Rankings / Metabolic Health

Retatrutide

Metabolic Health · GLP-1/GIP/glucagon agonist (triple)

Tier B+

Reviewed by Read Off Label · Last reviewed · How we grade

glp-1gipinvestigationalawaiting-readout
7.1 / 10
Tier B+
Ev 8 Bn 10 Sf 5

Bottom line

Read Off Label grades Retatrutide as B+ (7.1/10) based on strong evidence, very high benefit magnitude, and a med-risk safety profile.

Eli Lilly TRIUMPH-1 (May 21, 2026 topline): first Phase 3 readout in obesity, n=2,339 adults with obesity + ≥1 comorbidity (HTN/dyslipidemia/OSA/OA) but no diabetes, randomized 1:1:1:1 to retatrutide 4/9/12 mg or placebo SC weekly, 80-week primary with 104-week extension.

Typical use: Phase 2 used up to 12 mg SC weekly; Phase 3 weekly SC — Investigational.

What this is

Eli Lilly TRIUMPH-1 (May 21, 2026 topline): first Phase 3 readout in obesity, n=2,339 adults with obesity + ≥1 comorbidity (HTN/dyslipidemia/OSA/OA) but no diabetes, randomized 1:1:1:1 to retatrutide 4/9/12 mg or placebo SC weekly, 80-week primary with 104-week extension. Mean weight loss: 19.0% / 25.9% / 28.3% vs 2.2% placebo at 80wk; 30.3% (85.0 lbs) at 104wk on 12 mg. 45.3% of the 12 mg arm reached ≥30% loss (vs 0.5% placebo); 65.3% reached BMI <30. GI events dominant and dose-dependent; AE-driven discontinuation 11.3% (12 mg) vs 4.9% (placebo). Novel dysesthesia signal at 12.5% (vs 0.9% placebo). Magnitude is bariatric-surgery-tier in a non-surgical pill/injection class — previously only ~30% loss seen with sleeve gastrectomy/RYGB. Tirzepatide SURMOUNT-1 reached ~22.5% at 72wk; semaglutide STEP-1 ~14.9% at 68wk. Phase 2 (Jastreboff 2023 NEJM) reached ~24% at 48 weeks with a trajectory still descending; TRIUMPH-1 confirms the trajectory holds. No FDA filing announced as of May 21 2026. Remaining program: TRIUMPH-2 (T2D), TRIUMPH-3 (established CVD), TRIUMPH-4 (knee OA), TRIUMPH-Outcomes CVOT (NCT06383390), TRANSCEND-CKD Ph2b (n=146, baseline characteristics Oct 2025), head-to-head vs tirzepatide (NCT06662383, n=800, completion Dec 2026). TRANSCEND-T2D-1 (Lancet, Jun 6 2026; n=537, type 2 diabetes monotherapy, 40 wk): HbA1c −1.94% and weight −15.3% at 12 mg vs −0.81% / −2.6% placebo — the program's first peer-reviewed Phase 3 publication, confirming efficacy in T2D. Obesity Phase 3 (TRIUMPH-1) topline only — peer-reviewed publication pending.

Mechanism

Triple agonist: GLP-1 + GIP + glucagon receptors; glucagon arm adds energy expenditure in addition to appetite suppression

Dose & route

Phase 2 used up to 12 mg SC weekly; Phase 3 weekly SC

Citations

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Common questions

Does Retatrutide work?
Read Off Label rates the evidence for Retatrutide as Strong and the benefit magnitude as very high, producing an overall grade of B+ (7.1/10). Eli Lilly TRIUMPH-1 (May 21, 2026 topline): first Phase 3 readout in obesity, n=2,339 adults with obesity + ≥1 comorbidity (HTN/dyslipidemia/OSA/OA) but no diabetes, randomized 1:1:1:1 to retatrutide 4/9/12 mg or placebo SC weekly, 80-week primary with 104-week extension.
Is Retatrutide safe?
Retatrutide has a med risk profile in published human data. Legal status: Investigational (Phase 3). This is not medical advice — see the disclaimer.
What is the typical dose for Retatrutide?
Phase 2 used up to 12 mg SC weekly; Phase 3 weekly SC
How does Retatrutide work?
Triple agonist: GLP-1 + GIP + glucagon receptors; glucagon arm adds energy expenditure in addition to appetite suppression

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.