Retatrutide
Published research and evidence base
Retatrutide (LY3437943) is an investigational single-peptide triple agonist of the GIP, GLP-1 and glucagon receptors, first described in preclinical rodent pharmacology and phase 1 studies in 2022 and subsequently in phase 2 randomised trials in obesity, type 2 diabetes and metabolic dysfunction-associated steatotic liver disease. Phase 2 reports documented dose-dependent reductions in body weight, HbA1c and liver fat content, alongside predominantly gastrointestinal adverse events. A registrational phase 3 programme (TRIUMPH-1 to TRIUMPH-4) and a separate TRANSCEND programme in type 2 diabetes and chronic kidney disease have been described in published design papers, and the first phase 3 readout (TRANSCEND-T2D-1) was published in The Lancet in 2026. As of August 2026 the compound was not an approved medicine in any jurisdiction.
- Studies cited
- 15
- Published 2023+
- 13
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- GIP/GLP-1/glucagon triple receptor agonism as a single peptide
- Dose-dependent body-weight reduction in phase 2 obesity trials
- Glycaemic control in type 2 diabetes
- Hepatic steatosis and MASLD liver fat content
- Body composition: fat mass versus lean mass partitioning
- Cardiometabolic biomarkers, lipoproteins and blood pressure
- Renal endpoints (UACR, eGFR) and the TRANSCEND-CKD mechanistic trial
- Appetite and eating-behaviour endpoints
- Gastrointestinal tolerability and dose escalation
- Phase 3 registrational programme design (TRIUMPH basket trials)
Compound identifiers
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Systematic review2026
Effect of Retatrutide, a Novel Triple Receptor Agonist, on Blood Pressure and Lipid Levels: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Simental-Mendia LE, et al. · High Blood Pressure & Cardiovascular Prevention · systematic review and meta-analysis of randomised controlled trials of retatrutide
Pooled analysis reported a reduction in systolic blood pressure (weighted mean difference -6.79 mmHg). Total cholesterol fell by 21.88 mg/dL, LDL cholesterol by 13.10 mg/dL and triglycerides by 40.90 mg/dL.
- 02Systematic review2025
Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials
Misra S, et al. · Journal of Basic and Clinical Physiology and Pharmacology · systematic review of 3 clinical trials, 691 randomised participants, mean age 54.3 years
The review reported that the 12 mg dose was associated with the largest weight reductions and metabolic changes across the included trials. Gastrointestinal events were the most frequently reported adverse effects.
- 03Human clinical2026
Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials
Giblin K, et al. · Diabetes, Obesity & Metabolism · design paper for four phase 3 randomised, double-blind, placebo-controlled trials, more than 5,800 participants
The paper described the TRIUMPH programme: TRIUMPH-1 and TRIUMPH-2 as weight-management basket trials with nested obstructive sleep apnoea and osteoarthritis protocols, TRIUMPH-3 in participants with established cardiovascular disease, and TRIUMPH-4 as a standalone knee osteoarthritis trial. It reported rationale and design only; outcome data were not included.
- 04Human clinical2026
Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease
Heerspink HJL, et al. · Nephrology Dialysis Transplantation · phase 2b mechanistic trial design paper, n=146 randomised participants with chronic kidney disease
The paper set out the design and baseline characteristics of a mechanistic trial whose primary endpoint was change in measured glomerular filtration rate by iohexol clearance from baseline to week 24. Primary outcome data were not reported.
- 05Human clinical2026
Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial
Bajaj HS, et al. · The Lancet · phase 3 double-blind randomised trial, n=537 adults with type 2 diabetes, 40 weeks
Mean change from baseline in HbA1c was -1.69% with retatrutide 4 mg versus -0.81% with placebo, with treatment differences across doses ranging from -0.88% to -1.12% (all P < 0.0001). This was the first published phase 3 readout for the compound.
- 06Human clinical2026
Retatrutide-Associated Improvements in Cardiovascular Risk Biomarkers in Adults With Obesity With or Without Type 2 Diabetes
Ruotolo G, et al. · Diabetes, Obesity & Metabolism · biomarker analyses of two phase 2 randomised, double-blind, placebo-controlled trials (36 and 48 weeks)
Non-HDL cholesterol fell by up to 26.9% and apolipoprotein B by up to 24.2%. Large triglyceride-rich lipoprotein particle concentrations declined by up to 84.4%.
- 07Human clinical2025
Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial
Coskun T, et al. · The Lancet Diabetes & Endocrinology · phase 2 body-composition substudy, n=189 adults with type 2 diabetes, 36 weeks
Total fat mass decreased 23.2% with retatrutide 12 mg, a least-squares mean difference of -18.7% versus placebo. The substudy characterised the relative contribution of fat and lean tissue to total weight change.
- 08Human clinical2025
The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and Obesity
Heerspink HJL, et al. · Kidney International Reports · post-hoc analysis of two phase 2 RCTs, n=281 (type 2 diabetes, 36 weeks) and n=338 (obesity, 48 weeks)
Urine albumin-to-creatinine ratio fell 37.0% with retatrutide 12 mg in the type 2 diabetes trial. Estimated GFR rose by 8.5 ml/min/1.73 m2 in the obesity trial.
