Retatrutide Metabolic Research

Published literature

Retatrutide Published Literature Summary

Last Updated: August 2026

A source-linked summary of third-party retatrutide studies, including reported Phase 2 findings and sponsor-reported TRIUMPH Phase 3 results. Retatrutide remains investigational and has not been approved by a regulatory agency.

Investigational compound

Third-party study summaries

Source-specific results and limitations

Study overview

Evidence by study and endpoint

Published Phase 2 articles and sponsor-reported Phase 3 releases describe outcomes from specific trial populations, study products, dose arms, and observation periods. Each result below should be read within those source conditions.

Trial findings are specific to the cited study conditions.

The numerical findings describe the products supplied for the cited trials. They do not establish the identity, purity, safety, efficacy, or equivalence of any material sold by Precision Synthetics Canada.

28.3% Mean body-weight reduction reported at 80 weeks with 12 mg in TRIUMPH-1.

20.8% Mean body-weight reduction reported at 80 weeks with 12 mg in TRIUMPH-2.

2.0% Mean A1C reduction reported at 40 weeks in TRANSCEND-T2D-1.

Reported outcomes across study arms

Phase 3 results continued the dose-responsive pattern. TRIUMPH-1 reported up to 28.3% mean body-weight reduction at 80 weeks, while TRIUMPH-2 and TRIUMPH-3 reported up to 20.8% and 22.6% in populations with type 2 diabetes or established cardiovascular disease.

Obesity-related endpoints

TRIUMPH-1 also reported reductions in knee osteoarthritis pain and obstructive sleep apnea severity in its nested studies, extending the Phase 3 evidence beyond body weight alone.

Phase 3 glycemic control

TRIUMPH-2 reported mean A1C reductions of up to 1.6% at 80 weeks, while TRANSCEND-T2D-1 reported reductions of up to 2.0% at 40 weeks.

Pharmacology

Mechanism of action

The cited pharmacology literature describes retatrutide as an agonist at GIP, GLP-1, and glucagon receptors. Mechanistic descriptions summarize those publications and are not instructions or claims about PSC materials.

Glucagon Receptor

Published pharmacological models associate glucagon-receptor agonism with hepatic lipid metabolism and energy expenditure. The clinical contribution of each receptor cannot be isolated from these combined-agonist trials.

GLP-1 Receptor

GLP-1 receptor signaling is associated in the cited literature with glucose-dependent insulin secretion, gastric emptying, and central satiety pathways.

GIP Receptor

GIP receptor signaling is discussed in the cited literature in relation to insulin secretion and adipose-tissue metabolism. Claims about tolerability or clinical contribution require study-specific evidence.

Reported trial data

Phase 3 endpoint overview

These charts reproduce selected reported endpoints. Populations, estimands, durations, and study arms differ; the original sources control if a summary differs from a publication or release.

TRIUMPH-1 Study-Arm Outcomes

Efficacy-estimand means from baseline to week 80

Weight Outcomes Across TRIUMPH

Highest reported mean change in each pivotal trial; populations and durations differ

TRIUMPH-1 BMI Thresholds

12 mg at 80 weeks: 65.3% below BMI 30; 33.3% also reached below BMI 25

TRIUMPH-2 Glycemic Control

Mean A1C change at 80 weeks in adults with T2D and obesity or overweight

Study context

Endpoint summary

The following table summarizes the reported Phase 3 endpoints now available across the pivotal obesity and type 2 diabetes trials.

Research area	Population / window	Reported result	Study context
TRIUMPH-1	Obesity or overweight without type 2 diabetes; 80 weeks	Up to 28.3% mean body-weight reduction	At 12 mg, 65.3% of participants reached BMI below 30 and 33.3% reached BMI below 25.
TRIUMPH-2	Type 2 diabetes with obesity or overweight; 80 weeks	Up to 20.8% mean body-weight reduction and 1.6% mean A1C reduction	All three specified study arms met the primary weight endpoint in this population.
TRIUMPH-3	Severe obesity with established cardiovascular disease; 80 weeks	Up to 22.6% mean body-weight reduction	The trial included participants with or without type 2 diabetes.
TRIUMPH-4	Obesity or overweight with knee osteoarthritis; 68 weeks	Up to 28.7% mean body-weight reduction and up to 75.8% WOMAC pain reduction	Body weight and knee-pain change were co-primary endpoints.
TRANSCEND-T2D-1	Type 2 diabetes; 40 weeks	Up to 2.0% mean A1C reduction and 16.8% mean body-weight reduction	The trial met its primary and key secondary endpoints.

Study summaries

Review source-specific findings

Each panel identifies its study design, population, duration, and reported endpoints. Dose values identify trial arms and are not a protocol.

