- Nausea, diarrhea, constipation and vomiting are the most common retatrutide side effects. In Lilly's unpublished TRIUMPH-1 results, nausea affected 28.6% to 42.4% of people on retatrutide, versus 14.8% on placebo [3].
- Retatrutide can cause dysesthesia, a tingling or sensitive feeling in the skin. In Lilly's unpublished TRIUMPH-4 results, it affected 20.9% on the top dose versus 0.7% on placebo, and was usually mild [2].
- Most side effects rise with the dose. In TRIUMPH-1, 11.3% of people on the 12 mg dose stopped because of side effects, compared with 4.9% on placebo [3].
- Retatrutide is not FDA-approved, and Lilly plans to apply for approval in early 2027 [4]. Products sold online as "research" retatrutide are unapproved and may not contain what the label says [10, 12].
Status
Retatrutide is not FDA-approved. It is an investigational drug made by Eli Lilly and is in phase 3 trials. Lilly plans to file for FDA approval in the first quarter of 2027 [4].
It is legally available only to people in Lilly's clinical trials [3]. The FDA has sent a warning letter to at least one company selling it as 'research use only' [12].. Products sold online may not contain what the label says [10]. Status checked: October 1, 2026.
You've seen the retatrutide weight-loss headlines and want to know the downside. It is a "triple agonist" that acts on three hormone targets: GIP, GLP-1 and glucagon [1]. Most of what we know about its safety comes from Eli Lilly's own trials.
Several of the biggest results are still only in Lilly announcements, not medical journals. Read on to learn each reported side effect, how often it happened and how it compares with Zepbound® (tirzepatide) and Wegovy® (semaglutide).
What are the most common side effects of retatrutide?
The most common side effects of retatrutide are stomach and gut problems: nausea, diarrhea, constipation and vomiting. Lilly announced these rates from its 80-week TRIUMPH-1 trial of 2,339 adults with obesity or overweight and no diabetes, ahead of journal publication [3].
| Retatrutide side effect (TRIUMPH-1) | 4 mg | 9 mg | 12 mg | 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 (skin tingling) | 5.1% | 12.3% | 12.5% | 0.9% |
| Urinary tract infection | 7.5% | 8.8% | 8.4% | 5.3% |
| Stopped because of side effects | 4.1% | 6.9% | 11.3% | 4.9% |
Lilly said the types of side effects were generally consistent with other incretin-based drugs [3]. In TRIUMPH-4,decreased appetite was reported by up to 19.0% of people, versus 9.4% on placebo [2].
Does retatrutide cause hair loss, fatigue or low blood sugar?
Hair loss is not among the common retatrutide side effects Lilly had released as of September 2026. In the phase 2 trial's results on ClinicalTrials.gov (NCT04881760), fatigue affected 6 of 62 people on 12 mg, compared with 3 of 70 on placebo [6].
Two trials of people with type 2 diabetes reported no severe low blood sugar [5, 7]. With Zepbound®, hair loss affected about 5% versus 1% on placebo, more often women, and was linked to weight loss [9].
Are retatrutide side effects worse at higher doses?
Yes, most retatrutide side effects become more common as the dose goes up. In a 2023 phase 2 trial of 338 adults, published in the New England Journal of Medicine, gut side effects were dose-related and mostly mild to moderate [1].
Starting at 2 mg instead of 4 mg partly reduced them [1]. In TRIUMPH-1, people started at 2 mg a week and moved up every 4 weeks to their assigned dose [3]. In a phase 2 trial of 281 adults with type 2 diabetes, 35% on the drug had gut side effects, versus 13% on placebo [7].
The share of people who stopped because of side effects varied by trial, based on Lilly's unpublished results:
- TRIUMPH-1 (obesity): 4.1% to 11.3% on retatrutide versus 4.9% on placebo [3].
- TRIUMPH-3 (obesity and heart disease): 9.8% to 13.5% versus 4.8% [4].
- TRIUMPH-4 (obesity and knee arthritis): 12.2% to 18.2% versus 4.0% [2].
Lilly said TRIUMPH-4 stopping rates were "highly correlated with baseline BMI." They included people who felt they had lost too much weight [2].
How long do retatrutide side effects last?
Retatrutide's gut side effects usually ease over time, but no exact timeline has been published. In the TRANSCEND-T2D-1 trial of 537 adults with type 2 diabetes, published in The Lancet in 2026, they subsided as treatment went on [5]. In TRIUMPH-1, most cases of skin tingling went away during treatment [3].
What is retatrutide dysesthesia?
Retatrutide dysesthesia is an unusual skin feeling, such as tingling, burning or sensitivity to light touch. It stands out because it is rare with Zepbound® and standard-dose Wegovy®, though it is common with the new 7.2 mg Wegovy® dose [9, 11].
In Lilly's unpublished TRIUMPH-1 results, retatrutide dysesthesia affected 5.1% to 12.5% of people, versus 0.9% on placebo [3]. In TRIUMPH-4, it reached 20.9% on the 12 mg dose versus 0.7% [2].
