Retatrutide side effects: what the trials reported

What it is

Retatrutide is an investigational weekly injection from Eli Lilly that switches on three hormone receptors: GLP-1, GIP and glucagon. In the trials it lowered body weight by up to a quarter on average, which is why its side effects are searched so often. This page gathers every adverse event the published trials reported, trial by trial, with the numbers. An adverse event is any unwanted medical occurrence during a trial, whether or not the drug caused it. That is why each figure is compared with the placebo group, people who received an injection with no active ingredient.

The trials themselves are summarised in Retatrutide: what the studies say.

What the studies looked at

• Phase 2, obesity: 338 adults, 48 weeks, weekly amounts of 1 mg to 12 mg (Jastreboff 2023).
• Phase 2, type 2 diabetes: 281 adults, 36 weeks, 0.5 mg to 12 mg (Rosenstock 2023).
• TRIUMPH-1: 2,339 adults with obesity and no diabetes, 80 weeks, 4 mg, 9 mg or 12 mg (Jastreboff 2026).
• TRIUMPH-2: 1,152 adults with obesity and type 2 diabetes, 80 weeks, 4 mg, 9 mg or 12 mg (Bellido 2026).
• TRIUMPH-4: 445 adults with obesity and knee osteoarthritis, 68 weeks, 9 mg or 12 mg. Only the company's announcement is public so far (Lilly, December 2025).

What the studies say

Digestive effects came first in every trial. Nausea, diarrhoea, constipation and vomiting were the most common adverse events. In phase 2 they rose with the dose, were mostly mild to moderate, and were partly reduced when the starting amount was 2 mg rather than 4 mg (Jastreboff 2023). In TRIUMPH-2 diarrhoea was reported by 27 %, 34 % and 34 % of the 4 mg, 9 mg and 12 mg groups against 13 % on placebo, and nausea by 14 %, 21 % and 28 % against 8 % (Bellido 2026).

Heart rate went up, then down. In phase 2 the resting heart rate rose with the dose, peaked at about 24 weeks and then declined while treatment continued (Jastreboff 2023).

Skin sensations. Dysesthesia, an abnormal skin sensation such as tingling, burning or sensitivity to touch, appeared in phase 3. In TRIUMPH-2 it was reported by 4 %, 6 % and 7 % of the retatrutide groups against 1 % on placebo (Bellido 2026). In TRIUMPH-4 the company reported 8.8 % with 9 mg and 20.9 % with 12 mg against 0.7 % (Lilly, December 2025).

Low blood pressure. In TRIUMPH-2 hypotension, meaning blood pressure below the normal range, occurred in 1 %, 5 % and 6 % of the retatrutide groups against under 1 % on placebo (Bellido 2026).

Stopping because of adverse events. In phase 2 obesity, 6 % to 16 % of the retatrutide groups stopped for this reason against none on placebo (Jastreboff 2023). In TRIUMPH-2, 4 %, 12 % and 8 % of the retatrutide groups stopped permanently because of adverse events or death, against 5 % on placebo (Bellido 2026). In TRIUMPH-4 the company reported 12.2 % and 18.2 % against 4.0 % (Lilly, December 2025).

Deaths. Seven participants died in TRIUMPH-2, six on retatrutide and one on placebo. The investigators judged none of the deaths related to the treatment (Bellido 2026).

How this compares with older weekly injections

The same family of side effects was reported with the approved weekly medicines semaglutide and tirzepatide, which act on one and two of the same receptors.

• Semaglutide 2.4 mg, STEP 1 trial, 68 weeks: nausea and diarrhoea were the most common adverse events, typically short-lived and mild to moderate, and 4.5 % stopped because of digestive events against 0.8 % on placebo (Wilding 2021).
• Tirzepatide, SURMOUNT-1 trial, 72 weeks: digestive events were the most common and mostly occurred while the dose was being increased. Between 4.3 % and 7.1 % of the tirzepatide groups stopped because of adverse events against 2.6 % on placebo (Jastreboff 2022).

The trials were run in different people, at different times and for different lengths, so these figures cannot be compared directly. Only a head-to-head trial can do that, and none has been published for retatrutide.

What the researchers flagged

• The longest published follow-up is 80 weeks. Effects over many years, and after stopping, are not yet known.
• TRIUMPH-3 and TRIUMPH-4 are known only from company announcements so far. Full papers give more detail, including rarer events.
• The heart and kidney outcomes trial, TRIUMPH-Outcomes, is not expected before 2029.
• All these findings come from medicines made by Lilly and given under supervision. They say nothing about the quality of research products.