Semaglutide vs tirzepatide

In SURMOUNT-5, the only trial to test them against each other, tirzepatide produced greater average weight loss than semaglutide over 72 weeks: −20.2% versus −13.7%, at maximum tolerated doses. The structural difference is that semaglutide acts on one receptor, GLP-1, while tirzepatide acts on two, GLP-1 and GIP. Both are FDA-approved for weight management, both are once-weekly injections, and both carry the same boxed warning and the same gastrointestinal side-effect profile. Larger average weight loss is not the same as the better choice for a given person — tolerance, cost, insurance coverage and medical history decide that, and none of them appear in a trial result.

SURMOUNT-5 reports a group average, and individual results vary widely around it — a 6.5-point mean difference tells you nothing about which drug will suit you specifically. It is a single trial, run over 72 weeks, so it says nothing about longer-term outcomes, and both drugs are for chronic use where weight is typically regained after stopping. The trial does not settle the questions that most often decide the choice in practice: cost, insurance coverage, supply, and how well you tolerate the escalation. It also enrolled adults with obesity or overweight without diabetes, so it does not describe outcomes in people with type 2 diabetes. Neither drug is a decision you make from a web page — both are prescription medicines with a boxed warning, and both are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Compounded versions of either, obtained outside the approved supply chain, are not the products these trials tested.