Three generations of GLP-1 class drugs, three different receptor profiles, and vastly different efficacy. Mechanism, weight loss data, cardiovascular outcomes, side effects, and who each drug is actually right for.
Five years ago, this comparison didn't exist. The GLP-1 drug class consisted of semaglutide and liraglutide, one was clearly superior, and the clinical question was whether GLP-1 agonists were really worth the cost and injection burden. Then tirzepatide arrived in 2022 with a dual GLP-1/GIP mechanism and weight loss results that exceeded everything before it. Then Phase 2 data for retatrutide dropped in 2023 with a triple GLP-1/GIP/glucagon mechanism and weight loss numbers that exceeded tirzepatide.
In two years, the ceiling of what a single drug can do for metabolic health moved from 15% to 24%. That is a remarkable and fast-moving clinical landscape.
The fundamental difference between these three drugs is their receptor specificity. Understanding this determines everything else — efficacy, mechanism, side effects, and which patients benefit most.
| Drug | GLP-1 | GIP | Glucagon | Status |
|------|-------|-----|----------|--------|