Retatrutide Long-Term Side Effects: What the Longest Trials Show

Nobody knows what retatrutide does to the body over 5 or 10 years, because nobody has taken it that long. The longest published side effect data run 80 weeks, in four Phase 3 trials led by TRIUMPH-1, and the retatrutide long term side effects reported over that stretch were the familiar ones: nausea, diarrhea, constipation, vomiting and burning or sensitive skin. A 104-week extension exists, but Lilly has released only its weight results.

"Long term" means something shorter than most people assume: 80 weeks of side effect data and 2 years of weight data, as of October 2026. TRIUMPH-1 is now in the New England Journal of Medicine and TRIUMPH-2 in The Lancet, but neither gives a rate of serious side effects in its abstract.

Retatrutide long term side effects in the longest trials so far

Eight retatrutide trials of 36 weeks or longer have reported side effect results, and the 2-year extension has reported weight results only.

Stopping rates are for quitting treatment because of side effects, by dose. The TRIUMPH-1 percentages are from Lilly's release; the NEJM abstract says only that the most common adverse events were gastrointestinal. No Phase 3 paper or release gives a serious side effect rate, only the deaths above, and no Phase 3 trial has posted results on ClinicalTrials.gov yet.

In TRIUMPH-1, the biggest of them, Lilly said the types of side effects "were generally consistent with trials of other incretin-based therapies", the drug family that includes tirzepatide and semaglutide.

The 2-year numbers come from a filtered group. The TRIUMPH-1 extension took the first 532 people with a starting BMI of 35 or more who reached week 80 on their assigned injection without stopping or permanently lowering the dose. Some had been on placebo all along and got only 24 weeks of retatrutide. That's 532 of the 2,339 people randomized, fewer than 1 in 4 (our arithmetic).

Our read: the extension shows retatrutide kept working to 104 weeks in people who got on with it. It can't show whether side effects appear late, because anyone who had stopped or cut their dose by week 80 wasn't let in.

Do side effects fade or build up over time?

Mostly they fade. In TRANSCEND-T2D-1, nausea, diarrhea and vomiting came mainly while the dose was going up, and in the Phase 3 trials that happens every 4 weeks until the target dose. Our page on how long side effects last has the week-by-week timeline.

Heart rate runs on a slower clock: in the Phase 2 obesity trial it rose with dose, peaked at 24 weeks and then declined, per the NEJM paper (see the heart rate page).

Burning or oversensitive skin (dysesthesia) is harder to call. In TRIUMPH-1 it affected 12.5% of people on 12 mg against 0.9% on placebo, and Lilly said most cases resolved during treatment. That's "most", not all. On Wegovy 7.2 mg, 18% of people with dysesthesia hadn't recovered by the end of the trial, per the FDA label. That's semaglutide data, not retatrutide; the skin sensitivity page has the rest.

Some people stop because the drug works too well: Lilly said the 18.2% who quit on 12 mg in TRIUMPH-4 included people who felt they were losing too much weight.

How the 80-week side effects compare with Ozempic

TRANSCEND-T2D-2 is the first Phase 3 trial of retatrutide against another incretin drug. It was open-label: 1,298 adults with type 2 diabetes on metformin took retatrutide 9 mg, 12 mg or Ozempic 2 mg, the highest Ozempic dose. These are Lilly's release figures; the trial has no paper yet.

Stomach effects were close to Ozempic's, with diarrhea a few points higher on retatrutide and constipation lower. The gaps that stand out are skin sensitivity and stopping: 12 mg had about 3 times Ozempic's stopping rate (our arithmetic). Lilly released no serious side effect rate for this trial. Our Ozempic comparison covers the blood sugar and weight results from the same trial.

Heart, liver and blood sugar after a year or more

TRIUMPH-3 is the only retatrutide trial with results in people who already had heart disease: 1,949 adults with a BMI of 35 or more, followed for 80 weeks. Heart events came less often than expected in both groups, so the counts are thin.

• MACE-5 (a broad group of heart and stroke events): 44 on retatrutide (doses pooled) vs 52 on placebo, hazard ratio 0.82, with a 95% range of 0.55 to 1.22
• MACE-3 (heart attack, stroke or heart-related death): 27 on retatrutide (pooled) vs 23 on placebo, hazard ratio 1.12, with a range of 0.64 to 1.96

Both ranges cross 1, so TRIUMPH-3 can't show harm or benefit. Risk factors moved the right way on the highest dose: systolic blood pressure fell 9.3 mmHg, triglycerides 37.0% and hsCRP, a marker of inflammation, 51.2%. One thing to watch: the TRIUMPH-2 Lancet paper reported low blood pressure (hypotension) in 5% on 9 mg and 6% on 12 mg, against under 1% on placebo. Whether the risk-factor changes turn into fewer heart attacks is the job of TRIUMPH-Outcomes, with about 10,000 people. For scale, the semaglutide trial SELECT needed 17,604 people, treated for 34.2 months on average, to show 20% fewer events.

