Study wrapper · #1288
Glucagon-Like Peptide 1 Receptor Agonists, Mortality, and Cardiovascular Outcomes in Serious Mental Illness.
Editor's note
A target-trial emulation in JAMA Psychiatry using a new-user, active-comparator design, which is the right choice for observational data of this kind, and a direction consistent with randomized cardiovascular results for semaglutide. The one-year mortality gap, close to a halving, is larger than any randomized trial has produced and points to residual confounding in who is started on which drug rather than a clean pharmacological effect. The semaglutide and tirzepatide findings sit in exploratory subgroups, not the prespecified primary outcome, and the authors themselves call for randomized confirmation.
Plain-language abstract
Researchers used a multinational health-records network to compare adults starting a GLP-1 receptor agonist with adults starting an SGLT2 inhibitor, matching the groups on age, sex and health history. Among people with serious mental illness, deaths over four years were lower in the GLP-1 group (4.91% versus 6.45%), and heart attacks, strokes and heart failure were also less frequent. The authors report the largest absolute differences in this group, driven mainly by semaglutide and tirzepatide.