The Year So Far in GLP-1s: What Psychiatric Clinicians Need to Know

2026 has brought research and policy changes in GLP-1 receptor agonists, but what does this mean for psychiatry? Recap the developments so far this year with articles, videos, and podcasts below.

GLP-1 Receptor Agonists Linked to Lower Mortality, Cardiovascular Events in Serious Mental Illness

A retrospective target trial emulation using electronic health record data found that adults with serious mental illness (SMI) who initiated a glucagon-like peptide-1 receptor agonist (GLP-1 RA) had significantly lower all-cause mortality and fewer major adverse cardiovascular events than those who initiated a sodium-glucose cotransporter-2 (SGLT2) inhibitor.¹ The analysis, among the largest population-based studies of cardiometabolic therapies in SMI, matched more than 1.5 million adults 1:1 across bipolar disorder, major depressive disorder, and schizophrenia cohorts. At 4 years, mortality occurred in 4.91% of GLP-1 RA initiators with SMI versus 6.45% of SGLT2 inhibitor initiators (HR=0.76). Semaglutide and tirzepatide drove the survival benefit; older agents showed no consistent advantage. Combination therapy with an SGLT2 inhibitor plus semaglutide conferred incremental benefit over monotherapy. Investigators noted that the consistency of effect across diagnostic subgroups, including schizophrenia, suggests the association does not depend on treatment adherence or health system access alone.

GLP-1s for Treatment of Alcohol Use Disorder: Current and Future Directions

At the American Psychiatric Association annual meeting, Joji Suzuki, MD, reviewed the evolving evidence base for GLP-1) receptor agonists in substance use disorder treatment.² Suzuki traced the drug class's origin to exendin-4, a peptide isolated from Gila monster venom, through to semaglutide, tirzepatide, and the first triple agonist, retatrutide, which produces weight loss approaching 25% at 1 year. Population-level data show that patients on semaglutide have fewer alcohol use disorder (AUD)-related hospitalizations, fewer incident and recurrent AUD diagnoses, and fewer opioid overdose events, with preclinical models showing reduced self-administration of alcohol, cocaine, fentanyl, heroin, and tobacco. A randomized controlled trial of once-weekly semaglutide versus placebo in AUD adds to a previously limited evidence base of 4 completed trials. On the opioid use disorder front, Suzuki discussed brenipatide, which—if approved—would be the first new pharmacotherapy for the indication since buprenorphine. He also cautioned that delayed gastric emptying from GLP-1 RAs can alter the pharmacokinetics of concomitant medications, including lithium, warranting monitoring.

Evaluating Glucagon-Like Peptide-1 Receptor Agonists and Mental Health Outcomes

A systematic review and meta-analysis of 80 randomized, double-blind, placebo-controlled trials—including 107,860 participants with diabetes or obesity—found no increased risk of serious or nonserious psychiatric adverse events among individuals treated with GLP-1 RAs compared with placebo.³ Serious adverse events, including suicidality, major depression, and psychosis, did not differ between groups, nor did depressive symptom scores. GLP-1 RA use was associated with statistically significant improvements in restrained and emotional eating, as well as in mental health-, physical health-, diabetes-, and weight-related quality of life. Improvements in mental health-related quality of life did not correlate with weight loss, suggesting a central psychological mechanism independent of weight reduction. Cognitive outcomes, limited to 4 studies, showed no significant change. Because the analysis excluded participants with preexisting psychiatric or neurological conditions, generalizability to psychiatric populations remains limited. The authors conclude that GLP-1 RAs appear psychiatrically safe in individuals with diabetes or obesity and confer modest mental health benefits.

Podcast: The Role of GLP-1s in Psychiatry, Learning More With Roger S. McIntyre, MD, FRCPC

In this installment of "Brain Trust: Conversations in Psychopharmacology," Joseph F. Goldberg, MD, spoke with Roger S. McIntyre, MD, FRCPC, about the psychiatric relevance of GLP-1s.⁴ McIntyre described the drug class as "truly transformative," noting that its effects on the brain support classifying these agents as psychiatric drugs in practice, if not by label. Five US Food and Drug Administration indications currently cover obesity, diabetes, sleep apnea, cardiovascular disease, and kidney disease; psychiatric use, such as managing antipsychotic-associated weight gain, remains off-label. McIntyre linked obesity and impaired glucose tolerance to downstream effects on brain health that manifest as neurologic and psychiatric disease, and emphasized effects on brain plasticity, reward circuitry, and inflammation as mechanisms relevant to psychiatric care. He highlighted late-phase development of GLP-1 agents for prevention of cognitive impairment in Alzheimer disease, prevention of episodes in bipolar depression and schizophrenia, and treatment of alcohol use disorder and smoking.

FDA Issues Removal of Suicidal Behavior and Ideation Warning From GLP-1 RAs

The FDA has requested that drug application holders remove language regarding the risk of suicidal ideation and behavior from the labeling of 3 GLP-1 medications: liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound).⁵ The action follows a comprehensive FDA review that found no increased risk of suicidal ideation and behavior associated with these agents. Labeling for GLP-1 RAs approved for glycemic control in type 2 diabetes had not previously included these warnings; the change aligns messaging across indications. The decision arrives amid growing interest in the psychiatric applications of GLP-1 RAs, which exert protrophic and proplasticity effects on reward and cognitive control circuits beyond their incretin activity. Advocates, including Roger S. McIntyre, MD, FRCPC, have argued that incretin-based therapies should be made equally accessible to individuals with serious mental illness as to the general obesity population.

References

1. Kuntz L. GLP-1 receptor agonists linked to lower mortality, cardiovascular events in serious mental illness. Psychiatric Times. August 31, 2026. https://www.psychiatrictimes.com/view/glp-1-receptor-agonists-linked-to-lower-mortality-cardiovascular-events-in-serious-mental-illness

2. Walters J. GLP-1s for treatment of alcohol use disorder: current and future directions. Psychiatric Times. May 16, 2026. https://www.psychiatrictimes.com/view/glp-1s-for-treatment-of-alcohol-use-disorder-current-and-future-directions

3. Impallaria M, Leconte C, Matsneva I, et al. Evaluating glucagon-like peptide-1 receptor agonists and mental health outcomes. Psychiatric Times. May 11, 2026. https://www.psychiatrictimes.com/view/evaluating-glucagon-like-peptide-1-receptor-agonists-and-mental-health-outcomes

4. Goldberg JF, McIntyre RS. Podcast: The Role of GLP-1s in Psychiatry. Learning More With Roger S. McIntyre, MD, FRCPC. Psychiatric Times. April 24, 2026. https://www.psychiatrictimes.com/view/podcast-the-role-of-glp-1s-in-psychiatry-learning-more-with-roger-s-mcintyre-md-frcpc

5. Kuntz L. FDA issues removal of suicidal behavior and ideation warning from GLP-1 RAs. Psychiatric Times. January 13, 2026. https://www.psychiatrictimes.com/view/fda-issues-removal-of-suicidal-behavior-and-ideation-warning-from-glp-1-ras