Adverse effect · Retatrutide

How common is dysesthesia with Retatrutide?

B
Grade B — probable, not settled1 phase 3 RCT published; phase 3 topline · effect size: small · adverse
Short answerProbable, not settled. Human data exist (1 phase 3 RCT published; phase 3 topline) and mostly agree, showing a small effect — but too few, too small, or not yet peer-reviewed for a firm answer. TRIUMPH-2, published: dysesthesia in 4%, 6% and 7% on 4, 9 and 12 mg versus 1% on placebo; hypotension was also more frequent (1%, 5% and 6% vs under 1%). Press releases: 9–21% of treated participants vs 0.7% on placebo in TRIUMPH-4, and 4.5–7.3% vs 0.7–1.3% in TRIUMPH-2 and -3 — an effect not prominent with older GLP-1 drugs.

What the studies show

TRIUMPH-2, published: dysesthesia in 4%, 6% and 7% on 4, 9 and 12 mg versus 1% on placebo; hypotension was also more frequent (1%, 5% and 6% vs under 1%). Press releases: 9–21% of treated participants vs 0.7% on placebo in TRIUMPH-4, and 4.5–7.3% vs 0.7–1.3% in TRIUMPH-2 and -3 — an effect not prominent with older GLP-1 drugs.

“Hypotension and dysesthesia were more frequent with retatrutide than with placebo (four [1%] in the 4 mg group, 14 [5%] in the 9 mg group, and 18 (6%) in the 12 mg group vs one [<1%] in the placebo group with hypotension; 13 [4%], 16 [6%], and 21 [7%] vs two [1%] in the placebo group with dysesthesia).”

Verbatim, from the abstractBellido 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)

Human trials exist and mostly agree, but there are too few of them, they are too small, or one big one is still reading out. Expect the grade to move.

  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
  3. 3
    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 Topline; not peer-reviewed.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 dysesthesia?
Not yet settled. 1 phase 3 RCT published; phase 3 topline — LYO grades it B, meaning probable but liable to change as trials read out.
What studies are behind the grade?
TRIUMPH-2, published: dysesthesia in 4%, 6% and 7% on 4, 9 and 12 mg versus 1% on placebo; hypotension was also more frequent (1%, 5% and 6% vs under 1%). Press releases: 9–21% of treated participants vs 0.7% on placebo in TRIUMPH-4, and 4.5–7.3% vs 0.7–1.3% in TRIUMPH-2 and -3 — an effect not prominent with older GLP-1 drugs.
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 →