Quick answer: the most common retatrutide side effects in phase 3 trials were nausea, diarrhea, constipation and vomiting, and they rose with dose. On the top 12 mg dose in TRIUMPH-1, 42.4% of people had nausea versus 14.8% on placebo, and 11.3% stopped treatment because of side effects.[1] The less familiar one is dysesthesia, an abnormal skin sensation reported in up to about 21% of people in one trial.[5]

Retatrutide is an investigational drug from Eli Lilly that is not approved by the FDA. Everything below comes from controlled trials. For background, see the retatrutide profile and the retatrutide dosage guide, which explains how the doses were reached.

Side effects by dose in TRIUMPH-1

TRIUMPH-1 enrolled 2,339 adults with obesity and no diabetes for 80 weeks, and the published paper confirms that the most common adverse events were gastrointestinal.[2] Lilly’s topline report gave the rates:[1]

Side effect4 mg9 mg12 mgPlacebo
Nausea28.6%38.4%42.4%14.8%
Diarrhea25.2%34.1%32.0%13.5%
Constipation23.8%25.9%26.1%10.9%
Vomiting10.6%22.8%25.3%4.8%
Dysesthesia5.1%12.3%12.5%0.9%
Urinary tract infection7.5%8.8%8.4%5.3%
Stopped due to side effects4.1%6.9%11.3%4.9%

Upper respiratory infections were also common (12.2% to 14.2%), but nearly as common on placebo (11.6%).[1]

Side effects in people with type 2 diabetes

TRIUMPH-2 tested the same three doses in 1,152 adults with obesity and type 2 diabetes. The published paper reports:[3]

  • Diarrhea: 27%, 34% and 34% on 4, 9 and 12 mg, versus 13% on placebo.
  • Nausea: 14%, 21% and 28%, versus 8%.
  • Low blood pressure (hypotension): 1%, 5% and 6%, versus under 1%.
  • Dysesthesia: 4%, 6% and 7%, versus 1%.
  • Stopping for side effects or death: 4% on 4 mg, 12% on 9 mg and 8% on 12 mg, versus 5% on placebo.

Seven people died during TRIUMPH-2 across all four groups, including one on placebo. Investigators judged none of the deaths related to the study drug.[3]

In TRANSCEND-T2D-1, a 40-week trial in 537 adults with early type 2 diabetes, stomach side effects were mostly mild to moderate and subsided over time. Between 2% and 5% of people on retatrutide stopped because of side effects, versus none on placebo, and no severe low blood sugar was reported.[6]

Dysesthesia: the skin-sensation side effect

Dysesthesia means an unpleasant or abnormal sensation, such as tingling, burning or skin that feels sensitive to touch.

How often it was reported, versus placebo:

TrialRetatrutidePlacebo
TRIUMPH-1 (obesity)5.1% to 12.5%0.9%
TRIUMPH-2 (obesity and diabetes)4.5% to 7.3%0.7%
TRIUMPH-3 (obesity and heart disease)6.4%1.3%
TRIUMPH-4 (obesity and knee arthritis)8.8% to 20.9%0.7%

Sources: TRIUMPH-1,[1] TRIUMPH-2 and TRIUMPH-3,[4] TRIUMPH-4.[5]

Lilly described the events as generally mild to moderate. It said most resolved while people kept taking retatrutide, and that dysesthesia rarely led anyone to stop.[1][5] The cause has not been explained in the published summaries.

Stopping treatment: why rates differed by trial

The share of people who stopped because of side effects varied a lot:

  • TRIUMPH-3 (severe obesity and heart disease): 9.8% on 9 mg and 13.5% on 12 mg, versus 4.8% on placebo.[4]
  • TRIUMPH-4 (knee osteoarthritis): 12.2% on 9 mg and 18.2% on 12 mg, versus 4.0% on placebo.[5]

Lilly said the TRIUMPH-4 rates were closely linked to starting body weight and included people who stopped because they felt they had lost too much weight. Among participants who started with a BMI of 35 or more, the rates were 8.8% and 12.1%, versus 4.8% on placebo.[5]

Heart rate, blood pressure and other effects

  • Heart rate: in the 48-week phase 2 trial, heart rate rose with dose, peaked at 24 weeks and then declined.[7]
  • Blood pressure: retatrutide generally lowered it. In TRIUMPH-3, the 12 mg dose lowered systolic blood pressure by 9.3 mmHg on average.[4] Even so, low blood pressure was reported as a side effect more often than with placebo in TRIUMPH-2.[3]
  • Decreased appetite: reported as a side effect in up to 19% of people in TRIUMPH-4 (versus 9.4% on placebo).[5]
  • Starting dose matters: in phase 2, starting at 2 mg rather than 4 mg partly reduced stomach side effects.[7] In phase 3, everyone started at 2 mg and stepped up every four weeks.[1]

Hair loss, fatigue, insomnia and anxiety

These come up often in searches, but the phase 3 summaries released so far do not list them among the most common side effects. The best data on them come from a different source.

A 2026 study in JAMA Network Open analyzed public posts by 13,589 people on a large social media site who said they were taking retatrutide, almost always from unapproved sources. Among the 7,823 who described at least one symptom, the most common were increased appetite (17.1%), fatigue (15.2%), increased energy (12.4%), nausea (11.6%), insomnia (6.1%) and a raised heart rate (4.8%). Anxiety was mentioned by 3.8% and hair loss by 0.6%.[8]

FDA says products sold as “research” retatrutide are of unknown quality, and that retatrutide cannot be used in compounding.[9] Side effects from such products may not match the trial results at all.

When to call a clinician

If you are in a trial, report side effects to the study team. In general, the warning signs that matter with this class of drug include:

  • vomiting or diarrhea that stops you keeping fluids down
  • severe or persistent stomach pain
  • dizziness or fainting, which can signal low blood pressure or dehydration
  • a racing or irregular heartbeat
  • skin pain or tingling that is getting worse

Questions to ask a clinician

  • Which approved medicines would suit me, and how do their side effects compare?
  • Am I eligible for a retatrutide clinical trial?
  • How should nausea be managed while a dose is being increased?
  • Should my heart rate or blood pressure be checked more often?

For how these effects compare with tirzepatide’s label, see retatrutide vs tirzepatide. For the wider drug class, see our guides to GLP-1 side effects and GLP-1 nausea, and the retatrutide vs semaglutide comparison.