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Retatrutide side effects are known only from clinical trials, because retatrutide is an investigational drug with no FDA-approved label. In the phase 2 trial and the TRIUMPH phase 3 trials reported through July 2026, the most common side effects were digestive: nausea, diarrhea, vomiting, constipation and decreased appetite, and they increased with the dose. The trials also reported altered skin sensations called dysesthesia and, in phase 2, a temporary rise in heart rate. About 4% to 18% of people on retatrutide stopped because of side effects, depending on the trial and dose. This guide sets out what each trial reported.
Peptide Labs does not sell retatrutide. Most phase 3 figures below come from Eli Lilly’s topline announcements, which have not yet been fully peer reviewed. Our retatrutide profile covers the drug and its weight-loss results.
Key Takeaways
- Retatrutide is not FDA-approved; Lilly plans to apply for approval in early 2027.
- Digestive side effects were the most common and were more frequent at higher doses.
- Dysesthesia affected up to 20.9% at the highest dose in one trial and up to 12.5% in later trials.
- In phase 2, heart rate rose with the dose, peaked at 24 weeks and then declined.
- The FDA has warned sellers of "research use" retatrutide; those products are not the trial drug.
What retatrutide is
Retatrutide is a once-weekly injectable peptide from Eli Lilly that activates three hormone receptors: GIP, GLP-1 and glucagon. Tirzepatide activates the first two, and semaglutide only GLP-1. Glucagon receptor activity is thought to raise energy use, and the phase 2 researchers flagged heart rate as a finding that needs further study. For the approved drugs, see our guides to tirzepatide side effects and semaglutide vs tirzepatide.
Retatrutide side effects in the phase 2 trial
The phase 2 trial, published in the New England Journal of Medicine in 2023 and funded by Lilly, randomly assigned 338 adults with obesity or overweight to retatrutide or placebo for 48 weeks. Average weight loss reached 24.2% at the highest dose, versus 2.1% on placebo. On safety, the paper reported:
- Adverse events in 73% to 94% of the retatrutide groups, versus 70% on placebo.
- Digestive events that were dose-related, mostly mild to moderate, concentrated during dose escalation, and partly reduced by starting at a lower dose. Vomiting reached 20% in the second-highest dose groups.
- Stopping because of adverse events in 6% to 16% of people on retatrutide, versus none on placebo.
- Skin sensitivity or hyperesthesia in 7%, versus 1%; none of these events were severe.
- Heart rate rises that grew with the dose, peaked at 24 weeks and declined afterward; reported heart rhythm problems were mild to moderate.
- Serious adverse events in 4% of both groups, one case of acute pancreatitis, and no clinically significant low blood sugar.
- Liver enzyme (ALT) rises above three times normal in 1%, and no cases of medullary thyroid cancer or thyroid C-cell hyperplasia.
Side effects in the TRIUMPH phase 3 trials
Lilly has reported four TRIUMPH trials. The table shows the adverse-event discontinuation and dysesthesia rates across the retatrutide doses in each, compared with placebo.
| Trial (announced) | Who was studied | Stopped for side effects: retatrutide vs placebo | Dysesthesia: retatrutide vs placebo |
|---|---|---|---|
| TRIUMPH-4 (Dec 2025) | 445 adults with knee osteoarthritis, 68 weeks | 12.2-18.2% vs 4.0% | 8.8-20.9% vs 0.7% |
| TRIUMPH-1 (May 2026) | 2,339 adults without diabetes, 80 weeks | 4.1-11.3% vs 4.9% | Up to 12.5% vs 0.9% |
| TRIUMPH-2 (Jul 2026) | 1,152 adults with type 2 diabetes, 80 weeks | 3.8-11.6% vs 4.9% | 4.5-7.3% vs 0.7% |
| TRIUMPH-3 (Jul 2026) | 1,949 adults with severe obesity and heart disease, 80 weeks | 9.8-13.5% vs 4.8% | 6.4% vs 1.3% |
The highest rates came from TRIUMPH-4, the first phase 3 readout. Lilly noted lower discontinuation among participants who started with a BMI of 35 or more: 8.8% and 12.1%, versus 4.8% on placebo. Later trials reported lower dysesthesia and discontinuation rates. Because the trials enrolled different people for different lengths of time, their numbers should not be compared directly. The same caution applies to approved drugs: in Zepbound’s weight trials, 4.8% to 6.7% stopped because of side effects versus 3.4% on placebo, but those trials tested a different drug in different people, so they are context rather than a head-to-head comparison. Our Zepbound side effects guide has the label detail.
