Diabetes treatment is undergoing a significant transformation in 2025, primarily driven by advancements in incretin therapies. The rise of GLP-1 receptor agonists has captured attention across various medical specialties, with endocrinology leading the way in recognizing their impact. Regulatory decisions and clinical trials this year have underscored the wide-ranging applicability of these medications, particularly in diabetes management, obesity treatment, chronic kidney disease (CKD), and heart failure.
In a recent episode of Diabetes Dialogue, co-hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, reviewed the landmark developments shaping incretin-based therapies. Isaacs, a clinical pharmacist at the Cleveland Clinic, and Bellini, program director at the University Hospitals Diabetes and Metabolic Care Center, highlighted the FDA’s approval of semaglutide for patients with type 2 diabetes and CKD, a decision based on findings from the FLOW trial. This trial established renal protection as a primary benefit of semaglutide, marking a shift in treatment paradigms toward combination therapies.
The discussion also addressed the resolution of a global semaglutide shortage that persisted until February 2025. During this period, clinicians frequently switched patients between different doses due to limited supply. The decision by Novo Nordisk to increase production has alleviated these pressures, resulting in a notable decrease in reliance on compounding pharmacies.
In March, the focus shifted to the STRIDE trial, which revealed that semaglutide significantly improved pain-free walking distances in patients suffering from peripheral artery disease. The findings further solidified the role of GLP-1 agents in cardiometabolic therapies, particularly as walking serves as an accessible functional endpoint for clinical assessments.
The annual ADA Scientific Sessions in June showcased an impressive array of incretin data. Among the highlighted studies were the monthly GLP-1 candidate MariTide, which demonstrated approximately 16% weight loss in early trials, and orforglipron, an oral GLP-1 that achieved significant reductions in A1c and weight without timing constraints. Additionally, the dual amylin/GLP-1 combination, Cagri-Sema, reported over 20% weight loss in non-diabetic participants and nearly 14% in those with type 2 diabetes.
As the year progressed, the July discussion centered on the SURPASS-CVOT trial results. Although tirzepatide did not show superiority over dulaglutide, it confirmed cardiovascular noninferiority. This finding provides clinicians with increased confidence in prescribing tirzepatide for patients with elevated cardiovascular risks. Notably, pre-specified indirect comparisons suggested a potential 28% reduction in major adverse cardiovascular events (MACE) and a 39% reduction in all-cause mortality compared to a hypothetical placebo.
August brought another milestone with the FDA’s approval of semaglutide for metabolic dysfunction-associated steatohepatitis (MASH), making it the second therapy approved for this increasingly recognized condition. This approval is already prompting changes in clinical workflows, including enhanced screening and the incorporation of FIB-4 scoring to justify GLP-1 therapy for liver disease.
By October, oral semaglutide received a cardiovascular-risk-reduction indication through the SOUL trial, alleviating previous concerns regarding the cardiovascular efficacy of oral formulations. As the only available oral GLP-1 receptor agonist, the promising results from SOUL suggest potential future pathways for patients who prefer or require non-injectable treatments.
Despite these significant advances, November brought disappointing news regarding Novo Nordisk’s oral semaglutide trial for Alzheimer’s disease, which failed to demonstrate a statistically significant effect on disease progression. Experts suggest that earlier intervention or the use of injectable formulations may be necessary to influence neurodegenerative pathways, leaving room for future exploration in this area.
The episode concluded with findings from the SURMOUNT-4 trial, revealing that over 80% of individuals who withdrew from tirzepatide regained at least 25% of their prior weight loss, along with a reversal of cardiometabolic improvements. Isaacs and Bellini emphasized the critical message that obesity is a chronic disease requiring ongoing treatment. The cumulative benefits of incretin-based therapies in renal protection, cardiovascular risk reduction, liver disease, and weight management highlight the importance of long-term continuity in treatment approaches.