Pivotal Phase 3 results are now available

TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 each met their primary weight-related endpoints. Lilly says these results complete the clinical data package it plans to use for global regulatory submissions, with a U.S. Biologics License Application planned for the first quarter of 2027. Retatrutide remains investigational and has not been approved by a regulatory agency.

Four positive TRIUMPH trials Regulatory submission planned

Results by trial

TRIUMPH-1: Participants receiving 12 mg lost an average of 28.3% of body weight at 80 weeks. TRIUMPH-2: Participants with type 2 diabetes and obesity or overweight lost up to an average of 20.8% at 80 weeks. TRIUMPH-3: Participants with severe obesity and established cardiovascular disease lost up to an average of 22.6% at 80 weeks. TRIUMPH-4: Participants with obesity and knee osteoarthritis receiving 12 mg lost an average of 28.7% at 68 weeks, alongside improvement in the trial's knee-pain endpoint.

The broader development program continues

The pivotal trials for the initial obesity data package have reported, but not every retatrutide study is finished. TRIUMPH-5 and other Phase 3 or Phase 3b studies remain active across additional populations and outcomes.

Phase 2 obesity: 48-week data

Jastreboff, A. M., et al. NEJM (2023) ?

Design: 48-week, double-blind, randomized, placebo-controlled trial of 338 adults with BMI ≥30, or ≥27 with comorbidities. Protocol-defined study arms included amounts up to 12 mg; administration procedures are available in the publication.

Outcomes: At 48 weeks, the 12 mg dose achieved a 24.2% mean reduction in body weight. In the 8 mg and 12 mg cohorts, all participants lost at least 5% of baseline body weight, and more than one quarter of participants in the 12 mg cohort lost more than 30%.

24.2% at 48 weeks Dose-response signal Ongoing trajectory

Phase 2 type 2 diabetes

Rosenstock, J., et al. The Lancet (2023) ?

Design: 36-week trial evaluating 281 participants with T2D, comparing retatrutide with placebo and dulaglutide 1.5 mg.

Reported outcomes: The publication reported a mean HbA1c reduction of up to 2.16% in the 12 mg study arm, together with changes in body weight. Refer to the article for the estimand, confidence intervals, adverse events, and protocol details.

NAFLD/MASH-oriented endpoints

Sanyal, A. J., et al. Hepatology / EASL data ?

Design: A sub-study of the Phase 2 obesity trial focused on 98 patients with nonalcoholic fatty liver disease (NAFLD), recently updated in nomenclature to MASLD.

Reported outcomes: The sub-study reported relative liver-fat changes of 81.4% to 86.0% at 48 weeks in the 8 mg and 12 mg study arms, with approximately 89% of participants below the specified 5% threshold. The sub-study design and population limit broader interpretation.

86% liver fat reduction Normalization endpoint Hepatic lipid focus

Study methods

Protocol-controlled procedures

The cited trials used investigator-controlled study arms and escalation procedures under clinical supervision. This page does not reproduce those procedures or provide instructions for preparation, administration, amount, frequency, or escalation. Consult the original publication and registered protocol for the complete methodology.

Terminology

Glossary of terms

Incretin Hormones

Metabolic hormones (like GLP-1 and GIP) that are released from the gut into the bloodstream in response to food ingestion, helping to lower blood glucose levels by stimulating insulin release and reducing appetite.

Glucagon

A hormone traditionally responsible for raising blood sugar levels. However, in the context of co-agonism (paired with GLP-1/GIP), its activation increases energy expenditure and promotes the breakdown of fats (lipolysis), particularly in the liver.

MASLD / MASH (formerly NAFLD / NASH)

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the accumulation of excess fat in the liver. It can progress to Metabolic Dysfunction-Associated Steatohepatitis (MASH), which involves liver inflammation and damage, potentially leading to fibrosis or cirrhosis.

References & source data

Phase 2 obesity: Jastreboff, A. M., et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with obesity. The New England Journal of Medicine, 389(6), 514-526. https://doi.org/10.1056/NEJMoa2301972
Phase 2 type 2 diabetes: Rosenstock, J., et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes. The Lancet, 402(10401), 529-544. https://doi.org/10.1016/S0140-6736(23)01053-X
NAFLD/MASH sub-study: Sanyal, A. J., et al. (2024). Retatrutide in patients with non-alcoholic fatty liver disease. Hepatology. Abstract data reference
TRIUMPH and TRANSCEND Phase 3 results: Lilly announcements for TRIUMPH-1 and TRANSCEND-T2D-1, TRIUMPH-2 and TRIUMPH-3, and TRIUMPH-4. Ongoing-study context: TRIUMPH-5 (NCT06662383).