Retatrutide

Retatrutide (LY3437943) is an investigational once-weekly subcutaneous injectable peptide that acts as a single molecule agonist at three distinct hormone receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. This triple mechanism distinguishes it from all currently approved agents — tirzepatide (Zepbound/Mounjaro) is a dual GIP/GLP-1 agonist, while semaglutide (Wegovy/Ozempic) is a GLP-1 mono-agonist. The addition of glucagon receptor agonism is theorized to increase energy expenditure alongside the appetite suppression and insulin sensitization produced by the GIP and GLP-1 arms, potentially enabling sustained metabolic activation that exceeds what dual agonists achieve.¹

Retatrutide is manufactured by Eli Lilly and Company and is being studied across a broad Phase 3 clinical trial program (the TRIUMPH program) covering obesity, type 2 diabetes, knee osteoarthritis, obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease (MASLD).

Retatrutide is being studied for weight management in adults with obesity or overweight with weight-related comorbidities, type 2 diabetes, knee osteoarthritis, and several other conditions. It is not currently available for clinical use outside of registered clinical trials.

Based on Phase 3 trial protocols, retatrutide is administered as a once-weekly subcutaneous injection with a structured dose escalation schedule. Available doses studied include 4 mg, 9 mg, and 12 mg. The 4 mg dose requires only a single escalation step, which may offer a favorable tolerability profile for patients who do not tolerate the higher doses.¹

No FDA-approved dosing schedule exists. Do not attempt to obtain or use retatrutide outside of a registered clinical trial.

Subcutaneous injection, once weekly (in clinical trials).

Not commercially available. Storage information is not applicable outside of clinical trial settings.

Based on Phase 3 clinical trial data:¹

• Gastrointestinal effects: Nausea, vomiting, diarrhea, and constipation — consistent with the incretin drug class. GI adverse events were dose-dependent and the primary cause of discontinuation.
• Dysesthesia: An unusual adverse effect not prominently seen with tirzepatide or semaglutide — tingling, burning, or altered sensation — was reported at higher rates with the 12 mg dose. Generally mild but notably higher than placebo.
• Thyroid C-cell tumors: As with all GLP-1 receptor agonists, the class effect of rodent thyroid C-cell tumors is expected to apply. The human relevance remains unknown.
• No approved formulation exists: Any product sold as "retatrutide" outside of an Eli Lilly clinical trial is not the pharmaceutical compound and has no quality, purity, or safety guarantee.
• Compounding is not applicable: Retatrutide has not been FDA-approved and therefore cannot be legally compounded under Section 503A.

Retatrutide is not FDA-approved as of May 2026 and is legally available only to participants in Eli Lilly's registered clinical trials.

Key Phase 3 data available as of May 2026:¹

TRIUMPH-1 (obesity, without diabetes, n=2,339, 80 weeks, announced May 21, 2026): - 4 mg dose: average weight loss of 47.2 lbs (19.0%) - 9 mg dose: average weight loss of 64.4 lbs (25.9%) - 12 mg dose: average weight loss of 70.3 lbs (28.3%) - At 12 mg: 45.3% of participants achieved ≥30% weight loss — a threshold historically associated with bariatric surgery - At 12 mg extended to 104 weeks (participants with BMI ≥35): average weight loss of 85.0 lbs (30.3%), suggesting continued loss without plateau - Discontinuations due to adverse events at 4/9/12 mg: 4.1%, 6.9%, 11.3% vs 4.9% for placebo

TRIUMPH-4 (obesity + knee osteoarthritis, announced December 2025): Met primary endpoints for both weight loss (up to 28.7% at 12 mg over 68 weeks) and improvements in pain and physical function.

TRANSCEND-T2D-1 (type 2 diabetes, announced March 2026): Met primary and key secondary endpoints with average A1C reductions up to 2.0% and weight loss up to 36.6 lbs (16.8%) at 40 weeks.

A regulatory submission (NDA) to the FDA is anticipated in 2026, with potential approval in 2027 pending completion of the full data package.