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This episode covers the recent approval of oral semaglutide for T2D and a pre-specified subanalysis of the SELECT trial.
Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives!
In this episode, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, meet in person at the Diabetes Technology Meeting (DTM) in San Francisco to discuss the latest clinical and regulatory advances surrounding semaglutide.
00:00:01 Introduction
00:00:42 Oral semaglutide's FDA approval
00:02:02 The SOUL trial and Rybelsus's cardiovascular indication
00:03:35 Dosing for Rybelsus
00:06:18 The SELECT trial
00:08:29 Can GLP-1s be cardiovascular treatments?
00:14:08 Outro
The conversation opens with the recent US Food and Drug Administration (FDA) approval of oral semaglutide (Rybelsus) for reducing cardiovascular risk in adults with type 2 diabetes and established cardiovascular disease. This marks a major milestone as the first and only oral GLP-1 receptor agonist to receive a cardiovascular risk–reduction indication. Isaacs and Bellini emphasize how this approval validates the cardiovascular benefits previously observed with injectable semaglutide, offering clinicians a new oral option for patients who are resistant to injections while maintaining evidence-based protection against major cardiovascular events.
They highlight that this new indication builds upon data from the SOUL trial, which confirmed the cardiovascular benefit of oral semaglutide, and discuss how this approval will expand adoption among patients seeking non-injectable therapies. The hosts underscore practical considerations for its use - namely, that oral semaglutide must be taken on an empty stomach with up to four ounces of water and separated from food and other medications by at least 30 minutes to ensure reliable absorption. They also preview upcoming developments, including next-generation formulations expected to offer higher potency (25 mg and 50 mg) and enhanced convenience for patients, potentially broadening access and adherence.
Transitioning to recent research, Isaacs and Bellini analyze a pre-specified subanalysis from the SELECT trial, published in The Lancet, which explored whether semaglutide’s cardiovascular benefits are mediated by weight loss or by intrinsic molecular mechanisms. Interestingly, the data revealed little correlation between weight loss and reductions in cardiovascular events, suggesting that semaglutide may exert direct anti-inflammatory or disease-modifying effects independent of its impact on body weight or glycemia. Drawing parallels to statins, the hosts note that GLP-1 receptor agonists may provide cardiovascular protection beyond their metabolic effects.
They further discuss implications for the broader incretin class - GLP-1, GIP, and emerging dual and triple agonists - raising the question of whether cardiovascular benefits are class-wide or molecule-specific. The conversation concludes with reflections on the off-label but growing use of GLP-1 therapy in type 1 diabetes, calls for further cardiovascular outcomes research in this population, and anticipation for more insights from DTM sessions exploring these evolving therapeutic frontiers.
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