Where these numbers come fromPercentages are the share of trial participants who reported each event at any time during the study. They come from published trial papers and Eli Lilly announcements. They show what happened under medical supervision, with careful dose escalation.
Side effects in TRIUMPH-1 (phase 3)
TRIUMPH-1 is the largest retatrutide trial so far: 2,339 adults with obesity, treated for 80 weeks at 4, 9 or 12 mg.[1][2]
| Event | 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 | 5.1% | 12.3% | 12.5% | 0.9% |
| Stopped due to side effects | 4.1% | 6.9% | 11.3% | 4.9% |
Side effects in TRIUMPH-4 (phase 3)
TRIUMPH-4 studied 445 adults with obesity and knee osteoarthritis for 68 weeks.[5][3]
| Event | 9 mg | 12 mg | Placebo |
|---|---|---|---|
| Nausea | 38.1% | 43.2% | 10.7% |
| Diarrhea | 34.7% | 33.1% | 13.4% |
| Constipation | 21.8% | 25.0% | 8.7% |
| Vomiting | 20.4% | 20.9% | 0.0% |
| Dysesthesia | 8.8% | 20.9% | 0.7% |
| Stopped due to side effects | 12.2% | 18.2% | 4.0% |
Lilly said that discontinuations in this trial included people who stopped because of "perceived excessive weight loss", and that rates were lower in people with a starting BMI of 35 or more (12.1% on 12 mg).[5] The NEJM paper also reported that serious adverse events were more common with retatrutide than with placebo.[3]
Side effects in the phase 2 trial
| Event | 12 mg | All retatrutide arms | Placebo |
|---|---|---|---|
| Nausea | 45% | 14–60% | 11% |
| Vomiting | 19% | 3–26% | 1% |
| Diarrhea | 15% | 9–20% | 11% |
| Constipation | 16% | 6–16% | 3% |
| Stopped due to side effects | 16% | 6–16% | 0% |
The highest rates were in the arms that started at 4 mg. The authors noted that stomach side effects were "partially mitigated with a lower starting dose (2 mg vs. 4 mg)".[6]
Side effects of retatrutide in the other phase 3 trials
The other completed phase 3 trials show the same pattern: more people stopped treatment on retatrutide than on placebo, and dysesthesia appeared in every program. Figures are the latest published as of November 13, 2026.
| Trial (date reported) | Population | Stopped due to side effects | Dysesthesia |
|---|---|---|---|
| TRIUMPH-2 (Lancet, Sep 2026)[9] | Obesity + type 2 diabetes | 3.8% / 11.6% / 7.7% (4/9/12 mg) vs 4.9% placebo | 4.5% / 5.6% / 7.3% vs 0.7% |
| TRIUMPH-3 (Lilly, Jul 2026)[10] | BMI ≥35 + heart disease | 9.8% / 13.5% (9/12 mg) vs 4.8% placebo | Not reported in topline |
| TRANSCEND-T2D-1 (Lancet, Jun 2026)[11] | Type 2 diabetes | 2–5% vs 0% placebo | Not reported in abstract |
| TRANSCEND-T2D-2 (Lilly, Oct 2026)[12] | Type 2 diabetes, vs semaglutide | 4.8% / 7.9% (9/12 mg) vs 2.7% semaglutide | 4.8% / 6.5% vs 2.7% |
No severe low blood sugar was reported in TRANSCEND-T2D-1.[11] Trials in people with diabetes generally showed lower dysesthesia rates than the obesity-only trials.
Skin sensitivity (dysesthesia)
A burning or abnormal skin sensation, which Lilly calls dysesthesia, stands out in the retatrutide trials. It rose with dose, from 5.1% on 4 mg to 12.5% on 12 mg in TRIUMPH-1 (0.9% on placebo), and reached 20.9% on 12 mg in TRIUMPH-4. Most cases were mild to moderate and rarely led to stopping.[1][5][8] Every trial's rates are on retatrutide skin sensitivity.
Heart rate
Heart rate rose with dose in phase 2, peaked around week 24 and then eased, and rhythm events were reported in 11% of people on 12 mg against 3% on placebo.[6] Blood pressure and heart-outcome data are on retatrutide heart rate and blood pressure.
Does retatrutide cause muscle loss?
The one published body-scan study found that most of the weight lost was fat. In a phase 2 substudy of people with type 2 diabetes, DXA scans showed total fat mass falling 23.2% on 12 mg and 26.1% on 8 mg over 36 weeks, against 4.5% on placebo. The authors reported that the share of weight lost as lean tissue was similar to other obesity treatments.[14]
- Lean mass includes water and organs, so it is not the same as muscle. The study did not measure muscle strength.
- Only 103 people completed both scans, all with type 2 diabetes.[14]
- No phase 3 body-composition results had been published as of November 13, 2026.
Fatigue, hair loss and other questions
| Question | What the published data show |
|---|---|
| Retatrutide fatigue | Not among the most common events in the published trial results or Lilly announcements; specific rates have not been reported in those summaries |
| Retatrutide hair loss | Not reported in the trial summaries we reviewed; no rate is available |
| Retatrutide nausea | The most common side effect: 28.6% to 42.4% across doses in TRIUMPH-1 vs 14.8% on placebo[1] |
| Retatrutide pancreatitis | One case in the 48-week phase 2 obesity trial[6]; pancreatitis is a warning on the labels of approved drugs in this class[15] |
| Serious adverse events | More common than on placebo in TRIUMPH-4: 14 people on 9 mg and 16 on 12 mg; one death in each retatrutide group, judged unrelated by investigators[4] |
"Not reported" means the published summaries are silent, not that the effect never happened. Full tables in the journal supplements may contain more.
