Retatrutide's most common side effects in clinical trials were gastrointestinal: nausea, diarrhea, constipation and vomiting, and they became more frequent at higher doses. The phase 3 trials also reported dysesthesia, an abnormal skin sensation, more often than on placebo. Retatrutide is an investigational drug: it isn't FDA-approved, it isn't available by prescription, and the only legal way to receive it is in a clinical trial.
Medical disclaimer: This page summarizes published and company-reported trial data for general information. It isn't medical advice, and it contains no dosing guidance. Retatrutide is not approved for any use. Talk to a licensed clinician about any weight-loss or diabetes treatment. Last reviewed September 26, 2026.
What retatrutide is
Retatrutide is Eli Lilly's once-weekly injectable that acts on three hormone receptors: GIP, GLP-1 and glucagon. That's why it's sometimes called a "triple agonist." Lilly describes it as "an investigational, once-weekly, triple hormone receptor agonist" that is "legally available only to participants in Lilly's clinical trials" (Lilly, May 2026).
Where the data comes from
The evidence is at different stages:
- Phase 2 obesity trial: peer-reviewed, published in the New England Journal of Medicine in June 2023 (Jastreboff et al.).
- TRANSCEND-T2D-1 (type 2 diabetes): presented at the American Diabetes Association meeting and published in The Lancet on June 6, 2026.
- TRIUMPH-1, -2, -3 and -4 (phase 3 obesity trials): reported in Lilly press releases. TRIUMPH-1 was also presented at the ADA meeting in June 2026 (ADA). Lilly says full results will be published in peer-reviewed journals. We didn't find a peer-reviewed TRIUMPH paper as of September 26, 2026.
Company press releases are topline summaries. Treat the phase 3 figures below as preliminary until full papers are out.
Phase 2 (NEJM, 2023)
The phase 2 trial randomized 338 adults with obesity or overweight, without type 2 diabetes, to retatrutide or placebo for 48 weeks (Lilly). Its safety findings, as summarized by PACE-CME:
- Gastrointestinal events (nausea, diarrhea, vomiting and constipation) were the most frequently reported adverse events. Lilly said they were mostly mild to moderate and usually occurred while the dose was being increased.
- Heart rate "increased in a dose-dependent [manner]" up to week 24 and declined afterward.
- Discontinuation due to adverse events occurred in 6% to 16% of participants on retatrutide.
- Serious adverse events occurred in 0% to 6% of the retatrutide groups, versus 4% on placebo.
Phase 3: TRIUMPH-1 (obesity, 80 weeks)
TRIUMPH-1 enrolled 2,339 adults with obesity or overweight and at least one weight-related condition, without diabetes. Participants were randomized to one of three retatrutide dose groups or placebo. Lilly reported these rates (May 21, 2026; AJMC):
| Side effect | Lowest dose group | Middle dose group | Highest dose group | Placebo |
|---|---|---|---|---|
| Nausea | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhea | 25.2% | 34.1% | 32.0% | 13.5% |
| Constipation | 23.8% | 25.9% | 26.1% | 10.9% |
| Vomiting | 10.6% | 22.8% | 25.3% | 4.8% |
| Dysesthesia | 5.1% | 12.3% | 12.5% | 0.9% |
| Urinary tract infection | 7.5% | 8.8% | 8.4% | 5.3% |
| Stopped due to adverse events | 4.1% | 6.9% | 11.3% | 4.9% |
Lilly described the dysesthesia as "mild to moderate" and said most urinary and neurological cases resolved during treatment. On efficacy, Lilly reported average weight loss of 19.0% to 28.3% across the dose groups at 80 weeks, versus 2.2% on placebo (efficacy estimand).
Phase 3: TRIUMPH-4 (obesity with knee osteoarthritis, 68 weeks)
TRIUMPH-4 was the first phase 3 readout, announced December 11, 2025 (Lilly). It compared two retatrutide dose groups with placebo:
- Nausea: 38.1% and 43.2% vs 10.7% on placebo
- Diarrhea: 34.7% and 33.1% vs 13.4%
- Constipation: 21.8% and 25.0% vs 8.7%
- Vomiting: 20.4% and 20.9% vs 0.0%
- Dysesthesia: 8.8% and 20.9% vs 0.7%. Lilly said these events "were generally mild and rarely led to treatment discontinuation."
- Stopped due to adverse events: 12.2% and 18.2% vs 4.0%
The discontinuation rate in the higher dose group, 18.2%, is the highest reported across the trials so far.
Phase 3: TRIUMPH-2 and TRIUMPH-3
Lilly announced these on July 23, 2026 (Lilly). TRIUMPH-2 enrolled adults with type 2 diabetes and obesity or overweight. In its highest dose group, compared with placebo, Lilly reported:
- Diarrhea: 33.6% vs 13.2%
- Nausea: 28.0% vs 8.0%
- Vomiting: 15.7% vs 4.2%
- Dysesthesia: 7.3% vs 0.7%
- Urinary tract infection: 8.0% vs 6.6%
- Stopped due to adverse events: 7.7% vs 4.9%
TRIUMPH-3 studied adults with severe obesity and established cardiovascular disease. We didn't find a detailed side-effect breakdown for it in Lilly's release.
What the pattern shows
Across the published and announced data:
- Gastrointestinal effects are the most common, and in most trials they're more frequent at higher doses. That matches the pattern seen with approved GLP-1 medicines (see semaglutide vs tirzepatide).
- Dysesthesia stands out. It was reported far more often than on placebo in every phase 3 trial with a breakdown. It's less familiar from the approved GLP-1 drugs, and full papers should say more.
- Dropout from side effects rises with dose. It reached 11.3% in TRIUMPH-1 and 18.2% in TRIUMPH-4 in the highest dose groups.
- Longer-term and rarer risks aren't settled. Trials of this size and length can miss rare events, and FDA will review the full data before any approval decision.
Regulatory status
- Not approved. Lilly says it "plans to submit" retatrutide to FDA in the first quarter of 2027 (Lilly, July 2026).
- Can't be compounded. In a March 31, 2025 letter posted by the Ohio Board of Pharmacy, FDA said retatrutide isn't a component of any approved drug and doesn't qualify for compounding exemptions (FDA letter). FDA's GLP-1 page says retatrutide "cannot be used in compounding under federal law" (FDA).
A note on "research" retatrutide sold online
Retatrutide is widely sold online as a "research peptide," sometimes under code names such as "GLP-3" (background). None of the trial data above applies to those products. They're unregulated, their contents and purity aren't verified by any regulator, and FDA says products like these "have been sold directly to consumers for human use" and are "of unknown quality and may be harmful to their health" (FDA letter). FDA has also warned companies selling retatrutide labeled "for research purposes" (FDA). Research-grade retatrutide prices and COAs at the vendors we rate are compared in retatrutide vendors, for research use only. For the trial and regulatory background, see what is retatrutide? For the wider legal picture, see are peptides legal?
Sources are linked inline. We'll update this page when the TRIUMPH trials are published in peer-reviewed journals.