GLP-1 Drugs May Cut Death Risk in Serious Mental Illness
A new study finds GLP-1 receptor agonist drugs are linked to a 24% lower mortality risk over four years in adults with serious mental illness, primarily by
Adults with serious mental illness who started a GLP-1 drug had a 24% lower risk of death over four years compared to those starting a different diabetes medication. The research, led by Dr. Roger McIntyre of the University of Toronto and published in JAMA Psychiatry, suggests these drugs could help narrow the significant lifespan gap faced by this population.
People living with serious mental illnesses like major depressive disorder, bipolar disorder, or schizophrenia have a life expectancy roughly 10 to 25 years shorter than the general public. Cardiovascular disease is the primary driver of this excess mortality. The study authors note this results from a combination of high cardiometabolic risk, side effects of psychiatric medications, and systemic disparities in healthcare.
Study Details and Key Findings
The retrospective analysis used electronic health records to emulate a clinical trial, creating 195,184 matched pairs of patients with serious mental illness. One group initiated a GLP-1 receptor agonist, while the other started an SGLT2 inhibitor. After four years, 4.91% of the GLP-1 group had died, compared to 6.45% of the SGLT2 group-an absolute risk difference of 1.54 percentage points.
The survival benefit was dramatic within the first year, with GLP-1 initiators showing a 49% lower risk of all-cause death. "The impetus to conduct our study was provided by the observation that people living with serious mental illness... Have a significantly higher rate of mortality," Dr. McIntyre told MedPage Today. He called the drug class "potentially major in the psychiatric population."
Cardiovascular Benefits Drive Results
A closer look at patients taking the GLP-1 drug semaglutide (sold as Ozempic and Wegovy) confirmed the mortality reduction was largely driven by fewer heart-related events. The study reported significant risk reductions across multiple cardiovascular outcomes for those on semaglutide.
| Cardiovascular Outcome | Hazard Ratio (95% CI) |
|---|---|
| 3-point major adverse cardiovascular events (MACE) | 0.77 (0.76-0.79) |
| 5-point MACE | 0.76 (0.75-0.77) |
| Myocardial infarction (heart attack) | 0.71 (0.69-0.73) |
| Stroke | 0.89 (0.86-0.92) |
| Heart failure | 0.73 (0.72-0.74) |
| Coronary artery bypass grafting | 0.77 (0.70-0.85) |
The authors wrote that this pattern supports "a broad cardiometabolic benefit rather than an isolated outcome-specific signal." They theorize the drugs' anti-inflammatory and anti-atherogenic effects, along with potential impacts on behavior and risk factors like alcohol use, may underlie the protective effect.
Not All GLP-1 Drugs Showed Equal Effect
The survival advantage was not consistent across all medications in the GLP-1 class. The benefit was seen only with newer agents. At the four-year mark, significant mortality reductions were seen in patients with type 2 diabetes and serious mental illness who started semaglutide or tirzepatide (Mounjaro, Zepbound). Older drugs like dulaglutide (Trulicity) and liraglutide (Victoza, Saxenda) showed no consistent survival advantage over SGLT2 inhibitors.
Exploratory analyses over ten years indicated semaglutide was associated with lower mortality across different serious mental illness conditions, including major depressive disorder, bipolar disorder, and schizophrenia.
Limitations and Future Implications
The study authors acknowledged limitations, including an inability to fully control for medication adherence, lifestyle factors, or socioeconomic status. They also noted that cost barriers and inequities in access to GLP-1 drugs disproportionately affect people with serious mental illness, which may limit the real-world application of the findings.
Dr. McIntyre concluded the results justify considering these agents as part of integrated care for mental illness to improve health span and lifespan. The findings provide impetus for further research to understand the mechanisms behind the anti-mortality effect.
