Diabetes Dialogue: Orforglipron, Cagrilintide, and the Libre Assist

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

In this episode of Diabetes Dialogue, cohosts 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 the University Hospitals Diabetes and Metabolic Care Center, review major therapeutic and technology updates in diabetes care, beginning with newly announced topline phase 3 data for orforglipron, the first oral nonpeptide GLP-1 receptor agonist submitted to the US Food and Drug Administration (FDA).

Isaacs and Bellini first focus on the ATTAIN-MAINTAIN trial, which evaluated weight maintenance after patients transitioned from injectable incretin therapies to oral orforglipron. Bellini highlights that participants switching from semaglutide (Wegovy) maintained nearly all prior weight loss at 52 weeks, with an average regain of only 0.9 kg, while those transitioning from tirzepatide (Zepbound) experienced a modest regain of approximately 5 kg. A post hoc analysis further demonstrated substantial protection against weight regain compared with placebo, underscoring the potential role of oral GLP-1 therapy as a long-term maintenance strategy.

Isaacs and Bellini discuss the clinical implications of these findings, emphasizing patient preference, adherence, and real-world barriers to injectable therapies, such as travel, refrigeration, and injection fatigue. They note that an effective oral maintenance option—particularly one expected to be priced lower than injectable GLP-1 therapies—could significantly expand access and durability of weight loss, while still allowing flexibility to return to injectables if needed. The hosts also caution that weight regain may vary depending on prior therapy potency, reinforcing the need for individualized, shared decision-making.

The conversation then shifts to another major therapeutic milestone: the FDA submission of the amylin–GLP-1 combination cagrilintide plus semaglutide. Drawing on data from the REDEFINE trials, the hosts highlight weight reductions of up to 20% in individuals with overweight or obesity and 14–16% in those with type 2 diabetes, positioning this first-in-class combination as a potentially transformative option. They discuss the promise of expanded mechanisms of action, the possibility of improved tolerability profiles, and the broader trend toward increasingly potent incretin-based therapies, with several novel agents anticipated for approval in 2026.

In the latter part of the episode, Isaacs and Bellini turn to diabetes technology updates, spotlighting Abbott’s new Libre Assist feature, which integrates AI-powered food recognition into the Libre app. They describe how photo-based meal analysis provides real-time education on expected glycemic impact and practical dietary suggestions, framing it as a valuable tool for decision-making between clinic visits. They compare this approach with similar food-logging and glucose-response features available through Dexcom and third-party platforms, emphasizing the growing role of AI in personalized diabetes self-management.

The episode concludes with a discussion of expanded data-sharing capabilities for OmniPod 5 users on Libre systems, enabled through new cloud-to-cloud connections. The hosts stress the importance of CGM follow functionality for children, older adults, and individuals at risk for severe hypoglycemia or seizures, noting that these advances may reduce prior barriers to Libre adoption. Overall, the episode underscores rapid progress across therapeutics and technology, reinforcing a future of more flexible, patient-centered, and data-driven diabetes care.