Retatrutide Side Effects: What the Clinical Trials Actually Reported

These are the most common events and the main reason people stopped treatment early. In Phase 2, gastrointestinal events were dose-related, mostly mild to moderate, and partly reduced by starting at 2 mg instead of 4 mg. In Phase 3, every participant started at 2 mg and stepped up every 4 weeks.

TRIUMPH-1 (80 weeks, no diabetes), from Lilly’s release:

At 12 mg, secondary reports add vomiting at 25.3% and constipation at 26.1%. Urinary tract infections were reported by 7.5% to 8.8% of retatrutide participants versus 5.3% on placebo.

Rates differ between trials. Nausea at 12 mg was 42.4% in TRIUMPH-1, 28.0% in TRIUMPH-2 (type 2 diabetes) and 22.4% in TRIUMPH-3 (cardiovascular disease). The releases do not explain the spread.

Dysaesthesia means an abnormal sensation of the skin, such as tingling or burning. It was not a headline finding in earlier incretin trials, and a Pharmacy Times commentary calls it novel for this drug class. It showed up in every Phase 3 trial, and it was highest in TRIUMPH-4:

In TRIUMPH-4, 9 mg gave dysaesthesia in 8.8% and discontinuation in 12.2%. Lilly describes the events as generally mild to moderate, mostly resolving during treatment, and rarely causing discontinuation.

What has not been published in the releases reviewed: which parts of the body are affected, how severe the worst cases were, whether it resolves after stopping, and what causes it. For scale, one report puts dysaesthesia with Lilly’s oral drug orforglipron at 1.2% at its highest dose.

• Dose. In TRIUMPH-1, the 4 mg arm (one escalation step) stopped for adverse events less often than placebo, 4.1% versus 4.9%. The 12 mg arm stopped at 11.3%.
• Baseline BMI. In TRIUMPH-4, participants with a baseline BMI of 35 or more discontinued at 8.8% (9 mg) and 12.1% (12 mg), well below the whole-trial 12.2% and 18.2%. Lower-BMI participants therefore stopped more often (PharmExec).
• Escalation. Gastrointestinal events cluster during dose escalation, which is why Phase 3 used a slow 4-week step schedule.

Phase 2 reported dose-dependent increases in heart rate that peaked at 24 weeks and declined thereafter. In the Phase 2 diabetes trial, pulse rose by up to 3.9 beats per minute at 36 weeks, versus a fall of 3.2 on placebo and a rise of 1.8 with dulaglutide. Heart-rate data were not in the Phase 3 releases reviewed.

Because the glucagon receptor raises glucose, hyperglycaemia was a design concern. In TRIUMPH-3, it was reported by 3.9% (9 mg) and 3.1% (12 mg) of retatrutide participants versus 13.4% on placebo. The Phase 2 diabetes trial reported no severe hypoglycaemia.

TRIUMPH-3 tracked heart attack, stroke and cardiovascular death but was not powered to test them. The five-component measure gave a hazard ratio of 0.82 (95% CI 0.55 to 1.22). The three-component measure gave 1.12 (95% CI 0.64 to 1.96). Both intervals include no effect, and the second has a point estimate above 1, which is why analysts are watching the dedicated outcomes trial (Reuters via Benefits and Pensions Monitor).

Large weight loss from any method removes some lean tissue. The only published retatrutide DXA data come from a Phase 2 substudy in 189 people with type 2 diabetes (Lancet Diabetes & Endocrinology, 2025):

• Total fat mass at 36 weeks fell 26.1% (8 mg) and 23.2% (12 mg), versus 4.5% on placebo and 2.6% on dulaglutide.
• Secondary summaries put lean tissue at roughly 35% of combined fat-plus-lean loss in the pooled retatrutide groups. The study did not measure skeletal muscle separately or test strength (RX Index).
• The authors concluded the weight loss did not come at the cost of disproportionate lean-mass loss.

Phase 3 body-composition and bone-density data had not been reported in the releases reviewed.

• Safety beyond about two years of treatment (the TRIUMPH-1 extension is the longest).
• Rare events, which usually emerge only after wide use.
• Whether dysaesthesia has a lasting course in the people who stop.
• Any regulator-reviewed risk list. Approved incretin drugs carry warnings (gallbladder disease and pancreatitis among them), but retatrutide has no label, so those are class expectations, not retatrutide findings.

Trial participants were screened, titrated and monitored by clinicians. These rates describe that setting only.

Nordapep supplies retatrutide for laboratory research use only. It is not a medicine and is not for human or veterinary use.