What the Clinical Research Shows

Retatrutide has more human data than most compounds described on research-peptide websites, because it is being developed as a prescription medicine. The studies below are the main peer-reviewed publications to date, listed roughly in the order they appeared. Dose-group details are simplified; see the original papers for full methods.

Phase 1: Safety and Weekly Dosing

The first human studies were designed to test tolerability and how the body handles the drug. In the 12-week Phase 1b trial in type 2 diabetes (The Lancet, 2022), side effects were reported by 63% of participants receiving retatrutide, compared with 54% on placebo. These were mostly gastrointestinal. The half-life was about six days. Compared with placebo, participants in the highest-dose group lost up to about 9 kg on average in 12 weeks.

Phase 2 in Obesity (NEJM, 2023)

This 48-week trial enrolled 338 adults with obesity, or with overweight plus a weight-related condition, and no diabetes. The main findings were:

• Average weight change at 24 weeks ranged from −7.2% in the lowest-dose group to −17.5% in the highest, compared with −1.6% on placebo.
• At 48 weeks the highest-dose group averaged −24.2%, compared with −2.1% on placebo.
• In the highest-dose group, 83% of participants lost at least 15% of their body weight by week 48.
• Side effects were mainly nausea, diarrhoea, vomiting and constipation. They were dose-related, mostly mild to moderate, and less frequent with a lower starting dose.
• Heart rate rose in a dose-dependent way, peaked at 24 weeks and declined afterwards.

Phase 2 in Type 2 Diabetes (The Lancet, 2023)

In 281 adults with type 2 diabetes, HbA1c (a measure of average blood sugar) fell by up to about 2.0 percentage points after 24 weeks, compared with almost no change on placebo and −1.41 points on dulaglutide, an approved GLP-1 medicine. Body weight fell by up to about 17% at 36 weeks. No severe hypoglycaemia was reported.

Liver Fat (Nature Medicine, 2024)

A substudy of the obesity trial followed 98 participants who had fatty liver disease (MASLD) with at least 10% liver fat. At 24 weeks, liver fat fell by more than 80% on average in the two higher-dose groups. In the highest-dose group, 86% of participants reached a normal liver fat level (below 5%), compared with none on placebo. The reductions tracked weight loss and improvements in insulin sensitivity.

Body Composition (Lancet Diabetes & Endocrinology, 2025)

DXA scans in the diabetes trial showed total fat mass reductions of up to about 26% at 36 weeks. The authors reported that the share of lean mass lost relative to total weight loss was similar to other obesity treatments, which is an important question for any drug that causes large weight loss.

First Phase 3 Publication: TRANSCEND-T2D-1 (The Lancet, 2026)

This 40-week trial randomised 537 adults with type 2 diabetes that was not controlled by diet and exercise alone. HbA1c fell by 1.69 to 1.94 percentage points on retatrutide, compared with 0.81 points on placebo. Body weight fell by 11.5% to 15.3%, compared with 2.6% on placebo. Between 2% and 5% of participants on retatrutide stopped treatment because of side effects, compared with none on placebo. There was no severe hypoglycaemia.

Other Areas Under Study

• Blood lipids and inflammation: post-hoc analyses of the Phase 2 trials found reductions in apolipoprotein B, triglyceride-rich lipoproteins and, in people without diabetes, C-reactive protein.
• Kidney function: TRANSCEND-CKD, a Phase 2b study of 146 people with chronic kidney disease, measures kidney filtration and kidney fat by MRI.
• Heart tissue: laboratory studies have examined how retatrutide affects the contraction of isolated mouse and human heart muscle preparations.
• Cancer biology: a 2025 mouse study looked at obesity-related tumour growth. This is preclinical work only.

What We Still Don't Know

• Full peer-reviewed results of the TRIUMPH obesity trials had not all been published at the time of writing.
• Safety data beyond roughly 80 weeks of treatment, and in larger and more diverse populations, are still being collected.
• No direct comparison with tirzepatide or semaglutide has been published.
• It is unclear what happens to weight and metabolic markers after treatment stops.

Main Sources

1. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss. Cell Metab. 2022;34(9):1234-1247. PMID 35985340
2. Urva S, et al. LY3437943 in people with type 2 diabetes: a phase 1b multiple-ascending dose trial. Lancet. 2022;400:1869-1881. PMID 36354040
3. Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389:514-526. PMID 37366315
4. Rosenstock J, et al. Retatrutide for people with type 2 diabetes: a phase 2 trial. Lancet. 2023;402:529-544. PMID 37385280
5. Sanyal AJ, et al. Retatrutide for metabolic dysfunction-associated steatotic liver disease: a phase 2a trial. Nat Med. 2024;30:2037-2048. PMID 38858523
6. Coskun T, et al. Effects of retatrutide on body composition in type 2 diabetes. Lancet Diabetes Endocrinol. 2025;13:674-684. PMID 40609566
7. Bajaj HS, et al. Retatrutide in type 2 diabetes inadequately controlled with diet and exercise (TRANSCEND-T2D-1). Lancet. 2026;407:2402-2413. PMID 42250575
8. Giblin K, et al. Rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab. 2026;28:83-93. PMID 41090431
9. Heerspink HJL, et al. Design of the TRANSCEND-CKD trial of retatrutide. Nephrol Dial Transplant. 2026;41:1058-1068. PMID 41160422
10. Ruotolo G, et al. Retatrutide-associated improvements in cardiovascular risk biomarkers. Diabetes Obes Metab. 2026. PMID 42608321
11. Li W, et al. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discov. 2024;10:77. PMID 39019866