Retatrutide Side Effects: The Short Version

The most common side effects reported in retatrutide's Phase 3 trials were gastrointestinal: nausea, diarrhea, constipation and vomiting. In announcing TRIUMPH-1, TRIUMPH-4 and TRANSCEND-T2D-1, Lilly said the types of adverse events were generally consistent with trials of other incretin-based therapies, the class that includes semaglutide and tirzepatide. In TRIUMPH-1, the pivotal obesity trial, published in full in September 2026, 11.2% of participants on the highest dose stopped treatment because of adverse events, against 4.6% on placebo. The published paper also shows that low blood pressure was more common on retatrutide.

One side effect has drawn more attention than the rest: dysesthesia, an altered sense of touch often described as skin sensitivity. It was reported far more often than with tirzepatide, but it is not unique to retatrutide — semaglutide's US label lists it too, at 22% on its highest dose.

Trials count every adverse event that occurs during treatment, whether or not the drug caused it, which is why placebo groups report them too. The TRIUMPH-1 figures below come from the paper published in the New England Journal of Medicine; the others come from Lilly's announcements, although TRIUMPH-2 and TRANSCEND-T2D-1, a trial in type 2 diabetes, have also been published in full in The Lancet.

Retatrutide Side Effects by Dose

TRIUMPH-1 enrolled 2,339 adults with obesity or overweight and without diabetes, and compared three doses with placebo over 80 weeks.

Nausea, vomiting, dizziness and the share who stopped because of adverse events rose steadily with the dose. Not everything did: diarrhea and fatigue were slightly less common on 12 mg than on 9 mg, abdominal pain was least common on 9 mg, and upper respiratory tract infections, which occurred at close to the placebo rate, were most frequent on 4 mg. At 12 mg, nausea, diarrhea, constipation and vomiting were roughly 2.4 to 5.3 times as common as on placebo, and dysesthesia more than ten times. All figures come from the published paper except the per-dose urinary tract infection rates, which come from Lilly's announcement; the paper gives only a range, 7.5% to 8.7% across the three doses against 5.3% on placebo, and says 92% of these infections occurred in women and none led to stopping treatment. Apart from urinary tract infections, the main text of the paper does not report side effects separately for women and men.

Side Effects Across the Five Reported Phase 3 Trials

Results have been announced from five Phase 3 trials. The table shows the main adverse events reported for the 12 mg dose in each, with the placebo rate in parentheses; "Not listed" means the source for that trial gave no figure for that event. The TRIUMPH-1 column comes from the published paper, except urinary tract infections, and the other columns from Lilly's announcements. TRIUMPH-3's announcement also listed hyperglycemia, which was more common on placebo (13.4%) than on 12 mg (3.1%).

Nausea rose with the dose in all five trials, though only slightly in TRIUMPH-3 (21.7% on 9 mg, 22.4% on 12 mg). Diarrhea did not follow the dose as closely: it was lower on 12 mg than on 9 mg in four of the five. Rates also differed from trial to trial — nausea at 12 mg ranged from 22.4% in TRIUMPH-3 to 43.2% in TRIUMPH-4. The trials enrolled different populations and ran for different lengths of time, so the columns are not directly comparable.

How Many People Stopped Because of Side Effects

The share who stopped generally rose with the dose, with one exception: in TRIUMPH-2, more people stopped on 9 mg than on 12 mg. Population matters too. In TRIUMPH-4, a trial in people with knee osteoarthritis, the company said the rates were highly correlated with baseline BMI and included people who stopped because of perceived excessive weight loss; among participants with a BMI of 35 or more, the 12 mg figure was 12.1% rather than 18.2%. Trial length also differs: TRANSCEND-T2D-1 ran for 40 weeks, the others for 68 to 80.

The TRIUMPH-1 row shows the published paper's figures; the May 2026 announcement had given 4.1%, 6.9% and 11.3%, against 4.9% on placebo. The paper also reports that 0.3%, 1.0% and 5.3% of participants on 4 mg, 9 mg and 12 mg, and none on placebo, stopped because they or the site investigator considered their weight loss excessive or sufficient.

When Retatrutide Side Effects Start and How Long They Last

The TRIUMPH-1 paper describes the gastrointestinal events as mostly transient and mild or moderate, occurring most commonly during dose escalation, but neither the paper nor Lilly's announcements say how long individual episodes lasted. For TRANSCEND-T2D-1, the company said the most common adverse events — nausea, diarrhea and vomiting — occurred primarily during dose escalation, and in coverage of the trial's presentation at the American Diabetes Association meeting in June 2026 they were described as generally mild to moderate and easing over time.

The 48-week Phase 2 trial, published in full in 2023, gives the same picture in more detail: gastrointestinal adverse events occurred primarily during dose escalation, were mostly mild to moderate and were more frequent at higher doses, and the authors described them as transient.

