Retatrutide Research Evidence
The Retatrutide evidence base: trials, journals, and what the data does not yet show.
Key Findings at a Glance
- Retatrutide is the first triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously, adding a thermogenic component absent from prior incretin therapies. • Phase 2 trials showed retatrutide achieves 24.2 percent mean weight loss at 48 weeks, the most profound pharmacological weight loss ever recorded, with weight curves still declining at study end. • Despite activating the glucagon receptor, which normally raises blood sugar, retatrutide produces net glucose lowering because GLP-1 and GIP receptor effects overwhelm the glucagon component. • Retatrutide reduces liver fat by over 80 percent in NAFLD patients, exceeding the hepatic benefits seen with both semaglutide and tirzepatide and positioning it as a potential NASH breakthrough.
Trials and reviews
- TRIUMPH-1NEJM2025
-28.3% body weight @ 80wk · N=2339
- TRIUMPH-2NEJM2025
-20.8% @ 80wk at 12mg in T2D · N=1152
- DEXA sub-analyses from TRIUMPH2025
~25% of total loss is lean tissue · N=200
- Jastreboff phase 2NEJM2023
-24.2% @ 48wk @ 12mg · N=338
- SELECT (semaglutide · class precedent)NEJM2023
20% lower MACE in obese with CVD · N=17604
References
- Triple–Hormone–Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial
- Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. N Engl J Med. 2023;389:514-526.
- Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials.
- Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study
- Rosenstock J, et al. 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. Lancet. 2023;402(10401):529-544.
- Effects of retatrutide on body composition in people with type 2 diabetes. Lancet Diabetes Endocrinol. 2025.
- Tirzepatide Once Weekly for the Treatment of Obesity
- Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist. PMC. 2024.
- 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.
- Once-Weekly Semaglutide in Adults with Overweight or Obesity
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatohepatitis. Nature Medicine. 2024.
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.