Warnings that apply to this drug class
Retatrutide has no FDA label yet. For context, the label of tirzepatide (Zepbound), an approved drug in the same family, carries these warnings:[15]
- A boxed warning about thyroid C-cell tumors, seen in rodents. These drugs are not used in people with a personal or family history of medullary thyroid carcinoma or MEN 2.
- Pancreatitis and gallbladder disease.
- Kidney injury from dehydration after vomiting or diarrhea.
- Low blood sugar when combined with insulin or sulfonylureas.
- Serious allergic reactions, and risk of inhaling stomach contents under anesthesia.
In the phase 2 obesity trial there was one case of pancreatitis and three gallbladder-related events, and no medullary thyroid cancer.[6]
Stopping because of side effects: retatrutide vs tirzepatide and semaglutide
More people stopped retatrutide 12 mg because of side effects than stopped tirzepatide or semaglutide in their main obesity trials. These are separate trials with different lengths, so treat the comparison as rough:
| Drug and trial | Top dose | Placebo | Length |
|---|---|---|---|
| Retatrutide 12 mg, TRIUMPH-1[1] | 11.3% | 4.9% | 80 weeks |
| Tirzepatide 15 mg, SURMOUNT-1[16] | 6.2% | 2.6% | 72 weeks |
| Semaglutide 2.4 mg, STEP 1 (stomach side effects only)[17] | 4.5% | 0.8% | 68 weeks |
The direct comparison with tirzepatide, TRIUMPH-5, has not reported yet. See retatrutide vs tirzepatide.
Who was left out of the trials
Retatrutide has no label, so there is no official list of who should not use it. The closest published guide is who the trials excluded. TRIUMPH-1 did not enroll people with:[18]
- Diabetes (studied separately, in TRIUMPH-2 and the TRANSCEND trials)
- A personal or family history of medullary thyroid carcinoma or MEN 2
- A history of pancreatitis
- Past or planned obesity surgery
- A weight change of more than 5 kg, or use of any weight-loss medicine, in the previous 90 days
These were rules for a research study. They show who was not studied, not who could safely take the drug.
Is retatrutide safe?
Retatrutide's safety has not yet been judged by any regulator, because no application has been reviewed. What the trials show so far, up to 104 weeks of treatment:
- Common effects are mostly digestive and dose-related. Nausea, diarrhea, constipation and vomiting rose from the 4 mg to the 12 mg dose.[1]
- Serious adverse events were more frequent than on placebo in TRIUMPH-4, according to the NEJM paper published on November 8, 2026.[3]
- Heart outcomes are not settled. In TRIUMPH-3, in people with heart disease, the hazard ratio for major cardiovascular events was 1.12 (95% CI 0.64–1.96). Lilly said there were fewer events than expected, so the estimate is imprecise.[10] A 10,000-person cardiovascular and kidney outcomes trial is expected to complete its main phase in 2029.[13]
- Long-term side effects are unknown. The longest published treatment period is 104 weeks.[2]
All of this describes Lilly's drug given under supervision. Nothing in it applies to products of unknown origin.
Unapproved products carry extra riskTrial participants received drug made by Lilly. Products sold online as "research use only" are not the same thing and have not been checked for identity, dose or sterility. A 2026 study in JAMA Network Open collected adverse events reported by people using nonapproved retatrutide.[19] See what the FDA says about these products.
Related
- Results by doseWeight loss in each trial
- Dosage chartHow doses were escalated
- Retatrutide vs tirzepatideHow the trial data compare
- Skin sensitivityDysesthesia rates in every trial
- Heart rate and blood pressurePulse, rhythm and heart outcomes
Frequently asked questions
What is the most common side effect of retatrutide?
Nausea. In TRIUMPH-1 it affected 42.4% of people on 12 mg and 14.8% on placebo.[1]
Does retatrutide cause muscle loss?
In the only published scan study, most weight lost was fat, and the lean share was similar to other obesity treatments. Muscle strength was not measured.[14]
What are the long-term side effects of retatrutide?
Is retatrutide safe for the heart?
Do side effects get better over time?
In the trials, stomach side effects were most frequent during dose escalation, and the phase 2 heart-rate increase peaked around week 24 and then declined.[6] The published papers give the detailed timing.
Sources
- Jastreboff AM et al. Retatrutide for obesity (TRIUMPH-1)
- Lilly: retatrutide delivered powerful weight loss in pivotal phase 3 obesity trial (TRIUMPH-1)
- Schnitzer TJ et al. Retatrutide in obesity and knee osteoarthritis (TRIUMPH-4)
- Schnitzer TJ et al. Retatrutide in obesity and knee osteoarthritis (TRIUMPH-4, TRIUMPH-1-OA), author accepted manuscript
- Lilly: retatrutide delivered weight loss of up to 71.2 lbs in TRIUMPH-4
- Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial
- Rosenstock J et al. Retatrutide in people with type 2 diabetes: a phase 2 trial
- Was dysesthesia reported as an adverse event in the retatrutide TRIUMPH trials?
- Bellido V et al. Retatrutide in obesity with type 2 diabetes (TRIUMPH-2)
- Lilly: retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3)
- Bajaj HS et al. Retatrutide in type 2 diabetes (TRANSCEND-T2D-1)
- Lilly: retatrutide vs semaglutide 2 mg in TRANSCEND-T2D-2
- Retatrutide studies (NCT04881760, NCT05929066, NCT05931367, NCT06662383, NCT07629401 and others)
- Coskun T et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2 randomised trial
- Zepbound (tirzepatide) prescribing information
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)
- Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1)
- A study of retatrutide (LY3437943) in participants who have obesity or overweight (TRIUMPH-1), NCT05929066, eligibility criteria
- Sehgal NKR et al. Self-reported adverse events with nonapproved retatrutide