Semaglutide has the most long-term data, with clinical trial follow-up extending to about 2-3 years (STEP trials, SELECT trial). Liraglutide (an earlier GLP-1 agonist) has over a decade of post-market data. Tirzepatide is newer with shorter-duration trial data (SURMOUNT trials, ~72 weeks). Real-world use of GLP-1 agonists for diabetes began in 2005 with exenatide, so the drug class has about 20 years of clinical experience overall. No major unexpected long-term safety signals have emerged for the class, but individual drugs vary.