The liver data look reassuring so far. In the Phase 2 liver fat substudy (Nature Medicine, 2024), 98 people with fatty liver took retatrutide or placebo for 48 weeks; liver fat fell 86.0% on 12 mg and the authors reported no hepatotoxicity signals.

Severe low blood sugar hasn't shown up in the diabetes trials so far: the Phase 2 diabetes trial and TRANSCEND-T2D-1 both reported none. If you also take insulin or a sulfonylurea, the tirzepatide label advises considering lower doses of those drugs.

Gallbladder, pancreas, muscle and thyroid

These are the slow-burn risks, and retatrutide's own numbers are small. The Phase 2 obesity trial had 1 case each of acute pancreatitis (1 of 62 on 12 mg), acute gallbladder inflammation and acute kidney injury (both 1 of 35 on 8 mg). Groups this size can't give you a rate.

In the Zepbound trials (class evidence; more on our pancreatitis and gallbladder page), gallbladder inflammation (cholecystitis) hit 0.7% on tirzepatide against 0.2% on placebo, and pancreatitis 0.2% in both groups. The NIH lists fast weight loss as a gallstone risk, and people on 12 mg in TRIUMPH-1 lost an average of 28.3% over 80 weeks. The warning signs are in the box near the end of this page.

No Phase 3 body composition result has been published, so nobody can say yet how much of that lost weight is muscle; our muscle loss page covers what helps. We found no published retatrutide data on bone density either.

Zepbound, Mounjaro and Wegovy carry a boxed warning for thyroid C-cell tumors, based on findings that haven't been shown in people (see our cancer and thyroid page). Retatrutide has no label yet, so nobody knows whether it will carry the same warning.

Can you take reta forever?

Nobody has, so nobody can promise it's fine. The longest anyone has taken retatrutide in a published trial is 104 weeks. What the data do show is that stopping has a cost: in the Phase 2 liver substudy, people had already regained some weight at a safety visit 4 weeks after their last dose. Retatrutide's half-life is about 6 days, per the Phase 1b study in The Lancet (see half-life), so by then most of it has left the body.

The best guide to what happens after that is tirzepatide's withdrawal trial, SURMOUNT-4, published in JAMA in 2024. People took the highest tirzepatide dose they could tolerate for 36 weeks, and the 670 who finished that stretch had lost 20.9% on average. Half were then switched to placebo for a year.

People on placebo kept a bit under half of their 20.9% loss (our arithmetic). That's tirzepatide data, not retatrutide.

Tirzepatide also has 3-year data: in the SURMOUNT-1 follow-up in the NEJM, people with prediabetes took it for 176 weeks and the authors reported no new safety signals. Diabetes had been diagnosed in 1.3% of the tirzepatide group by 176 weeks, against 13.3% on placebo; 17 weeks after stopping, 2.4% and 13.7%.

Our read: if retatrutide behaves like tirzepatide, a finite course would give back about half the loss within a year of stopping, a better-measured long-term effect than any late side effect seen so far. The results page shows how much weight each dose took off, which is what's at stake if you stop.

The extra risk from products sold online

Everything above comes from Lilly's drug at measured doses under trial supervision. Lilly's FAQ, updated in October 2026, says retatrutide "is an investigational medicine that is not on the market" and that "no one can legally sell it for human use" (see is retatrutide legal). If you're weighing retatrutide for sale online as a long-term plan, the trial safety record doesn't transfer to it, and every extra month adds to your exposure to whatever is in the vial.

Victoria's Department of Health reported 6 cases of acute liver injury since January 2026 in people using unapproved products labeled Retatrutide, possibly linked to a contaminant. Australia's TGA tested a vial sold as retatrutide after a user was hospitalized with uncontrollable vomiting and a torn esophagus. It held no retatrutide, only undeclared semaglutide at about 8 times the level in approved products. Lilly's FAQ warns that illicit products may hold contaminants or the wrong ingredient entirely.

What long-term data are coming, and when

Dates are the estimates on ClinicalTrials.gov as of October 2026.

TRIUMPH-6 is the one to watch for the "forever" question: it's the first randomized retatrutide trial to test coming off it after 80 weeks.

On approval, Lilly last said, on September 29, 2026, that it plans to submit retatrutide to the FDA in the first quarter of 2027 as a Biologics License Application (BLA). On October 2, 2026, the FDA decided that retatrutide is a drug, not a biological product, so an application would need to be filed under section 505 of the Federal Food, Drug, and Cosmetic Act. Lilly's appeal on that question is pending in the Seventh Circuit, and we found no ruling as of October 31, 2026. Our FDA approval page tracks the filing.

If you're in a trial, tell the study team about every new symptom, even a year in; those reports become the long-term safety tables. For the full record, see is retatrutide safe.