Retatrutide

aka LY3437943 · Triple G

CAS 2381089-83-2C221H342N46O68

strong evidenceInvestigational

Retatrutide in brief

Retatrutide (LY3437943) is an investigational once-weekly agonist of the GIP, GLP-1 and glucagon receptors developed by Eli Lilly. In its 48-week Phase 2 trial (NCT04881760), the 12 mg arm reported a 24.2% mean body weight reduction versus 2.1% with placebo. It is not FDA-approved; four Phase 3 TRIUMPH trials have completed.

Phase 2 results by dose, with adverse events

Open any panel for the full data

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Long-form breakdowns

18 videos

Short-form clips

27 clips

Clinical trial status

The Phase 2 obesity trial (NCT04881760) randomized 338 adults for 48 weeks. Least-squares mean body weight change at 48 weeks was -8.7% (1 mg), -17.1% (4 mg), -22.8% (8 mg) and -24.2% (12 mg), against -2.1% with placebo (PMID 37366315). The Phase 2 trial breakdown has the per-arm tables.

Phase 3 trial	Registry ID	Population	Enrolled	Registry status
TRIUMPH-1	NCT05929066	Obesity or overweight	2,335	Completed, no posted results
TRIUMPH-2	NCT05929079	Obesity or overweight with type 2 diabetes	1,152	Completed, no posted results
TRIUMPH-3	NCT05882045	Obesity with cardiovascular disease	1,946	Completed, no posted results
TRIUMPH-4	NCT05931367	Obesity or overweight with knee osteoarthritis	445	Completed, no posted results

Registry data as of October 2026. Topline Phase 3 figures released by the sponsor are covered in the TRIUMPH program overview.

Sources

Full Research Data

Overview

Retatrutide is a novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Developed by Eli Lilly, it has demonstrated unprecedented weight loss results in Phase 2 trials, with participants losing up to 24% of body weight. The triple mechanism may provide superior metabolic benefits compared to dual agonists like tirzepatide.

PubMed results: 128 · Human studies: 84 · Animal studies: 87

Dosing Ranges

Ranges reflect protocols studied in published research and animal-model extrapolation. Presented for research purposes only, not a recommendation or instruction for human use.

Doses studied in published research. Information presented for research purposes only, not a recommendation for human use.

Subcutaneous Injection — standard range 1-12 mg weekly, Once weekly. Phase 3 trials ongoing

Half-Life

~6 days (high confidence)

Observed Benefits

Weight loss (Strong Phase 2 data): Phase 2 showed up to 24% weight loss at 12 mg

Side Effects

Gastrointestinal effects (nausea, vomiting, diarrhea, constipation) — Mild, Common. Phase 2 obesity trials reported GI adverse events typical of incretin-class agonists, generally mild to moderate and most frequent during dose escalation.
Decreased appetite and early satiety — Mild, Common. Appetite reduction is a expected pharmacodynamic effect of GLP-1 pathway agonism and was commonly observed alongside weight-loss endpoints in clinical studies.
Injection site reactions — Mild, Uncommon. Subcutaneous administration has been associated with local erythema or discomfort at the injection site in clinical trial reports.

Contraindications

Personal or family history of medullary thyroid carcinoma (MTC) (Established): GLP-1 receptor agonists carry class labeling based on rodent C-cell tumor findings; triple GLP-1/GIP/glucagon agonism inherits this restriction for individuals with personal or family history of MTC.
Multiple Endocrine Neoplasia syndrome type 2 (MEN2) (Established): MEN2 confers elevated MTC risk; incretin-based agents with GLP-1 activity are typically contraindicated in this setting under class labeling principles.

Storage

Lyophilized (powder): Refrigerated (2-8°C), Up to 24 months. Light sensitive: yes, store dark

Reconstituted (solution): Refrigerated (2-8°C), 4-6 weeks. Solvent: Bacteriostatic water

Clinical Trials

NCT03841630 — A Safety Study of LY3437943 Given as a Single Injection in Healthy Participants (PHASE1), status: COMPLETED. Indications: Healthy
NCT04823208 — A Study of LY3437943 in Japanese Participants With Type 2 Diabetes Mellitus (T2DM) (PHASE1), status: COMPLETED. Indications: Diabetes Mellitus, Type 2
NCT06039826 — A Study of LY3437943 in Postmenopausal Female Participants Who Are Overweight or Obese (PHASE1), status: COMPLETED. Indications: Overweight
NCT04867785 — A Study of LY3437943 in Participants With Type 2 Diabetes (PHASE2), status: COMPLETED. Indications: Type 2 Diabetes
NCT07226947 — Body Composition and Exercise to Prevent Muscle Loss With GLP1 Agonist Treatment (NA), status: RECRUITING. Indications: Obesity, Body Composition
NCT05611957 — A Study of LY3437943 in Healthy Participants and Participants With Impaired Renal Function (PHASE1), status: COMPLETED. Indications: Healthy, Renal Insufficiency
NCT06982846 — A Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia (PHASE1), status: ACTIVE_NOT_RECRUITING. Indications: Type 2 Diabetes Mellitus
NCT06808802 — To Investigate the Effect of Retatrutide (LY3437943) on Metoprolol Pharmacokinetics in Healthy Participants (PHASE1), status: COMPLETED. Indications: Healthy
NCT06313528 — A Study to Measure Calorie Consumption and Usage in Participants With Obesity Using LY3437943 (PHASE1), status: COMPLETED. Indications: Obesity
NCT07467447 — Effect of LY3437943 Versus Placebo in Participants Who Have Obesity or Are Overweight (PHASE2), status: RECRUITING. Indications: Obesity
NCT05929079 — A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight (PHASE3), status: ACTIVE_NOT_RECRUITING. Indications: Type 2 Diabetes, Obesity, Overweight, Obstructive Sleep Apnea
NCT05548231 — A Study of LY3437943 in Chinese Participants With Obesity Or Overweight (PHASE1), status: COMPLETED. Indications: Overweight, Obesity
NCT04881760 — A Study of LY3437943 in Participants Who Have Obesity or Are Overweight (PHASE2), status: COMPLETED. Indications: Obesity, Overweight
NCT05882045 — A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease (PHASE3), status: ACTIVE_NOT_RECRUITING. Indications: Obesity, Cardiovascular Diseases
NCT07035093 — A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight and Chronic Low Back Pain (PHASE3), status: RECRUITING. Indications: Obesity, Overweight, Chronic Low Back Pain (CLBP)
NCT05936151 — A Study of Retatrutide (LY3437943) on Renal Function in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes (PHASE2), status: COMPLETED. Indications: Overweight or Obesity, CKD, Type 2 Diabetes
NCT07357415 — A Study of Retatrutide (LY3437943) in Participants Without Type 2 Diabetes Who Have Obesity or Overweight (PHASE3), status: RECRUITING. Indications: Obesity, Overweight
NCT06354660 — Effect of Retatrutide Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (TRANSCEND-T2D-1) (PHASE3), status: COMPLETED. Indications: Diabetes Type 2
NCT04143802 — A Study of LY3437943 in Participants With Type 2 Diabetes Mellitus (T2DM) (PHASE1), status: COMPLETED. Indications: Diabetes Mellitus, Type 2
NCT05916560 — A Study of LY3437943 in Participants With Impaired and Normal Liver Function (PHASE1), status: COMPLETED. Indications: Healthy, Hepatic Insufficiency