Adults with serious mental illness (SMI) have a shorter lifespan than the general population, primarily driven by cardiovascular disease.GLP-1 initiators had a 24% lower 4-year mortality risk than SGLT2 users in a trial emulation of adults with SMI.Benefits were largely driven by lower cardiovascular risks and were seen only with newer GLP-1 agents.
Starting a GLP-1 receptor agonist was associated with significantly lower risks of death and cardiovascular events in adults with serious mental illness (SMI), a target trial emulation showed.
Among 195,184 propensity score-matched pairs of adults with SMI, GLP-1 drug initiators had a 24% lower 4-year mortality risk compared with SGLT2 inhibitor initiators (HR 0.76, 95% CI 0.74-0.78). Death occurred in 4.91% and 6.45% of groups, respectively, equating to an absolute risk difference of -1.54 percentage points.
At year 1, all-cause mortality risk was 49% lower among GLP-1 initiators compared with SGLT2 inhibitor initiators (HR 0.51, 95% CI 0.49-0.53, P<0.001), Roger McIntyre, MD, of the University of Toronto, and colleagues reported in JAMA Psychiatry.
This association persisted across sensitivity analyses. A review of semaglutide (Ozempic, Wegovy) initiators who had SMI and type 2 diabetes indicated that the relationship was largely driven by risk reductions in cardiovascular outcomes (all P<0.001):3-point major adverse cardiovascular events (MACEs): HR 0.77, 95% CI 0.76-0.795-point MACEs: HR 0.76, 95% CI 0.75-0.77Myocardial infarction: HR 0.71, 95% CI 0.69-0.73Stroke: HR 0.89, 95% CI 0.86-0.92Heart failure: HR 0.73, 95% CI 0.72-0.74Coronary artery bypass grafting: HR 0.77, 95% CI 0.70-0.85
