Glucagon-Like Peptide-1 Receptor Agonists and Incident Cardiovascular Events and Death in Treated Serious Mental Illness, Type 2 Diabetes, and Obesity.

GLP-1RA use was associated with lower risks of incident myocardial infarction at 1 and 3 years compared with nonuse in adults with SMI, type 2 diabetes, and obesity.

• Risk differences were -0.007 at 1 year and -0.010 at 3 years (all P<0.001).
• Retrospective propensity score-matched cohort of 218,043 adults in the TriNetX database across 73 health care organizations.
• Population had active antipsychotic or antidepressant medication use.

GLP-1RA use was associated with lower risks of incident heart failure at 1 and 3 years.

• Risk differences were -0.011 at 1 year and -0.018 at 3 years (all P<0.001).
• Compared GLP-1RA use versus nonuse in a propensity score-matched cohort.

GLP-1RA use was associated with lower all-cause death at 1 and 3 years, with the largest absolute risk differences among the outcomes.

• Risk differences were -0.039 at 1 year and -0.065 at 3 years (all P<0.001).
• Absolute differences for death exceeded those for MI and HF.

Use of semaglutide or tirzepatide specifically was also associated with lower risks of MI, HF, and death.

• Secondary analysis restricted to semaglutide or tirzepatide exposure.
• Associations were significant for all three outcomes (all P<0.001).
• The authors highlight these agents as particularly associated with benefit.

Findings were directionally consistent after accounting for SGLT2 inhibitor and DPP-4 inhibitor use.

• Exploratory analyses also evaluated sex and race.
• These analyses were labeled exploratory.

The authors caution that the pooled associations must be interpreted in light of SMI's clinical heterogeneity and limitations of administrative case ascertainment.

• The study is retrospective and observational, using electronic health record-based TriNetX data.
• SMI was pooled across diagnoses rather than analyzed separately.
• Case ascertainment relied on administrative codes.