Digestive side effects
Every trial listed digestive events as the most common. Examples from Lilly’s announcements, showing the range across doses versus placebo:
- TRIUMPH-1: nausea 28.6% to 42.4% versus 14.8%; vomiting 10.6% to 25.3% versus 4.8%.
- TRIUMPH-2: diarrhea 27.4% to 33.6% versus 13.2%; nausea 13.7% to 28.0% versus 8.0%; decreased appetite 5.8% to 17.1% versus 4.5%.
- TRIUMPH-3: diarrhea 24.4% to 30.1% versus 8.7%; nausea 21.7% to 22.4% versus 5.8%; constipation 15.7% to 18.0% versus 7.1%.
- TRIUMPH-4: nausea 38.1% to 43.2% versus 10.7%; vomiting about 20% to 21% versus none.
Dysesthesia: the skin-sensation signal
Dysesthesia is an abnormal sense of touch in which ordinary contact feels tingly, burning or painful. Some news coverage called it a new signal in phase 3, but the phase 2 paper had already reported skin sensitivity in 7% of people on retatrutide. Lilly described the phase 3 events as generally mild to moderate, with most resolving during treatment. The effect is not unique to retatrutide: the Wegovy label reports dysesthesia in 22% of people on its highest dose, which suggests it may relate to high drug exposure in this class. See our Wegovy side effects guide for that data.
Heart rate, infections and unanswered questions
The phase 3 announcements did not report heart rate results, so the phase 2 finding remains the main published data point. TRIUMPH-2 and TRIUMPH-3 reported urinary tract infections slightly more often at higher doses than on placebo, 8.0% versus 6.6% and 7.0% versus 5.3% at the highest dose. Longer-term questions, such as effects on muscle, bone and heart outcomes, will depend on full publications and ongoing trials.
No approved label, and why that matters
Lilly has said it plans to submit retatrutide to the FDA in the first quarter of 2027. Until approval, there is no prescribing information, boxed warning determination or Medication Guide. The FDA states that retatrutide cannot be used in compounding and has not been found safe and effective for any condition. In a March 31, 2026 warning letter and in letters dated August 24, 2026 to five online sellers, the agency acted against retatrutide sold as “research use only” or “not for human consumption.” The trial safety data above do not apply to those products, whose content and purity are unknown. Our guide to peptides for weight loss explains where retatrutide sits among approved and investigational options.
Frequently Asked Questions
What are the most common side effects of retatrutide?
Digestive events: nausea, diarrhea, vomiting, constipation and decreased appetite. They were more frequent at higher doses and mostly mild to moderate.
What is dysesthesia on retatrutide?
An altered skin sensation, such as tingling, burning or sensitivity to touch. It was reported in up to 20.9% of people in TRIUMPH-4 and up to 12.5% in later trials, versus about 1% on placebo.
Does retatrutide raise heart rate?
In phase 2, heart rate rose with the dose, peaked at 24 weeks and then declined. Phase 3 heart rate data had not been published as of September 2026.
How many people stopped retatrutide because of side effects?
Between 3.8% and 18.2% across phase 3 trials and doses, versus about 4% to 5% on placebo.
Is retatrutide FDA-approved?
No. It is investigational. Lilly plans to seek FDA approval in early 2027.
Are online retatrutide products safe?
Their safety is unknown. The FDA has warned sellers of research-labeled retatrutide, and the trial data do not apply to those products.
This article is general information, not medical advice. Peptide Labs does not sell prescription drugs or investigational drugs such as retatrutide. Because retatrutide is not approved, there is no Medication Guide for it yet; for any GLP-1 medicine you are prescribed, read its Medication Guide and ask a pharmacist or prescriber how the information applies to you.
Last reviewed September 2026.