Beyond glycemic control: How incretins are changing the cardiovascular trajectories of diabetes and obesity

BACKGROUND: Diabetes mellitus is a leading global health concern. The parallel rise in obesity has exacerbated this burden, with projections suggesting over half of the adult population will be overweight or obese by 2050. Incretin-based therapies have emerged as cornerstone treatments for type 2 diabetes (T2DM), offering glycemic control alongside promising cardiovascular and renal benefits. RESULTS: This review consolidates current evidence regarding the cardiovascular effects of incretin-based medications. GLP-1 receptor agonists (GLP-1RAs) have demonstrated protective effects in preclinical models. Clinical trials show modest but consistent reductions in major adverse cardiovascular events (MACE), with additional renal benefits. Conversely, DPP-4 inhibitors display cardiovascular neutrality. Real-world studies largely support the superiority of GLP-1RAs over other glucose-lowering agents (e.g. DPP-4 inhibitors, insulin) in reducing MACE, though their benefits in heart failure (HF) with reduced ejection fraction remain limited. Recent trials in patients with obesity-related HFpEF demonstrate that GLP-1RAs and dual GIP/GLP-1 agonists significantly improve symptoms, functional status, and reduce HF events. CONCLUSIONS: While incretin therapies represent a transformative advancement in cardiometabolic care, challenges remain-including gastrointestinal side effects, adherence issues, lean mass loss and cost. As next-generation agents (e.g. triple agonists) advance, lifestyle interventions remain essential for durable, management of diabetes, obesity and associated cardiovascular conditions.