GLP‑1 receptor agonists cut deaths in diabetic PAD patients yet raise psychiatric risk

A large observational study of more than 2,000 adults with type‑2 diabetes and peripheral artery disease (PAD) found that use of GLP‑1 receptor agonists (GLP‑1 RAs) was associated with a 26% reduction in all‑cause mortality, a 13% drop in hospitalizations and up to a 48% decline in amputations compared with metformin users. The benefits were strongest among patients with severe PAD and a body‑mass index of 30 kg/m² or higher, while rates of heart attack, stroke and serious kidney events were similar between groups.

In a separate U.S. claims‑data analysis of 8,143 patients, initiation of GLP‑1 RAs was linked to a 48% higher hazard of any psychiatric event versus DPP‑4 inhibitors or SGLT2 inhibitors. Specific risks included major depressive disorder (HR 1.55) and anxiety disorder (HR 1.58). Agent‑specific signals showed dulaglutide and liraglutide associated with depression and anxiety, exenatide with depression and suicide‑related outcomes, and semaglutide with anxiety. The two studies highlight contrasting cardiovascular/limb benefits and potential mental‑health safety signals, underscoring the need for clinicians to balance these effects when prescribing GLP‑1 RAs.