Adverse effect · Retatrutide

How common is GI side effects with Retatrutide?

A
Grade A — established in humans2 phase 3 + 1 phase 2 RCT published; phase 3 topline · effect size: large · adverse
Short answerEstablished in humans. 2 phase 3 + 1 phase 2 RCT published; phase 3 topline point the same way: a large effect. TRIUMPH-2, published: diarrhoea in 27–34% vs 13% on placebo and nausea in 14–28% vs 8%; 12% on 9 mg and 8% on 12 mg stopped treatment because of adverse events or death, against 5% on placebo. TRIUMPH-1, published, also names gastrointestinal events as the most common. Press releases: TRIUMPH-4, nausea 38–43% vs 11%, vomiting 20–21% vs 0%, discontinuation for adverse events 12–18% vs 4%; TRIUMPH-1, 11.3% stopped on 12 mg vs 4.9% placebo; TRIUMPH-3, 13.5% vs 4.8%.

What the studies show

TRIUMPH-2, published: diarrhoea in 27–34% vs 13% on placebo and nausea in 14–28% vs 8%; 12% on 9 mg and 8% on 12 mg stopped treatment because of adverse events or death, against 5% on placebo. TRIUMPH-1, published, also names gastrointestinal events as the most common. Press releases: TRIUMPH-4, nausea 38–43% vs 11%, vomiting 20–21% vs 0%, discontinuation for adverse events 12–18% vs 4%; TRIUMPH-1, 11.3% stopped on 12 mg vs 4.9% placebo; TRIUMPH-3, 13.5% vs 4.8%.

“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 vs. 4 mg).”

Verbatim, from the abstractJastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med, 2023;389:514–526

Several well-run randomised trials in people, pointing the same way. You can plan around this. It still says nothing about whether the effect is worth the side effects for you.

  1. 1
    Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.Lancet, 2026 (online 29 Sep)1,152 randomised, 92 sites, 80 weeks; −18.8% on 12 mg vs −5.1% placebo (treatment-regimen estimand). NCT05929079.
  2. 2
    Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).N Engl J Med, 2026 (online 29 Sep)2,339 randomised, 80 weeks; −25.0% on 12 mg vs −3.9% placebo by intention to treat. Subgroups with knee osteoarthritis (n=574) and obstructive sleep apnoea (n=243). NCT05929066.
  3. 3
    Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.N Engl J Med, 2023;389:514–526338 adults; −24.2% at 48 weeks on 12 mg.
  4. 4
  5. 5
    Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).Press release, May 20262,339 adults, 80 weeks plus 104-week extension. Detailed data promised for the ADA Scientific Sessions; not peer-reviewed at time of review.
  6. 6
    Eli Lilly. Lilly's triple agonist retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3).Press release, 23 Jul 2026TRIUMPH-2: 1,152 adults with obesity and type 2 diabetes, 80 weeks. TRIUMPH-3: 1,949 adults with severe obesity and cardiovascular disease, 80 weeks. Topline; not peer-reviewed. Lilly intends to file with the FDA in Q1 2027.

In context

Retatrutide is an investigational once-weekly peptide that activates three receptors at once: GIP, GLP-1 and glucagon. In TRIUMPH-1, a 2,339-person phase 3 trial published in September 2026, adults with obesity lost 25.0% of body weight at 80 weeks on the top dose against 3.9% on placebo; in adults who also have type 2 diabetes the figure was 18.8% (TRIUMPH-2). A separate published trial cut HbA1c by up to 1.9 percentage points. It is not approved anywhere, and no legitimate supply exists outside clinical trials.

Retatrutide is investigational. Legal status differs by country — see the regulation section or the jurisdiction pages.

Questions

Is Retatrutide proven to cause GI side effects?
Yes, as far as human trials can show it: 2 phase 3 + 1 phase 2 RCT published; phase 3 topline. LYO grades this outcome A.
What studies are behind the grade?
TRIUMPH-2, published: diarrhoea in 27–34% vs 13% on placebo and nausea in 14–28% vs 8%; 12% on 9 mg and 8% on 12 mg stopped treatment because of adverse events or death, against 5% on placebo. TRIUMPH-1, published, also names gastrointestinal events as the most common. Press releases: TRIUMPH-4, nausea 38–43% vs 11%, vomiting 20–21% vs 0%, discontinuation for adverse events 12–18% vs 4%; TRIUMPH-1, 11.3% stopped on 12 mg vs 4.9% placebo; TRIUMPH-3, 13.5% vs 4.8%.
Is Retatrutide approved for this?
No. Retatrutide is investigational; it is not an approved medicine for any indication in the jurisdictions LYO covers.

Other outcomes for Retatrutide

Written and maintained by LYO Research — how pages are written and checked. Reviewed 7 October 2026. Grades count human evidence only; see how LYO grades. Not medical advice. Correct this page →