Headline findings
All-cause mortality: HR 0.88 (95% CI 0.84-0.92) in patients on GLP-1s vs placebo or standard care. Major cardiovascular events: HR 0.86. Stroke: HR 0.90. Heart failure: HR 0.88. Dementia: HR 0.88. And the usual: -2.5% HbA1c, -14% body weight.
Methodology
The team (St Louis VA + Washington University) pooled 175 trials published between 2005 and 2024 totaling 215,970 participants and a median follow-up of 2.5 years. Semaglutide, tirzepatide, liraglutide, dulaglutide and exenatide were included.
Signals opening new doors
Unexpected reductions in non-metabolic endpoints: -11% in substance use disorders (including alcohol), -10% in opioid use disorders, -11% in suicide attempts, -10% in bacterial infections, -19% in acute hepatitis. The authors stress these are hypothesis-generating signals, not confirmed causal effects.
Risks detected
Statistically significant increases in pancreatitis (HR 1.12), low blood pressure (1.07) and nausea/vomiting (class effect). No signal of pancreatic cancer, medullary thyroid cancer or hepatotoxicity in the analyzed window.
Source: Nature Medicine
