# Mortality in Serious Mental Illness: GLP-1 vs SGLT2 Inhibitors | This GLP A 764,115-pair emulation found four-year mortality of 4.91% vs 6.45% on GLP-1 drugs against SGLT2 inhibitors in serious mental illness, an absolute gap of 1.54 points. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/a-mortality-gap-in-serious-mental-illness Updated: 2026-09-18 Published: 2026-09-17 [← Research](https://thisglp.com/research) Evidence # Mortality in Serious Mental Illness: GLP-1 vs SGLT2 Inhibitors In people with schizophrenia, bipolar disorder or major depression, four-year mortality was 4.91% on a GLP-1 drug against 6.45% on an SGLT2 inhibitor. The one-year figure in the same paper is not believable. [This GLP Editorial Team](https://thisglp.com/about)September 20267 min readUpdated September 2026 Four-year mortality, serious mental illness · on a GLP-1 · 4.91% · on an SGLT2 inhibitor · 6.45% · HR 0.76 — a gap of 1.54 percentage points. · Both arms were on an effective drug. 195,184 matched pairs. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). ## Key takeaways - A target trial emulation matched 764,115 pairs starting a GLP-1 drug or an SGLT2 inhibitor, including 195,184 pairs with serious mental illness. - Four-year mortality in the serious mental illness cohort was 4.91% against 6.45% — a hazard ratio of 0.76 and an absolute difference of 1.54 percentage points. - A separately matched one-year analysis reported 1.46% against 2.84%, a relative risk of 0.52. - The comparator is not placebo. SGLT2 inhibitors reduce mortality themselves, so this is one effective drug measured against another. People with schizophrenia, bipolar disorder and major depression die substantially earlier than everyone else, mostly of cardiovascular disease, and that gap has resisted decades of attention. A large emulation asked whether these drugs narrow it, comparing them against SGLT2 inhibitors [\[1\]](https://thisglp.com/research/a-mortality-gap-in-serious-mental-illness#ref-1). The weight side of the same problem is covered in [clozapine weight gain and what came back](https://thisglp.com/research/do-glp1-drugs-help-antipsychotic-weight-gain). At four years, mortality among participants with serious mental illness was 4.91% on a GLP-1 drug against 6.45% on an SGLT2 inhibitor — a hazard ratio of 0.76 with an absolute risk difference of 1.54 percentage points. Among those who also had type 2 diabetes, semaglutide was associated with lower rates of major cardiovascular events, myocardial infarction, stroke and heart failure. The one-year figure is too large to believe A separately matched one-year cohort reported mortality of 1.46% against 2.84%, a relative risk of 0.52. A drug halving deaths within twelve months of the first prescription is not something any randomized trial in this class has produced over much longer periods. What that number most likely measures is that people started on a weekly injectable are, at that moment, healthier and better engaged with care than people started on a tablet. The four-year estimate is the plausible one; the one-year estimate is a warning about the method. The comparator deserves emphasis because it cuts both ways. SGLT2 inhibitors are not inert — they reduce mortality in their own right — so a margin over them is a harder thing to achieve than a margin over nothing. That makes the direction more interesting. It also means both groups were under active treatment, which removes some of the usual objection that the treated group is simply the group receiving care. Read the absolute numbers alongside the ratios, as always. A hazard ratio of 0.76 on a four-year mortality of around 6% is a gap of about one and a half people per hundred. That is a real and meaningful difference in a population with excess mortality, and it is a much smaller thing than 0.76 sounds — the same arithmetic set out in [the semaglutide and tirzepatide comparison](https://thisglp.com/research/bigger-relative-smaller-absolute) and in [the intracranial pressure meta-analysis](https://thisglp.com/research/do-glp1-drugs-help-intracranial-hypertension). The authors ask for randomized trials, which is correct and also unlikely to happen soon in this population. In the meantime the useful conclusion is narrow: there is no signal here that these drugs are dangerous in serious mental illness, which matters because psychiatric safety concerns have circulated widely around them, as [the effort and reward trial](https://thisglp.com/research/motivation-in-depression-a-secondary-finding) approaches from another direction. ## Frequently asked Do GLP-1 drugs reduce death in serious mental illness? This emulation found lower four-year mortality against SGLT2 inhibitors — 4.91% versus 6.45% — but it is observational, and the authors call for randomized trials. Why distrust the one-year result? It reports a 48% mortality reduction within twelve months of the first prescription, larger than any randomized trial of this class has produced over much longer periods. That pattern suggests the treated group was healthier when treatment started. What was the comparison drug? SGLT2 inhibitors, which reduce mortality themselves. This is not a comparison against placebo or against no treatment. ## Sources 1. \[1\] McIntyre RS, Zhang-James Y, Kwan ATH (2026). Glucagon-Like Peptide 1 Receptor Agonists, Mortality, and Cardiovascular Outcomes in Serious Mental Illness JAMA Psychiatry. [PMID 42647034](https://pubmed.ncbi.nlm.nih.gov/42647034/) ## Where to get it ### Best GLP-1 injections Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured. 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