Retatrutide side effects: every adverse event the trials have reported so far

By Retatrutide Risk editorial team. Published September 21, 2026. Sources at the end of the page.

Retatrutide is a single peptide that activates three receptors: GIP, GLP-1 and glucagon. Its side-effect profile therefore overlaps with the GLP-1 receptor agonists and with tirzepatide, but it is not identical, and the glucagon component brings questions of its own. This page lists what the registered clinical trials have actually reported, dose by dose, and flags what has not been measured yet.

Where the side-effect data come from

There are two published phase 2 trials and four phase 3 trials with topline announcements. The phase 2 trials are peer-reviewed and give the most detailed picture. The phase 3 results have so far been released only as company announcements, which report the most frequent adverse events and the discontinuation rates but not the full safety tables.

Gastrointestinal side effects: the dominant category

In the phase 2 obesity trial, the authors summarize the safety result in one sentence: the most common adverse events in the retatrutide groups were gastrointestinal, these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg versus 4 mg). The events named are nausea, diarrhea, vomiting and constipation.

The phase 2 type 2 diabetes trial gives frequencies. Mild-to-moderate gastrointestinal adverse events (nausea, diarrhea, vomiting, constipation) were reported by 67 of 190 participants on retatrutide (35%), ranging from 6 of 47 (13%) in the 0.5 mg group to 12 of 24 (50%) in the 8 mg fast-escalation group. On placebo the figure was 6 of 45 (13%), and on dulaglutide 1.5 mg it was 16 of 46 (35%). The 8 mg fast-escalation arm started at 4 mg; the 8 mg slow-escalation arm started at 2 mg. The difference between those two arms is the clearest evidence in the published record that the speed of escalation, not only the final dose, drives tolerability.

The phase 3 announcements report individual events by dose. The table below combines TRIUMPH-1 (obesity without diabetes) and TRIUMPH-2 (type 2 diabetes), both at 80 weeks.

In TRIUMPH-4, the company's medical information page gives ranges across the 9 mg and 12 mg arms: nausea 38.1% to 43.2%, diarrhea 33.1% to 34.7%, constipation 21.8% to 25.0% and vomiting 20.4% to 20.9%.

Two patterns are consistent across every trial. First, the gastrointestinal burden rises with dose. Second, the same dose produces lower rates in people with type 2 diabetes than in people without it, which was also seen with earlier incretin drugs.

How many people stop because of side effects

Discontinuation because of adverse events is the most useful single number for judging tolerability, because it captures events that were severe enough, or persistent enough, to make a participant leave a supervised trial.

At the lowest phase 3 dose, 4 mg, the dropout rate is not distinguishable from placebo. At 12 mg it is two to four times the placebo rate depending on the population. TRIUMPH-4, the smallest phase 3 trial, shows the highest figures.

In the phase 2 diabetes trial, 237 of 281 participants (84%) completed the study and 222 (79%) completed the study treatment, across all arms including placebo and dulaglutide.

Heart rate

The phase 2 obesity paper states that dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter. That is the extent of what the abstract reports; the full paper and its supplement carry the figures per arm. The phase 3 announcements do not mention heart rate. Because the phase 3 program includes a dedicated cardiovascular outcomes trial (TRIUMPH-Outcomes, NCT06383390, about 10,000 participants, event-driven, estimated primary completion February 2029), the definitive answer on whether this heart rate effect matters clinically will not exist for several years. The heart rate and arrhythmia article goes through this in more detail.

Dysesthesia: the signal that appeared in phase 3

Dysesthesia is an abnormal, often unpleasant sensation of the skin, such as tingling, burning or heightened sensitivity to touch. It was not highlighted in the phase 2 abstracts, but it appears in all three retatrutide phase 3 announcements that list it.

For comparison, the FDA prescribing information for tirzepatide (Zepbound) reports dysesthesia in 0.2% to 0.4% of treated patients versus 0.1% on placebo. The retatrutide rates are therefore an order of magnitude higher than for the closest approved drug. Lilly's medical information page describes the events in TRIUMPH-4 as generally mild and rarely leading to treatment discontinuation. The mechanism has not been explained in any published source.

Hypoglycemia

In the phase 2 type 2 diabetes trial there were no reports of severe hypoglycemia and no deaths. Participants in that trial were on diet and exercise alone or on metformin, not on insulin or sulfonylureas, which are the drugs that raise hypoglycemia risk when combined with any glucose-lowering incretin. The tirzepatide label, for the same reason, advises considering a lower dose of insulin or insulin secretagogues when starting treatment.

Other adverse events reported

TRIUMPH-1 lists urinary tract infections at 7.5% (4 mg), 8.8% (9 mg) and 8.4% (12 mg) versus 5.3% on placebo. The phase 1b multiple-ascending-dose trial reported treatment-emergent adverse events in 33 of 52 participants on LY3437943 (63%), 3 of 5 on dulaglutide (60%) and 8 of 15 on placebo (54%), with gastrointestinal disorders the most frequent category.

What the trials have not shown, or not yet

• Thyroid C-cell tumors. Approved GLP-1 receptor agonists and tirzepatide carry a boxed warning based on rodent studies, and are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2. No published retatrutide document addresses this yet; the question will be settled by the eventual FDA label, if the drug is approved.
• Pancreatitis, gallbladder disease and acute kidney injury from dehydration. These appear in the tirzepatide label as class warnings. The retatrutide announcements do not report them, which does not mean they did not occur; topline announcements list only the most frequent events.
• Long-term exposure. The longest reported exposure is the 104-week extension of TRIUMPH-1, in 532 participants. Nothing beyond that exists.
• Use outside trials. Every figure above comes from supervised participants with screening, exclusion criteria, dose escalation over months and regular monitoring.

Reading these numbers responsibly

Percentages from different trials are not directly comparable, because the populations, dose-escalation schedules and durations differ. The safest comparison is within a trial, against its own placebo arm. Read that way, the pattern is consistent: gastrointestinal events at rates two to three times placebo, a dose-related dropout rate that reaches double digits at 12 mg, a heart rate increase that peaks early, and a dysesthesia signal that is unusual for this class.

Also consider what the trial doses and escalation schedules actually were, and how the results compare with tirzepatide.