The landscape of diabetes treatment has significantly evolved in 2025, with incretin therapies, particularly GLP-1 receptor agonists, taking center stage. Key regulatory decisions and clinical trials have highlighted their effectiveness in treating not only diabetes but also obesity, chronic kidney disease, and heart failure. This year has seen the US Food and Drug Administration (FDA) approve various incretin-based therapies, marking a turning point in the management of these interconnected conditions.
Regulatory Milestones and Clinical Advances
In January 2025, the FDA granted approval for semaglutide as a treatment for patients with type 2 diabetes and chronic kidney disease (CKD), based on the results of the FLOW trial. This trial established renal protection as a primary benefit of semaglutide, altering treatment algorithms to emphasize its significance. The hosts of the Diabetes Dialogue podcast, Diana Isaacs, PharmD, and Natalie Bellini, DNP, noted this as a substantial shift towards combination therapies for managing diabetes and CKD.
February 2025 marked the end of a global shortage of semaglutide. During this period, healthcare providers had to switch patients between various medications due to the limited supply. This shortage led to significant challenges, particularly as patients were often transitioned to lower doses of the medication. The increase in production by Novo Nordisk alleviated these pressures, allowing for more consistent treatment options.
Broadening the Scope of Incretin Therapies
March brought attention to the STRIDE trial, where semaglutide significantly improved pain-free walking distances for patients with peripheral artery disease. Isaacs and Bellini emphasized that such data reinforces the role of GLP-1 agents as important cardiometabolic therapies, particularly as walking serves as a practical measure of functional health.
The annual ADA Scientific Sessions in June unveiled a wealth of data on incretin therapies. Highlights included the GLP-1 candidate MariTide, which showed approximately 16% weight loss in early studies, and the oral GLP-1 formulation orforglipron, which successfully reduced A1c levels and weight without strict dosing timings. The dual action of Cagri-Sema (semaglutide and cagrilintide) demonstrated impressive weight loss results, further indicating the potential of combination therapies.
July’s discussions focused on the results of the SURPASS-CVOT. Although tirzepatide did not outperform dulaglutide, it achieved cardiovascular noninferiority, which is crucial for high-risk patients. The data suggested a 28% reduction in major adverse cardiovascular events, reinforcing confidence in using tirzepatide in patients with elevated cardiovascular risk.
In August, semaglutide received FDA approval for treating metabolic dysfunction-associated steatohepatitis (MASH), making it the second approved therapy for this growing concern. This approval has prompted healthcare providers to enhance screening processes and incorporate FIB-4 scoring into routine practice, highlighting the importance of GLP-1 therapies in managing metabolic liver disease.
By October, oral semaglutide gained a cardiovascular-risk-reduction indication through the SOUL trial, addressing prior concerns regarding the efficacy of oral formulations. This advancement opens new treatment avenues for patients who may prefer non-injectable options.
Despite the progress, November brought disappointment with the termination of Novo Nordisk’s oral semaglutide trial for Alzheimer’s disease due to insufficient evidence of efficacy. The hosts noted expert commentary suggesting that earlier intervention or injectable formulations might be necessary to effectively influence neurodegenerative pathways.
In conclusion, Isaacs and Bellini highlighted findings from the SURMOUNT-4 trial, which revealed that over 80% of individuals who stopped taking tirzepatide regained at least 25% of their weight loss, alongside a reversal of cardiometabolic improvements. They reiterated the message that obesity is a chronic condition requiring ongoing treatment, and the expanding benefits of incretin-based therapies in various health aspects underscore the need for sustained management strategies.