Lilly described the skin symptoms as generally mild, and they rarely led people to stop [2].
Good to know
Dysesthesia is not unique to retatrutide. The Wegovy® label reports it in 22% of people on the new 7.2 mg dose, versus 0.3% on placebo. It rose with the dose, and 18% of affected people hadn't recovered by the trial's end [11].
Does retatrutide raise heart rate or affect the heart?
Retatrutide raised heart rate in a dose-dependent way in the 2023 phase 2 trial. The increase peaked at 24 weeks and then declined [1]. Approved drugs in this family also raise heart rate: by 1 to 3 beats per minute with Zepbound® and 1 to 4 with Wegovy® [9, 11].
Lilly's TRIUMPH-3 trial enrolled 1,949 adults with obesity and heart disease. Lilly reported heart events two ways, ahead of journal publication [4]:
- Broader five-part measure of major heart events: 44 people on retatrutide versus 52 on placebo (hazard ratio 0.82) [4].
- Narrower three-part measure (heart attack, stroke or heart-related death): 27 versus 23 (hazard ratio 1.12) [4].
These heart-event counts are too small to show a clear benefit or harm yet.
Can retatrutide cause cancer, pancreatitis or gallbladder problems?
No one knows yet whether retatrutide raises the risk of cancer, pancreatitis or gallbladder disease. The trials reported so far lasted about two years at most, which is too short to judge rare or slow risks. A 2026 BMJ review rated even its weight-loss evidence as low or very low certainty [8].
Approved drugs in the same family carry warnings for all three. Zepbound® (tirzepatide) has a boxed warning because it caused thyroid C-cell tumors in rats. Whether it does this in humans is unknown [9].
The Zepbound® label also warns about pancreatitis and gallbladder disease [9].
In the retatrutide phase 2 obesity trial's posted results, one person on 12 mg had acute pancreatitis. One person on 8 mg had an inflamed gallbladder. No one on placebo had either [6].
Related reading
- Retatrutide: what we know so far: how the triple agonist works and where trials stand.
- Zepbound® side effects: what the FDA label says and how to manage them.
- Wegovy® side effects: common effects, rare risks and when to call a provider.
- GLP-1 side effects explained: why this drug family upsets the stomach.
How do retatrutide side effects compare with Zepbound® and Wegovy®?
Retatrutide side effects are similar in type to those of tirzepatide (Zepbound®) and semaglutide (Wegovy®), with more dysesthesia. No trial has compared them directly, so the numbers below come from different studies and are only a rough guide.
| Side effect | Retatrutide 12 mg (TRIUMPH-1, unpublished) | Zepbound® 15 mg (FDA label) | Wegovy® 2.4 mg (FDA label) |
|---|---|---|---|
| Nausea | 42.4% | 28% | 44% |
| Vomiting | 25.3% | 13% | 24% |
| Dysesthesia | 12.5% | 0.4% | 2% |
| Stopped because of side effects | 11.3% | 6.7% | 6.8% |
| Heart rate change | Rose, peaked at 24 weeks (phase 2 trial) | +1 to 3 bpm | +1 to 4 bpm |
Sources: [1, 3, 9, 11].
Ozempic® (semaglutide) is FDA-approved for type 2 diabetes, not for weight loss [13]. Zepbound® and Wegovy® are both FDA-approved for weight management. Learn more on our weight loss hub.
Is retatrutide FDA-approved, and is "research peptide" retatrutide safe?
No. Retatrutide is not FDA-approved and is legally available only in Lilly's trials [3]. Versions sold online as a "research peptide" are unapproved drugs, and no one has tested their safety.
In March 2026, the FDA sent a warning letter to a company selling retatrutide labeled "research use only" [12]. The FDA also says the drug cannot be used in compounding under federal law [10]. Products like these carry risks the trials can't measure:
- Wrong substance: the vial may hold a different drug.
- No substance: it may contain none of the active ingredient.
- Wrong amount: it may contain too little or too much [10].
- Contamination: injectable products skip some of the body's natural defenses against germs and toxins [12].
Read more about the risks of research peptides. For an approved option, Zepbound® and Wegovy® are worth discussing with a provider.
When should you call a doctor about retatrutide side effects?
Call your study team or a healthcare provider if a side effect is severe or doesn't go away. If you consumed a product bought online, tell your provider exactly what you used.
Get medical help quickly for these warning signs, taken from the safety information for Zepbound® [9]:
- Severe stomach pain that won't go away: with or without vomiting, it can be a sign of pancreatitis.
- Upper stomach pain with fever or yellow skin or eyes: these can signal gallbladder problems.
- Nausea, vomiting or diarrhea that won't stop: it can lead to dehydration and kidney problems.
- A lump in your neck, hoarseness or trouble swallowing: tell a provider promptly.
- A racing heartbeat while resting: heart rate rose in retatrutide's phase 2 trial [1].
Call 911 or go to the nearest ER for chest pain, trouble breathing, fainting, or swelling of the face or throat.
Bottom line
- Gut side effects are the most common problem with retatrutide, and most rise with the dose.
