As of November 7, 2026 · Sources: New England Journal of Medicine, ClinicalTrials.gov, Eli Lilly
Retatrutide (development name LY3437943) is an experimental drug from Eli Lilly that simultaneously activates three hormone receptors: GLP-1, GIP, and glucagon. In the Phase 3 TRIUMPH-1 trial, obese adults receiving the highest dose lost an average of 25.0% of their body weight after 80 weeks, compared to 3.9% in the placebo group [1]. Retatrutide is not yet approved as a drug.
How does Retatrutide work?
Retatrutide is a so-called triple agonist. It binds to three receptors involved in the regulation of appetite, blood sugar, and energy expenditure:
- GLP-1 receptor: It promotes glucose-dependent insulin release, slows down gastric emptying and increases the feeling of satiety.
- GIP receptor: It also enhances glucose-dependent insulin secretion and complements the GLP-1 effect.
- Glucagon receptor: It increases energy expenditure and promotes fat breakdown in the liver. This third signaling pathway is absent in Semaglutide and Tirzepatide.
The combination aims to simultaneously reduce food intake and increase energy consumption.
What do the studies on Retatrutide show?
Phase 2 study (2023)
In a phase 2 study with 338 obese adults, body weight decreased by an average of 24.2% after 48 weeks with the highest dose of 12 mg, compared to 2.1% with placebo [2]. The weight curve had not yet reached a plateau at the end of the study.
Phase 3 trial TRIUMPH-1 (2026)
TRIUMPH-1 studied 2,339 adults with obesity without diabetes over 80 weeks [1]. The mean weight change was −17.6% (4 mg), −23.7% (9 mg), and −25.0% (12 mg), compared with −3.9% in the placebo group. In addition, participants with knee osteoarthritis experienced a reduction in pain, and participants with obstructive sleep apnea experienced a reduction in the number of breathing pauses per hour [1].
Eli Lilly had preliminarily reported a weight reduction of 28.3% for the 12 mg dose in May 2026 [5]. This figure comes from a separate analysis showing what the results would have been if all participants had continued the treatment as planned. The main analysis published in the journal, covering all participants, shows 25.0% [1].
In a pre-planned extension to week 104 with 532 participants who had a BMI of at least 35 at study entry, Lilly reported an average weight reduction of 30.3% for the 12 mg dose [5]. These extension data are taken from the press release and were calculated using the same methodology as the 28.3%.
What side effects were observed?
In both studies, gastrointestinal disturbances were the most common adverse reactions [1][2]. They occurred in a dose-dependent manner and were mostly mild to moderate. In the phase 2 study, heart rate also increased in a dose-dependent manner, with a peak after 24 weeks and a subsequent decline [2].
How does Retatrutide differ from Tirzepatide and Semaglutide?
The most important difference lies in the number of activated receptors. The table shows the main results of the respective registration and phase 3 trials, evaluated across all participants:
| Active ingredient | Receptors | Average weight change | Study | Status |
|---|---|---|---|---|
| Semaglutide | GLP-1 | -14.9% after 68 weeks | STEP 1 [4] | approved |
| Tirzepatide | GLP-1, GIP | -20.9% after 72 weeks (15 mg) | SURMOUNT-1 [3] | approved |
| Retatrutide | GLP-1, GIP, Glucagon | -25.0% after 80 weeks (12 mg) | TRIUMPH-1 [1] | not approved yet |
The studies are not directly comparable because they differ in duration, dosage, and participants.
A detailed comparison of all three active ingredients.
Storage and shelf life of Retatrutide
Retatrutide is supplied as a lyophilized (freeze-dried) powder. Dry, light-protected storage at 2–8 °C is recommended. After dissolving in BAC water (bacteriostatic water), the solution should be refrigerated and used within 4 weeks.
All details are in the storage instructions.
Where can I buy Retatrutide?
Reta24 offers Retatrutide as a research peptide in strengths of 10 mg, 20 mg, 30 mg, and 40 mg. Each batch is tested by HPLC for a purity of at least 98.9%. Shipping is from Germany.
View all dosages and current prices of Retatrutide.
Sources
- Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med 2026;395:1781–1793. doi:10.1056/NEJMoa2604169 · NCT05929066
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med 2023;389:514–526. doi:10.1056/NEJMoa2301972
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205–216. doi:10.1056/NEJMoa2206038
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384:989–1002. doi:10.1056/NEJMoa2032183
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Press release, May 21, 2026. prnewswire.com
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