- 09Human clinical2025
Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study
Kanu C, et al. · Diabetes, Obesity & Metabolism · phase 2 RCT patient-reported-outcome analysis, n=275 adults with type 2 diabetes, placebo and dulaglutide comparators
Higher retatrutide doses were associated with greater reductions from baseline in overall appetite, hunger and prospective food consumption. Changes in these ratings correlated with observed weight loss.
- 10Human clinical2024
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial
Sanyal AJ, et al. · Nature Medicine · phase 2a randomised, double-blind, placebo-controlled sub-study, n=98 adults with MASLD, 48 weeks
Relative liver fat content declined in a dose-dependent manner at 24 weeks: -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg) and -82.4% (12 mg) versus +0.3% with placebo. All active-dose comparisons versus placebo were reported as P < 0.001.
- 11Human clinical2023
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
Jastreboff AM, et al. · The New England Journal of Medicine · phase 2 randomised, double-blind, placebo-controlled trial, n=338 adults with obesity, 48 weeks
At 48 weeks the least-squares mean percentage change in body weight was -24.2% in the 12 mg group compared with -2.1% with placebo. Adverse events were predominantly gastrointestinal and dose-related.
- 12Human clinical2023
Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA
Rosenstock J, et al. · The Lancet · phase 2 placebo- and dulaglutide-controlled RCT, n=281 adults with type 2 diabetes, 36 weeks
HbA1c change at 24 weeks was -2.02% with retatrutide 12 mg versus -0.01% with placebo. Body weight fell 16.94% at 36 weeks in the 12 mg group compared with 3.00% with placebo.
- 13Human clinical2022
LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial
Urva S, et al. · The Lancet · phase 1b multiple-ascending-dose RCT, n=72 adults with type 2 diabetes, 12 weeks
Multiple ascending doses were administered over 12 weeks in adults with type 2 diabetes. Placebo-adjusted body-weight reduction reached -8.96 kg in the highest-dose cohort, and HbA1c fell significantly in the three highest-dose cohorts.
- 14Animal in vivo2026
Retatrutide Shows Multiple Metabolic Benefits in Diet-Induced Obese MASH Mouse and Hamster Models
Briand F, et al. · Obesity (Silver Spring) · diet-induced obese mouse and hamster models of MASH
In the mouse model retatrutide reduced body weight by 31% versus vehicle (P < 0.0001) and lowered hepatic steatosis scores. Insulin resistance measured by HOMA-IR was also reduced.
- 15Animal in vivo2022
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept
Coskun T, et al. · Cell Metabolism · in vitro receptor pharmacology plus diet-induced obese mice and rats, with a phase 1 single-ascending-dose cohort
The report characterised LY3437943 as a single peptide with balanced agonism at the glucagon, GIP and GLP-1 receptors. In obese rodents it reduced body weight and improved glycaemic control, with the effect attributed to both reduced calorie intake and increased energy expenditure.
What this evidence does not establish.
Retatrutide remains investigational and unapproved; long-term safety, cardiovascular outcome data and durability of effect after discontinuation have not been established in published peer-reviewed reports. As of August 2026 the TRIUMPH-1 to TRIUMPH-4 phase 3 obesity, sleep apnoea and osteoarthritis trials had published only rationale and design papers, with efficacy results disclosed by the sponsor as topline announcements rather than peer-reviewed publications.
Common questions about the research.
- What is retatrutide?
Retatrutide (development code LY3437943) is an investigational synthetic peptide with agonist activity at the GIP, GLP-1, and glucagon receptors. It is studied in metabolic research and remains unapproved by any regulatory authority.
- How does it differ from semaglutide and tirzepatide?
The three molecules target different receptor sets. Semaglutide is a single GLP-1 receptor agonist, tirzepatide a dual GIP/GLP-1 agonist, and retatrutide adds glucagon-receptor activity on top of GIP and GLP-1 — a triple-agonist profile described in the cited literature.
- What have the phase 2 trials of retatrutide reported?
A 48-week phase 2 randomised, double-blind, placebo-controlled trial in 338 adults with obesity reported a least-squares mean change in body weight of -24.2 percent in the 12 mg group compared with -2.1 percent with placebo. A separate 36-week phase 2 trial in 281 adults with type 2 diabetes reported an HbA1c change of -2.02 percent at 24 weeks with 12 mg versus -0.01 percent with placebo, and a 16.94 percent fall in body weight at 36 weeks against 3.00 percent with placebo. Adverse events across the programme were predominantly gastrointestinal and dose-related.
- Is retatrutide an approved medicine?
No. As of August 2026 retatrutide was not an approved medicine in any jurisdiction. A registrational phase 3 programme (TRIUMPH-1 to TRIUMPH-4) and a separate TRANSCEND programme have been described in published design papers, and the first phase 3 readout, a 40-week trial in 537 adults with type 2 diabetes, was published in 2026. Long-term safety, cardiovascular outcome data and durability of effect after discontinuation have not been established in peer-reviewed reports.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.