What Is Retatrutide?
Retatrutide (LY3437943) is a once-weekly injectable peptide compound under development by Eli Lilly. Unlike Semaglutide (which targets one receptor) or Tirzepatide (which targets two), Retatrutide is a triple agonist — it activates GLP-1, GIP, and glucagon receptors simultaneously. That additional glucagon pathway is what sets it apart in the research literature and why it has attracted significant clinical interest.
Phase 2 results published in the New England Journal of Medicine in June 2023 showed body weight reductions that, at the highest doses, exceeded any previously reported figures for a weight loss drug in clinical trials. Phase 3 trials (the TRIUMPH series) are now underway.
How the Triple Agonist Mechanism Works
The glucagon component matters because it adds a separate dimension to fat loss: instead of only reducing calories in (via appetite suppression), it also increases the rate at which the body burns energy at rest. Research suggests this dual action — less in, more out — accounts for the superior weight loss figures seen in Retatrutide trials compared to GLP-1 and dual GLP-1/GIP agents.
Phase 2 Clinical Trial Data
The pivotal Phase 2 trial (NCT05019444, Jastreboff et al., NEJM 2023) enrolled 338 adults with obesity (BMI ≥30 or ≥27 with weight-related comorbidity) and ran for 48 weeks. Participants without type 2 diabetes were included in the primary cohort. All doses were administered once weekly via subcutaneous injection.
| Dose | Weight Loss at 24 Weeks | Weight Loss at 48 Weeks | Notes |
|---|---|---|---|
| Placebo | −2.1% | −2.1% | |
| 1 mg | −7.2% | −8.7% | |
| 2 mg | −10.4% | −12.9% | |
| 4 mg | −14.1% | −17.3% | |
| 8 mg | −15.7% | −17.5% | |
| 12 mg | −17.5% | −22.8% | Highest dose; ongoing reduction at 48 weeks — curve not plateaued |
Source: Jastreboff AM et al., N Engl J Med 2023;389:514-526. Mean % change in body weight, intention-to-treat analysis. Primary cohort without T2D.
Key finding: At 48 weeks, the weight loss curve for the 12mg group was still declining — it had not reached a plateau. This suggests longer-term trials may produce higher figures. Phase 3 trials run to 72–96 weeks for this reason.
Retatrutide vs Semaglutide vs Tirzepatide
Direct head-to-head trials between these compounds do not exist yet. The comparison below draws on each compound's own pivotal trial data. Methodology, population, and duration differ, so comparisons should be treated as approximate.
| Compound | Receptors | Pivotal Trial | Max Weight Loss | Duration | Status |
|---|---|---|---|---|---|
| Semaglutide 2.4mg Ozempic / Wegovy |
GLP-1 | STEP-1 | 14.9% | 68 weeks | Approved (EU/Ireland) |
| Tirzepatide 15mg Mounjaro / Zepbound |
GLP-1 + GIP | SURMOUNT-1 | 22.5% | 72 weeks | Approved (EU/Ireland for T2D) |
| Retatrutide 12mg LY3437943 |
GLP-1 + GIP + Glucagon | Phase 2 NCT05019444 | 22.8% (48 wk, curve still declining) | 48 weeks | Phase 3 (TRIUMPH trials) |
Important caveat: each trial used different populations, selection criteria, and follow-up durations. This is not a controlled comparison.
Side Effects Observed in Phase 2
The adverse event profile was consistent with the GLP-1 class — the same broad category as Ozempic and Mounjaro:
- Nausea — most common, particularly during dose escalation phases
- Vomiting and diarrhoea — dose-dependent; more frequent at 8mg and 12mg
- Decreased appetite — expected mechanism; reported as a side effect by some participants
- Injection site reactions — mild, consistent with other subcutaneous injectables
- Discontinuation rate — higher at 12mg vs lower doses; manageable with slower titration protocols in Phase 3
The Phase 3 TRIUMPH trials are using slower dose escalation schedules to reduce GI adverse events, which was a lesson taken directly from the Phase 2 data.
Where Research Stands in 2026
Phase 2 results published in NEJM. Immediately became one of the most-cited obesity trial publications of the year.
TRIUMPH-1, TRIUMPH-2, and TRIUMPH-3 Phase 3 trials initiated. Broader populations including people with type 2 diabetes and cardiovascular risk.
Phase 3 data readout expected. Eli Lilly targeting regulatory submission to FDA and EMA based on trial timelines.
Potential EU/Irish regulatory approval. Subject to Phase 3 results meeting endpoints and regulatory review timelines.
Research Updates
New data will be added to this section as Phase 3 trial results are published. Last review: July 2026.
- July 2026: No Phase 3 data published yet. TRIUMPH trials ongoing. No change to Phase 2 conclusions.