For TRIUMPH-1, TRIUMPH-2, TRIUMPH-3 and TRANSCEND-T2D-1, the company reported that dysesthesia and urinary tract infections were generally mild to moderate and that the majority resolved during treatment. For TRIUMPH-4, it said the dysesthesia events were generally mild and rarely led to discontinuation. What happened to these events after people stopped treatment is not reported separately in the announcements or in the TRIUMPH-1 paper; what is known about stopping is covered in weight regain after stopping retatrutide.

Dysesthesia: What Is Known So Far

Dysesthesia is an altered sense of touch: tingling, burning, or ordinary contact feeling unpleasant or painful. It was reported more often on retatrutide than on placebo in all five Phase 3 trials with results so far. At 12 mg the rate ranged from 4.4% in TRANSCEND-T2D-1 to 20.9% in TRIUMPH-4; in TRIUMPH-1 it was 12.5%, against 0.9% on placebo. It rose with the dose in TRIUMPH-2 and TRIUMPH-4, and in TRIUMPH-1 from 4 mg to 9 mg, but not in TRIUMPH-3, where both doses had 6.4%, or in TRANSCEND-T2D-1. The published TRIUMPH-1 paper labels the category "dysesthesia: skin burning sensation and related adverse events" and describes it, together with injection-site reactions and low blood pressure, as mostly mild or moderate and nonserious; it does not say how long it lasted or what caused it.

Related events had appeared before. The Phase 2 trial reported cutaneous hyperesthesia and skin sensitivity in 7% of participants on retatrutide overall — 13% on the 12 mg dose — and 1% on placebo; none were severe, and none led to discontinuation.

Dysesthesia is not unique to retatrutide. Semaglutide's US label, revised in June 2026, lists it for both the 2.4 mg and 7.2 mg injections: 2% of patients against 1% on placebo in the three trials pooled for the 2.4 mg dose, and 22% on 7.2 mg and 6% on 2.4 mg, against 0.3% on placebo, in the later trials that tested the higher dose. The label says the incidence increases with dose. Tirzepatide's US label reports dysesthesia in 0.4% of patients on 15 mg, against 0.1% on placebo.

On these figures, retatrutide 12 mg in TRIUMPH-1 had a higher rate than semaglutide 2.4 mg on either measure and a far higher rate than tirzepatide, but a lower rate than semaglutide 7.2 mg. These are comparisons across different trials, and the sources may not count the same things: semaglutide's figures include related sensations such as paresthesia, burning and sensitive skin, while the TRIUMPH-1 paper describes its category only as skin burning sensation and related events, and neither the tirzepatide label nor Lilly's other announcements say which terms their figures include.

How Retatrutide Side Effects Compare With Semaglutide and Tirzepatide

The gastrointestinal and discontinuation figures come from each drug's pivotal obesity trial; the dysesthesia figures for tirzepatide and semaglutide come from their US labels, as described above — for tirzepatide, pooled from SURMOUNT-1 and SURMOUNT-2. The trials differed in length and population, so these are comparisons across separate trials, not head-to-head results. Weight loss on the same basis is compared in retatrutide vs tirzepatide vs semaglutide.

On those terms, tirzepatide had the lowest rate of every gastrointestinal event, though its placebo group also had the lowest rates. Retatrutide 12 mg and semaglutide 2.4 mg were within three percentage points of each other on all four. More people stopped retatrutide because of adverse events — 11.2%, against 7.0% for semaglutide and 6.2% for tirzepatide, with placebo rates of 4.6%, 3.1% and 2.6%.

Low Blood Pressure, Heart Effects and Rarer Side Effects

The company's announcements concentrate on the most common adverse events. The published TRIUMPH-1 paper also reports less common ones, including some, such as gallbladder problems and pancreatitis, that carry warnings on the labels of approved drugs in this class:

Low blood pressure stands out. It became more common as the dose rose, and the investigators wrote that it was more common in participants who were also taking blood pressure medicines; they described it, together with dysesthesia and injection-site reactions, the most frequent adverse events of special interest that were more common on retatrutide, as mostly mild or moderate and nonserious. Dizziness was reported in 12.0% of participants on 12 mg against 3.1% on placebo. Pulse rate rose on retatrutide, peaking at 20 weeks on 9 mg and 12 mg and decreasing after that; the data are covered in why retatrutide increases heart rate.

For pancreatitis, the investigators wrote that the small numbers do not permit conclusions about a treatment effect. The three severe or serious liver disorders, all on 12 mg, were a case of acute cholestatic hepatitis A, acute ischemic hepatitis most likely due to dehydration associated with Clostridium difficile colitis, and raised liver enzymes associated with worsening gallstone disease. Four participants on retatrutide and two on placebo died. One death, on 12 mg, was adjudicated as cardiovascular; it occurred in a participant with known heart failure 189 days after stopping retatrutide. The others were a motor vehicle accident and two sudden deaths, one noncardiovascular and one of undetermined cause, on 9 mg, and a motor vehicle accident and a gunshot wound on placebo. The investigators noted that the trial was not powered to assess cardiovascular safety. A trial of this size also cannot show how often rare events occur.