- Skin tingling and a faster heart rate are the effects to watch.
- Long-term risks, including cancer, are still unknown.
- Retatrutide isn't approved. Zepbound® and Wegovy® are approved options today.
How we source this
We rely on primary sources: FDA labels, clinical trial records and peer-reviewed studies. Trial results not yet in a journal come from manufacturer announcements and are labeled as such. Read our editorial policy.
Frequently asked questions
What are the dangers of taking retatrutide?
The main known dangers of retatrutide are gut side effects, skin tingling and a higher heart rate. In Lilly's unpublished TRIUMPH-1 results, up to 11.3% of people stopped because of side effects [3].
Long-term risks aren't known yet. Online versions add the risk of a wrong or contaminated product [10, 12].
What happens when you stop taking retatrutide?
There is no published data yet on what happens when people stop retatrutide. In a Zepbound® trial, people who switched to placebo after 36 weeks regained 14% of their week-36 body weight over the next 52 weeks [9]. The same may happen with this medicine, but it hasn't been studied.
Is Ozempic® better than retatrutide?
No trial has compared Ozempic® and retatrutide directly. Ozempic® (semaglutide) is FDA-approved for type 2 diabetes, and Wegovy®, the same drug, is approved for weight management [11, 13]. A 2026 BMJ review found retatrutide may produce similar or greater weight loss than established drugs such as semaglutide, but rated that evidence low or very low certainty [8].
How long do retatrutide side effects last?
Retatrutide's gut side effects often ease over time, based on the TRANSCEND-T2D-1 trial [5]. In TRIUMPH-1, most cases of skin tingling and urinary tract infections went away during treatment [3].
When will retatrutide be approved?
Lilly plans to apply for FDA approval in the first quarter of 2027 [4]. Approval isn't guaranteed. Until then, retatrutide is legally available only to people in Lilly's clinical trials [3].
Sources
- Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., Coskun, T., Haupt, A., Milicevic, Z., & Hartman, M. L. (2023). Triple-hormone-receptor agonist retatrutide for obesity: A phase 2 trial. New England Journal of Medicine, 389(6), 514-526. https://doi.org/10.1056/NEJMoa2301972
- Eli Lilly and Company. (2025, December 11). Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial [Press release]. Retrieved September 29, 2026, from https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average
- Eli Lilly and Company. (2026, May 21). Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial [Press release]. Retrieved September 29, 2026, from https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html
- Eli Lilly and Company. (2026, July 23). Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C [Press release]. Retrieved September 29, 2026, from https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional
- Bajaj, H. S., Welch, M., Shah, P., Luna, E., Jaouimaa, F. Z., Liu, B., Liu, R., Chen, Y., Patel, H., & Bartee, A. (2026). Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): A double-blind, randomised, phase 3 trial. The Lancet, 407(10546), 2402-2413. https://doi.org/10.1016/S0140-6736(26)00967-0
- U.S. National Library of Medicine. (2023). A study of LY3437943 in participants who have obesity or are overweight (NCT04881760) [Study results]. ClinicalTrials.gov. Retrieved September 29, 2026, from https://clinicaltrials.gov/study/NCT04881760
- Rosenstock, J., Frias, J., Jastreboff, A. M., Du, Y., Lou, J., Gurbuz, S., Thomas, M. K., Hartman, M. L., Haupt, A., Milicevic, Z., & Coskun, T. (2023). 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 conducted in the USA. The Lancet, 402(10401), 529-544. https://doi.org/10.1016/S0140-6736(23)01053-X
- Nong, K., Shi, Q., Xie, X., Wang, Y., Agarwal, A., Guyatt, G. H., Zhang, H., Gao, Y., Khunti, K., Le Roux, C. W., Widyahening, I. S., Fan, Q., Liu, T., Mao, Y., Florez, I. D., Du, H., Pan, X., Zou, X., Wang, C., . . . Li, S. (2026). Comparative effects of drugs for adults with overweight or obesity: Systematic review and network meta-analysis. BMJ, 394, e372161. https://doi.org/10.1136/bmj-2026-372161
- Eli Lilly and Company. (2026). Zepbound® (tirzepatide) injection: Prescribing information (Rev. 08/2026). Retrieved September 29, 2026, from https://pi.lilly.com/us/zepbound-uspi.pdf
- U.S. Food and Drug Administration. (2026, September 1). FDA's concerns with unapproved GLP-1 drugs used for weight loss. Retrieved September 29, 2026, from https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
- Novo Nordisk. (2026). Wegovy® (semaglutide) injection and tablets: Prescribing information (Rev. 06/2026). Retrieved September 29, 2026, from https://www.novo-pi.com/wegovy.pdf
- U.S. Food and Drug Administration. (2026, March 31). Warning letter: Gram Peptides (MARCS-CMS 721806). Retrieved September 29, 2026, from https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/gram-peptides-721806-03312026
- Novo Nordisk. (2026). Ozempic® (semaglutide) injection: Prescribing information (Rev. 05/2026). Retrieved September 29, 2026, from https://www.novo-pi.com/ozempic.pdf
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