The trial record
Every number on this site traces to a registered trial. Here is the retatrutide evidence base, with registry links:
| Trial | Registry | Population | Doses | Key result |
|---|---|---|---|---|
| Phase 2 obesity (Jastreboff, NEJM 2023) | NCT04881760 | 338 adults, obesity or overweight | 1 to 12 mg weekly | -24.2% at 48 wk (12 mg) |
| TRIUMPH-1, Phase 3 pivotal | NCT05929066 | 2,339 adults, obesity or overweight + comorbidity | 4, 9, 12 mg weekly | Topline: -28.3% mean at 12 mg; 45.3% lost ≥30% |
| TRIUMPH-3, obesity + CVD | NCT05882045 | Obesity with cardiovascular disease | Phase 3 | Ongoing |
| TRIUMPH-4, knee osteoarthritis | NCT05931367 | Obesity or overweight with knee OA | Phase 3 | Ongoing |
| MASLD, Phase 2a (Nature Medicine) | PMC11271400 | Metabolic liver disease | Phase 2a | Large liver-fat reductions |
How the triple agonist works
Semaglutide activates one incretin receptor (GLP-1). Tirzepatide added a second (GIP). Retatrutide adds a third - the glucagon receptor - which in trial data appears to raise energy expenditure rather than only suppressing appetite. That mechanistic addition is the best current explanation for why its Phase 2 weight-loss curve had not plateaued at 48 weeks, unlike its predecessors' at comparable timepoints.
Frequently asked questions
What is retatrutide?
Retatrutide (LY3437943) is an investigational once-weekly injectable developed by Eli Lilly that activates three receptors - GIP, GLP-1, and glucagon. In Phase 2, it produced up to 24.2% mean weight reduction at 48 weeks, the largest reported for any anti-obesity drug at that stage. It is not FDA-approved.
Is retatrutide a GLP-1?
Partly. GLP-1 agonism is one of its three mechanisms, alongside GIP (like tirzepatide) and glucagon-receptor agonism, which is the novel addition - associated with increased energy expenditure, not just reduced intake. That triple action earned it the 'GLP-3' nickname, which is marketing shorthand, not chemistry.
When will retatrutide be available?
Phase 3 (TRIUMPH) is ongoing; Lilly has signaled a regulatory submission around early 2027, which puts a plausible FDA decision in 2027-2028 if trials read out positively. No date is guaranteed. Anything available before approval is either a clinical trial or an illegitimate product.