Cardiovascular events were counted more closely in TRIUMPH-3, which enrolled 1,949 people with a BMI of 35 or more and established cardiovascular disease. There were 27 major cardiovascular events — cardiovascular death, heart attack or stroke — among participants randomized to retatrutide (9 mg and 12 mg combined) and 23 among those randomized to placebo, a hazard ratio of 1.12 (95% confidence interval 0.64 to 1.96). On a broader measure that also counts death from any cause, heart failure events and coronary revascularization, there were 44 and 52, a hazard ratio of 0.82 (0.55 to 1.22). The company said such events occurred less often than anticipated in both groups. Twice as many participants were assigned to placebo as to each dose, so the combined retatrutide group and the placebo group were about the same size.

These pre-specified figures count all events during the study, whether or not participants were still taking their treatment. A further analysis that the company notes was not pre-specified, leaving out events more than 35 days after treatment stopped, gave hazard ratios of 0.92 (0.51 to 1.65) for the narrower measure and 0.73 (0.47 to 1.12) for the broader one. With this few events, every one of these confidence intervals includes no difference, so the results cannot show whether retatrutide raises or lowers cardiovascular risk. A separate trial with an enrollment goal of 10,000 people, TRIUMPH-Outcomes, is designed to determine whether retatrutide lowers serious heart-related complications or prevents worsening kidney function; the trial listing runs to February 2029.

The 48-week Phase 2 trial, with 338 adults, adds some detail. Heart rate rose with the dose, peaking at 24 weeks and declining after that. Cardiac arrhythmias — a category covering supraventricular arrhythmias and conduction disorders — were reported in 11% of participants on 12 mg and 3% on placebo; all were mild to moderate except one severe case of QT prolongation in a participant treated with ondansetron. Serious adverse events occurred in 4% of both the retatrutide and placebo groups. One participant on 12 mg had acute pancreatitis, and three on retatrutide had gallbladder events. A trial of this size cannot show how often rarer events occur.

In TRANSCEND-T2D-1, according to coverage of its presentation, no severe hypoglycemia was reported, and the two deaths during the study, both in the 4 mg group, were deemed unrelated to the study drug.

Why This Page Has No Management Advice

Many articles about retatrutide side effects include week-by-week dosing schedules, injection tips and advice on which medicines to take for nausea. This one does not, deliberately. Retatrutide has no approved dose or label, so there is no approved way to use it, and in the trials side effects were handled by the investigators running them.

Products sold online under the retatrutide name are not sold or supplied by Lilly, whose drug is available only through clinical trials and a limited expanded-access program. The company warns that such products "may contain unknown ingredients, harmful contaminants and impurities" — so the side effects reported in the trials say nothing reliable about what those products might do.

Retatrutide Side Effects in Summary

In Phase 3, the most common side effects of retatrutide were gastrointestinal, and nausea became more common at higher doses. At 12 mg in TRIUMPH-1, gastrointestinal rates were close to those of semaglutide 2.4 mg in its pivotal trial and above those of tirzepatide 15 mg, and more people stopped treatment because of adverse events than in either approved drug's pivotal trial — comparisons across separate trials, not head-to-head results. Dysesthesia was reported far more often than with tirzepatide, but semaglutide's label lists it too, at 2% to 6% on 2.4 mg and 22% on 7.2 mg.

The published TRIUMPH-1 paper adds detail the announcements did not, most notably low blood pressure, reported in 8.8% of participants on 12 mg against 0.9% on placebo. How long side effects last and how often rare events occur are still open questions (see retatrutide long-term safety) that longer follow-up and, if retatrutide is approved, an FDA label would address.

Sources

• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
• Eli Lilly. 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. December 11, 2025.
• Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. September 29, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes. March 19, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea, demonstrating its remarkable potential to treat obesity and its complications. June 6, 2026.
• Cleveland Clinic Journal of Medicine. Retatrutide yields substantial improvements in type 2 diabetes and obesity, phase 3 data from TRANSCEND-T2D-1 and TRIUMPH-1 show. ADA 2026 coverage, June 2026.
• 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(6):514–526.
• Eli Lilly. Lilly's SURMOUNT-1 results published in The New England Journal of Medicine show tirzepatide achieved between 16.0% and 22.5% weight loss in adults with obesity or overweight. June 4, 2022.
• Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002.
• Novo Nordisk. Wegovy (semaglutide) US prescribing information, section 6.1. Revised June 2026.
• Eli Lilly. US prescribing information for tirzepatide for weight reduction, section 6.1. Revised August 2026.
• Lilly Trials. The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults (TRIUMPH-Outcomes). NCT06383390, trial listing.
• Eli Lilly. What to know about retatrutide. Last updated September 2026.
• STAT. Eli Lilly to allow more patients to apply for special access to unapproved obesity drug. August 3, 2026.

Medical Disclaimer: This article is for informational purposes only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and products sold online under its name are not sold or supplied by Lilly. The side effects described here are those reported in clinical trials under medical supervision. Treatment decisions belong with a qualified healthcare provider.