GLP-1 agonists

Trial registry update: COMPLETED. No results reported in the supplied registry record.

Trial registry update: RECRUITING. No results reported in the supplied registry record.

Trial registry update: NOT_YET_RECRUITING. No results reported in the supplied registry record.

Trial registry update: NOT_YET_RECRUITING. No results reported in the supplied registry record.

Trial registry update: ACTIVE_NOT_RECRUITING. No results reported in the supplied registry record.

Trial registry update: COMPLETED. No results reported in the supplied registry record.

Trial registry update: COMPLETED. No results reported in the supplied registry record.

Trial registry update: NOT_YET_RECRUITING. No results reported in the supplied registry record.

Trial registry update: RECRUITING. No results reported in the supplied registry record.

Trial registry update: RECRUITING. No results reported in the supplied registry record.

Trial registry update: ACTIVE_NOT_RECRUITING. No results reported in the supplied registry record.

Trial registry update: RECRUITING. No results reported in the supplied registry record.

This matched cohort study compared 50,009 adults with obesity and C-reactive protein levels of 3-10 mg/L who received GLP-1 receptor agonists to a similar-sized group receiving metformin, orlistat, or phentermine. Over a median follow-up of up to 3,650 days, GLP-1 exposure was associated with a 39% lower hazard of the composite outcome of all-cause mortality, myocardial infarction, and ischemic stroke, with the strongest effect on all-cause mortality (39% lower hazard). Ischemic stroke, arrhythmias, and heart failure with reduced ejection fraction showed modest reductions, while myocardial infarction and heart failure with preserved ejection fraction did not differ significantly.

Retrospective cohort study of 43,930 adults aged ≥65 years with metabolic dysfunction-associated steatotic liver disease (MASLD), comparing GLP-1 receptor agonist initiators to unexposed patients using propensity-score matching. GLP-1 RA use was associated with lower hazards of hepatic decompensation (HR 0.72), mortality (HR 0.55), and hospitalisation (HR 0.95), but showed no reduction in major adverse cardiovascular events (HR 0.98). Increased rates of gastrointestinal events, osteoporosis without fracture, and retinopathy were observed in the GLP-1 RA group.

This systematic review synthesizes evidence linking chronic low-grade inflammation (inflammaging) driven by senescent cells to concurrent skeletal aging and cognitive impairment. The authors propose that SASP-derived cytokines and inflammatory pathways (NF-κB, NLRP3) simultaneously drive bone resorption and neuroinflammation through the bone-brain axis, and discuss candidate interventions including senolytics, though they explicitly note most mechanisms rest on preclinical models or single cohorts lacking independent human validation.

The MOTIVATE study is a randomized trial protocol examining supervised exercise (3 times weekly for 32 weeks) and semaglutide treatment (weekly injections for 16 weeks), alone or combined, versus control in older adults with type 2 diabetes. The study will measure cognitive function via testing, physical outcomes, metabolic markers, and brain imaging to evaluate whether these interventions support cognitive health and physical function in this population.

A retrospective cohort study of 1.4 million adults with metabolic dysfunction-associated steatohepatitis (MASH) examined clinical outcomes in 168,733 GLP-1 receptor agonist users versus matched non-users. GLP-1 RA exposure was associated with reduced all-cause mortality (RD −0.022) and lower ascites incidence (RD −0.013), though a statistically significant but clinically negligible increase in hepatocellular carcinoma was detected (RD 0.000).

This systematic review examined pharmacological interventions targeting aging pathways, including metformin, from literature published January 2010–May 2026. Metformin and rapamycin had among the most extensive preclinical and translational evidence, but the review found that clinical evidence for broadly applicable geroprotection remains limited. The authors emphasize a substantial gap between mechanistic plausibility and clinically validated geroprotection in humans.

This systematic review synthesizes evidence on GLP-1 receptor agonists as potential geroprotective agents. Clinical trials showed: SELECT trial found 19% reduction in all-cause mortality (HR 0.81) in obese patients without diabetes; FLOW trial showed 24% reduction in primary kidney composite endpoint (HR 0.76); and a 2025 semaglutide trial demonstrated significant deceleration of three DNA methylation aging clocks (DunedinPACE, PCGrimAge, PhenoAge) over 32 weeks. Mechanistic evidence links benefits to hypothalamic GLP-1 receptor signaling, AMPK/SIRT1 pathways, and microbiome-derived short-chain fatty acids.

This prospective randomized open-label trial enrolled 66 adults with obesity who had not used weight-loss medications for at least 3 months. Participants received semaglutide, tirzepatide, or metformin for 24 weeks. The study measured changes in epigenetic (biological) age using iWatchAge DNA methylation testing and tracked aging-related biomarkers including inflammatory factors, metabolic parameters, and body composition.