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Research answer
How does retatrutide work?
Retatrutide is a single peptide that activates three hormone receptors at once: GIP, GLP-1 and glucagon, which its developer Eli Lilly calls a first-in-class triple agonist. As of 23 September 2026 it is investigational, studied in phase 3 trials for obesity, type 2 diabetes and knee osteoarthritis pain.
Primara Labs sells some of the compounds covered here. Every figure on this page links to its source and the date it was checked.
Updated 23 September 2026
01
The three receptors
Retatrutide is a single peptide that activates three receptors: GIP, GLP-1 and glucagon. Lilly describes it as a first-in-class triple hormone receptor agonist.
GLP-1 and GIP are incretins, gut hormones released after eating that act on insulin secretion and appetite signalling. Glucagon receptor activity is the part that sets retatrutide apart from dual agonists: glucagon acts on the liver and on energy expenditure. Tirzepatide acts on two of these receptors and semaglutide on one.
02
What the trials measured
The Research Desk rates retatrutide's evidence as phase 3 human. In TRIUMPH-1, a phase 3 trial in adults with obesity, or overweight with at least one weight-related condition, without diabetes (n=2,339), mean body weight fell 28.3% on the 12 mg arm over 80 weeks, against 2.2% lost on placebo (efficacy estimand).
In TRIUMPH-2, a phase 3 trial in adults with type 2 diabetes and obesity or overweight lasting 80 weeks, a1C fell 1.4, 1.6 and 1.5 points from a baseline of 7.7% on 4, 9 and 12 mg, against 0.2 on placebo.
03
Adverse events in the same trial
In TRIUMPH-1, discontinuation because of adverse events was 4.1% on 4 mg, 6.9% on 9 mg and 11.3% on 12 mg, against 4.9% on placebo. The most frequently reported adverse events were nausea in 28.6% on 4 mg, 38.4% on 9 mg and 42.4% on 12 mg against 14.8% on placebo, diarrhoea in 25.2% on 4 mg, 34.1% on 9 mg and 32.0% on 12 mg against 13.5% on placebo, constipation in 23.8% on 4 mg, 25.9% on 9 mg and 26.1% on 12 mg against 10.9% on placebo and vomiting in 10.6% on 4 mg, 22.8% on 9 mg and 25.3% on 12 mg against 4.8% on placebo.
Sources
Where every figure comes from
- Eli Lilly, retatrutide mechanism · checked 23 September 2026
- Eli Lilly topline release, 21 May 2026 · checked 23 September 2026
- Eli Lilly topline release, 23 July 2026 · checked 23 September 2026
Last reviewed 23 September 2026