potential

00:05:13 Cost and Transition Options

00:06:32 Future Trials and Side Effects

00:08:55 Cardiovascular Outcome Data and Conclusion

In this episode of Diabetes Dialogue, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, are joined by Rifka Schulman-Rosenbaum, MD, director of inpatient diabetes at Long Island Jewish Medical Center and co-author of Establishing Screening Programs for Pre-symptomatic Type 1 Diabetes: Practical Guidance for Diabetes Care Providers, a new paper in the Journal of Clinical Endocrinology and Metabolism.

With Bellini as a co-author of the piece, experts explored the increasing clinical and operational momentum behind screening for pre-symptomatic type 1 diabetes (T1D) and what it takes to implement effective programs in real-world settings.

The conversation centers on the rationale and logistics behind identifying individuals in stages 1 and 2 of T1D—autoimmune stages characterized by multiple islet autoantibodies before clinical onset. With the availability of teplizumab (Tzield), a disease-modifying therapy shown to delay progression to stage 3 of T1D, the importance of early detection and standardized screening protocols has become more urgent.

Schulman-Rosenbaum outlined how her work on the JDRF Breakthrough T1D initiative led to the development of actionable guidance aimed at frontline diabetes care providers. She highlights barriers to implementation—such as limited provider awareness of T1D staging and screening protocols—and details her institution’s ongoing efforts to educate primary care clinicians and endocrinologists, including distributing screening handouts and creating streamlined workflows using dot phrases and dedicated follow-up slots.

The discussion emphasizes targeted screening for high-risk groups, such as first- and second-degree relatives of individuals with T1D and patients with autoimmune diseases like Hashimoto’s or celiac. Schulman-Rosenbaum emphasized the opportunity for endocrinologists to screen these patients directly during routine care and the utility of a centralized handout to guide test ordering and family engagement.

Drawing from their paper, experts outlined practical steps for launching autoantibody screening programs: nominating a program champion, forming an implementation team, and embedding screening into existing clinical systems. Experts stressed the importance of using appropriate ICD-10 codes for insurance coverage and referenced a diagnostic coding table in their publication.

Schulman-Rosenbaum also addressed the widespread issue of misdiagnosis, particularly in adults mistakenly classified as having type 2 diabetes, and outlines best practices for using antibody and C-peptide testing to refine diagnosis. She detailed her hospital’s approach to inpatient screening, noting an increased use of autoantibody testing and follow-up coordination for patients with suspected T1D or latent autoimmune diabetes in adults (LADA).

Finally, the episode highlighted how to monitor individuals who test positive for a single antibody or exhibit mild dysglycemia, noting that many fall outside established risk categories. Experts called for more research in this area and advocate for individualized monitoring strategies based on clinical risk, family history, and emerging glucose patterns—often using continuous glucose monitoring (CGM) data.

00:00:00 Introduction

00:02:18 Inspiration Behind the Paper

00:04:12 Challenges in Implementing T1D Screening

00:07:32 Educating Providers and Overcoming Barriers

00:09:32 Addressing Misdiagnosis of Diabetes

00:12:01 Inpatient Screening Practices

00:16:13 Support and Resources for Patients with Positive Antibodies

00:20:01 Conclusion and Final Thoughts

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In this episode, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, explored two key trial updates in type 2 diabetes (T2D) care at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions.

SOUL, a double-blind, placebo-controlled, event-driven trial, was designed to assess the cardiovascular effects of oral semaglutide (Rybelsus) in patients with T2D and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). A total of 9650 patients aged ≥50 years were enrolled across 450 centers in 44 countries.

Analyses showed oral semaglutide (Rybelsus) was linked to a 14% reduction in major adverse cardiovascular events (MACE) in high-risk patients with T2D. This reduction included the incidence of cardiovascular (CV) death, myocardial infarction (MI), or stroke compared to placebo (HR, 0.86; 95% CI, 0.77 to 0.96; P = .006) over a median follow-up of 47.5 months.

A 26% reduction in non-fatal MI was the primary driver of benefit, while safety findings identified gastrointestinal adverse events as more common with oral semaglutide. Based on these results, Novo Nordisk announced plans to pursue regulatory approval for a label expansion of oral semaglutide to include MACE risk reduction in adults with T2D and established CV disease.

STRIDE, a double-blind, randomized, placebo-controlled trial initiated in 2020, assessed the effects of semaglutide 1.0 mg (Ozempic) on functional outcomes, including walking distance, in patients with T2D and peripheral artery disease (PAD). Conducted across 112 sites in 20 countries, the trial randomized 792 patients to receive semaglutide or placebo for 52 weeks.

Analyses showed semaglutide use was associated with improvements in maximal walking distance, quality of life, and ankle-brachial index (ABI). SOUL met its primary endpoint, with semaglutide favoring the ratio from baseline in maximum walking distance at 52 weeks (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; P = .0004).

At week 57, the improvement in walking distance was higher with semaglutide (ETR, 1.08; P = .038). Quality-of-life scores (VascuQoL-6) at week 52 were significantly higher in the semaglutide group (median difference, 1.00; P = .011), as were improvements in pain-free walking distance (ETR, 1.11; P = .0046).

Editor’s Note: In this episode, there was an error in the discussion about the new dosing for Rybelsus in the SOUL trial. The corrected information is that the 14 mg dose is now 9 mg with the new formulation, due to improved absorption. The full corrected statement is: “Instead of 3 mg, the new dose is 1.5 mg; instead of 7 mg, it’s 4 mg; and instead of 14 mg, it’s 9 mg.”