Retatrutide Side Effects: What Clinical Trials Found

Retatrutide has no approved label yet

Retatrutide is an investigational drug from Eli Lilly. Investigational means it is still being tested in clinical trials and is not approved for any use. The FDA says retatrutide has not been found safe and effective for any condition and can’t be used in compounding under federal law.

Approved drugs have a label listing side effects; retatrutide doesn’t. This page draws on trial papers, ClinicalTrials.gov records and Lilly press releases. Outside experts have not checked the press releases, so they are labeled below.

In trials, an adverse event is any health problem that happens during the study, whether or not the drug caused it. That is why trials compare against placebo, a dummy injection with no drug in it.

What are the most common side effects of retatrutide?

TRIUMPH-1 was an 80-week phase 3 trial of 2,339 adults with obesity or overweight and no diabetes. Gut side effects were generally more common at higher doses. Lilly reported these figures in a press release before the NEJM paper came out on September 29, 2026.

In TRANSCEND-T2D-1, a 40-week phase 3 trial in adults with type 2 diabetes, Lilly said gut side effects happened mainly during dose escalation. Dose escalation is the period when the dose is raised step by step. The published paper says these events were generally mild to moderate and eased over time.

Did the starting dose matter?

The phase 2 trials tested this. Some groups started at 2 mg and others at 4 mg before reaching the same final dose. In the obesity trial, the authors reported that the lower 2 mg start partly reduced gut side effects. Posted results on ClinicalTrials.gov show the gap. For a final dose of 8 mg, nausea was reported by 17% of people who started at 2 mg and 60% of those who started at 4 mg. For 4 mg, it was 18% versus 36%. Placebo was 11%. Each starting-dose group had 33 to 35 people.

The phase 2 diabetes trial showed the same pattern. Gut side effects ranged from 13% on 0.5 mg to 50% in the 8 mg group that started at 4 mg, compared with 13% on placebo. The phase 3 trials below all started everyone at 2 mg. This describes how the trials were run. It is not a dosing schedule.

Doses studied in the trials

These are research doses only. There is no approved retatrutide dose or schedule. For the math behind each trial dose, see the retatrutide trial dose calculator.

The phase 2 diabetes trial also compared against dulaglutide 1.5 mg, an approved GLP-1 drug. In phase 3, Lilly said the dose went up every four weeks until people reached their assigned dose. For weight results, see TRIUMPH-1 results.

Side effects across the phase 3 trials

Each row below is a separate trial with different people, lengths and health conditions. Compare 12 mg with placebo within a row; comparing rows can mislead.

12 mg vs placebo. “Press release” means the numbers shown come from Lilly; TRANSCEND-T2D-1 and TRIUMPH-1 have since been published in journals. *TRIUMPH-2 counts stopping because of side effects or death.

How many people stopped retatrutide because of side effects?

Discontinuation means stopping the study drug for good. In TRIUMPH-1, 4.1% of people on 4 mg stopped because of side effects, compared with 4.9% on placebo. On 12 mg it was 11.3%.

TRIUMPH-4 had the highest rate: 18.2% on 12 mg. Lilly said in a press release that these rates were linked to starting BMI. Some people stopped because they felt they were losing too much weight. Among people with a BMI of 35 or higher, the rate on 12 mg was 12.1%.

Retatrutide skin sensitivity and tingling (dysesthesia)

Dysesthesia is an abnormal skin feeling, such as tingling or sensitivity to touch. It is uncommon with tirzepatide: the Zepbound label, from separate trials, lists it in 0.2% to 0.4% of people.

In TRIUMPH-1, it was reported by 5.1%, 12.3% and 12.5% of people on 4, 9 and 12 mg, compared with 0.9% on placebo. Lilly said these events were generally mild to moderate, most went away during treatment, and most people kept taking the drug. In TRIUMPH-4, Lilly said they rarely led people to stop.

The phase 2 obesity trial’s posted results list allodynia, pain from a touch that would not normally hurt, in 4 of 62 people on 12 mg and none on placebo.

Does retatrutide raise heart rate?

Yes, in the phase 2 obesity trial. Heart rate rose more at higher doses, peaked at 24 weeks and then declined. The abstract does not give the size of the rise.

The Zepbound label lists an average rise of 1 to 3 beats per minute, from different trials of a different drug.

Other side effects the trials reported

• Low blood pressure (hypotension): In TRIUMPH-2, it was reported by 1%, 5% and 6% of people on 4, 9 and 12 mg, compared with less than 1% on placebo.
• Urinary tract infections: 7.5% to 8.8% on retatrutide versus 5.3% on placebo in TRIUMPH-1, per Lilly.
• Low blood sugar: The phase 2 diabetes trial and TRANSCEND-T2D-1 reported no severe hypoglycemia.
• Pancreas, gallbladder and heart rhythm: Across the two phase 2 trials, the posted results list three serious cases of acute pancreatitis (inflammation of the pancreas), two of gallbladder inflammation and one of atrial fibrillation, an irregular heartbeat. A handful of cases can’t show whether the drug caused them.

What is still unknown

• Long-term heart and kidney safety: TRIUMPH-OUTCOMES is following about 10,000 people. ClinicalTrials.gov lists its estimated completion as February 2029.
• Full phase 3 safety tables: for most phase 3 trials, the detailed numbers here come from press releases. TRIUMPH-3 and TRIUMPH-4 have not been published in journals yet.
• Rare side effects: trials of a few thousand people can miss problems that show up only after a drug is widely used.