Retatrutide: research, uses and evidence

Retatrutide is an investigational triple agonist of the GIP, GLP-1 and glucagon receptors. In the phase 3 TRIUMPH-1 trial, adults with obesity lost an average of 28.3% of body weight at the 12 mg dose over 80 weeks, according to topline results Lilly reported in May 2026.

Structure

Single 39-residue peptide engineered to activate three receptors, with a fatty-acid side chain for once-weekly dosing.

How it works

Adding glucagon receptor activity to the incretin pair is intended to raise energy expenditure and increase fat oxidation in the liver, on top of the appetite reduction from GLP-1 and GIP signalling. In phase 2 MRI substudies, liver fat fell by more than 80% on average at the higher doses.

Research use cases

Areas where Retatrutide has been studied. Inclusion here does not mean it works for that purpose.

Obesity and overweight (phase 3)
Type 2 diabetes with obesity (phase 3)
Obesity with established cardiovascular disease (phase 3)
Knee osteoarthritis pain with obesity, MASLD and chronic kidney disease (studied)

What the research found

Phase 2 obesity trial

338 adults without diabetes were randomized to placebo or doses from 1 to 12 mg weekly. At 48 weeks, mean weight change at 12 mg was −24.2% versus −2.1% with placebo, and the weight curve had not yet levelled off.¹

Phase 2 type 2 diabetes trial

In 281 adults with type 2 diabetes, retatrutide lowered HbA1c by up to 2.02 percentage points and body weight by up to 16.9% at 36 weeks.²

Phase 3 TRIUMPH-1 (topline, 2026)

In 2,339 adults with obesity or overweight and no diabetes, Lilly reported mean weight loss of 19.0%, 25.9% and 28.3% at 4, 9 and 12 mg over 80 weeks. These results had been announced by the company but not yet published in a peer-reviewed journal at the time of our last review.³

Phase 3 TRIUMPH-2 and TRIUMPH-3 (topline, 2026)

In adults with type 2 diabetes, weight fell by up to 20.8% at 80 weeks. In adults with obesity and cardiovascular disease, weight fell by up to 22.6%. Exploratory cardiovascular event analyses were inconclusive.³

Safety and open questions

Gastrointestinal events were the most common adverse effects and increased with dose. In TRIUMPH-1, discontinuation for adverse events reached 11.3% at 12 mg versus 4.9% on placebo. Phase 2 trials showed a dose-dependent rise in resting heart rate that peaked around week 24. Some participants reported dysaesthesia (abnormal skin sensations). Long-term safety data are not yet available.

Regulatory status

Investigational (Eli Lilly). Phase 3 TRIUMPH programme reported 2026; Lilly has said it plans to file with the FDA in 2027. Not approved anywhere.

Status was accurate when this page was last reviewed on October 26, 2026. Regulations change; check with the relevant authority before relying on it.

Retatrutide: common questions

Is retatrutide approved?

No. As of October 2026 it is investigational. Lilly has reported positive phase 3 results and said it expects to submit to the FDA in early 2027. Products sold online as “retatrutide” are not the clinical-trial drug and are not subject to pharmaceutical quality control.

How does retatrutide differ from tirzepatide?

Tirzepatide activates two receptors (GIP and GLP-1). Retatrutide adds a third, the glucagon receptor, which is thought to raise energy expenditure and reduce liver fat. Direct head-to-head trial data are not yet available.

What is “GLP-3”?

It is an informal marketing nickname for retatrutide, not a scientific term. There is no hormone called GLP-3.

Is Retatrutide approved for human use?