The year 2025 has marked a significant turning point in the treatment of diabetes and related conditions, with the rise of incretin therapies, particularly GLP-1 receptor agonists. Notable advancements have emerged, including pivotal regulatory approvals and groundbreaking clinical trials that underscore the versatility of these medications across multiple health issues, such as diabetes, obesity, chronic kidney disease, and heart failure.
In a recent edition of Diabetes Dialogue, co-hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, discussed this transformative year. Isaacs serves as an endocrine clinical pharmacist and director of Education and Training in Diabetes Technology at the Cleveland Clinic, while Bellini is the program director of Diabetes Technology at the University Hospitals Diabetes and Metabolic Care Center. The discussion highlighted key moments, including the January 2025 FDA approval of semaglutide for patients with type 2 diabetes and chronic kidney disease, a decision influenced by data from the FLOW trial.
The FLOW trial established renal protection as a primary benefit of semaglutide, reshaping treatment strategies for both diabetes and kidney health. Isaacs and Bellini noted that GLP-1 receptor agonists have shown potential to slow the progression of advanced CKD, even when SGLT2 inhibitors are not viable options. This evidence marks a significant shift toward the adoption of combination therapies in clinical practice.
The conversation shifted to the end of the global semaglutide shortage in February 2025, which had forced clinicians to frequently change patients’ medications. Bellini pointed out that during the shortage, patients often had to transition between different dosages, leading to inconsistent treatment results. The decision by Novo Nordisk to increase production has since alleviated these issues, resulting in a notable decrease in reliance on compounding pharmacies.
In March, the discussion turned to the STRIDE trial, which reported that semaglutide significantly improved pain-free walking distances in patients suffering from peripheral artery disease. This trial further solidified the role of GLP-1 agents as essential tools in cardiometabolic care, particularly given the critical link between diabetes and cardiovascular health.
The June 2025 ADA Scientific Sessions delivered a wealth of information, showcasing various incretin candidates. Among them was MariTide, which demonstrated approximately 16% weight loss in initial studies, and the oral GLP-1 agent orforglipron, which achieved strong reductions in both A1c levels and weight without strict dosing timing constraints. The dual amylin/GLP-1 combination therapy, Cagri-Sema, produced an impressive weight-loss result of over 20% in non-diabetic participants and nearly 14% in those with type 2 diabetes.
As the year progressed, July brought further insights with the SURPASS-CVOT trial. While tirzepatide did not show superiority over dulaglutide, it maintained cardiovascular noninferiority, which bolstered clinical confidence in its use for patients at elevated cardiovascular risk. The trial suggested a potential 28% reduction in major adverse cardiovascular events and a 39% reduction in all-cause mortality compared to placebo.
August was another milestone month, as semaglutide received FDA approval for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). This marked a significant advancement, making it only the second approved therapy for this increasingly prevalent condition. Isaacs and Bellini discussed how this approval is altering clinical workflows by promoting broader screening and integrating FIB-4 scoring into routine evaluations.
By October 2025, oral semaglutide achieved cardiovascular-risk-reduction indications following results from the SOUL trial. This outcome alleviated longstanding concerns regarding the cardiovascular effectiveness of oral formulations, opening new treatment options for patients hesitant to use injectables. Semaglutide now stands as the only oral GLP-1 receptor agonist available, with promising results paving the way for future developments.
The year concluded with a disappointing note in November when Novo Nordisk terminated its oral semaglutide trial for Alzheimer’s disease due to a lack of statistically significant results in preventing disease progression. Despite this setback, Isaacs and Bellini highlighted expert opinions suggesting earlier intervention or the use of injectable formulations might be necessary to influence neurodegenerative pathways meaningfully.
In closing, the discussion underscored the importance of long-term treatment strategies in managing obesity, a chronic disease that demands sustained intervention. Data from the SURMOUNT-4 trial revealed that over 80% of individuals who discontinued tirzepatide regained at least 25% of their weight loss, alongside a reversal of cardiometabolic improvements. The hosts emphasized that the cumulative benefits of incretin-based therapies, including renal protection, cardiovascular risk reduction, and effective weight management, highlight a new era in diabetes care and treatment.
