Retatrutide

Like tirzepatide, retatrutide switches on the receptors for two gut hormones, GLP-1 and GIP, which act on insulin release, stomach emptying and appetite. It also switches on the glucagon receptor; glucagon raises energy use and affects how the liver handles fat and sugar, which is thought to add to the weight loss [2]. It is given as a weekly injection, with the dose raised in steps.

In a phase 2 trial, adults with obesity lost on average 24.2% of their body weight over 48 weeks on the 12 mg dose, against 2.1% with placebo [2]. In the phase 3 TRIUMPH-1 trial of 2,339 adults with obesity and without diabetes, average weight loss over 80 weeks was 23.7% on 9 mg and 25.0% on 12 mg, against 3.9% with placebo. The most common side effects were gastrointestinal [3]. Lilly reported further phase 3 trials in people with type 2 diabetes and in people with heart disease in 2026 [1].

The evidence comes from a 2026 study of almost 28,000 people taking semaglutide or tirzepatide [4]. It found two variants in the drugs' target receptors:

• GLP1R rs10305420 (Pro7Leu): each T allele was associated with about 0.76 kg more weight loss and with more nausea and vomiting, on both drugs. The semaglutide page explains it.
• GIPR rs1800437 (Glu354Gln): each C allele was associated with about 1.8 times the odds of moderate or severe vomiting, but only in people taking tirzepatide, the drug that acts on the GIP receptor. It did not affect weight loss. The tirzepatide page explains it.

Both receptors are retatrutide targets, so similar effects are plausible. They are not proven. Retatrutide acts on each receptor with its own strength, adds glucagon activity and is used at its own doses, and any of these could change how much each variant matters. Nobody taking retatrutide was in the study.

Gene2Rx does not assess the glucagon receptor gene, GCGR. No common GCGR variant has been shown to change the response to retatrutide.

The report reads GLP1R and GIPR together and applies the tirzepatide guidance to retatrutide. Every estimate on this page is borrowed from tirzepatide; none was measured in people taking retatrutide.

The advice follows the same pattern as for tirzepatide. With GIPR G/G, standard dosing and dose increases. With one or two GIPR C alleles, consider a slower dose-escalation schedule and expect more nausea or vomiting; a GLP-1-only medicine such as semaglutide is not affected by the GIPR variant. For the highest-risk combination, two GLP1R T alleles with two GIPR C alleles, the report suggests considering a GLP-1-only medicine, or starting at the lowest dose with a much slower schedule and close follow-up. If only one gene has a result, the report shows that gene's guidance alone.

People in retatrutide trials, and people who may be offered it after approval, are already asking whether the GLP1R and GIPR findings apply to them. The biology gives a reasonable answer: the variants sit in receptors retatrutide acts on, and the GIPR effect appeared only with a drug that acts on the GIP receptor [4]. The guideline gives that reasoning a consistent form, keeps standard dosing in every row and limits itself to the dose schedule, the tool already used to manage nausea.

This is the least certain guideline Gene2Rx publishes. It is a forward-looking extrapolation, and it will be replaced when genetic data from people taking retatrutide appear.

If you are in a retatrutide trial, follow the study team's instructions on dosing; tell them about your result if you think it is relevant, and report side effects as the study asks. Do not change how you take a study medicine on the basis of a genetic report.

Because retatrutide is not approved, any product sold outside a clinical trial under that name has not been reviewed by the FDA for quality or safety. The approved alternatives in the same family are semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), and their pages explain what the same variants mean for them.

Gene2Rx reads both positions from your DNA data, measured directly or inferred by imputation from nearby markers. Consumer arrays (23andMe, AncestryDNA, MyHeritage) are not clinical-grade tests, and their raw data is labeled not for medical use.

When will retatrutide be available?

Lilly has said it plans to submit retatrutide for U.S. approval in the first quarter of 2027 [1]. The FDA review takes months after that, and the outcome is not known in advance.

Will my GLP1R result mean more weight loss on retatrutide?

It might. The variant was associated with slightly more weight loss on both semaglutide and tirzepatide, about a kilogram per copy, but it has not been studied with retatrutide.

1. Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (July 23, 2026). TRIUMPH-2 and TRIUMPH-3 results and the plan to submit for U.S. approval in the first quarter of 2027.
2. Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med (2023). Weight loss at each dose over 48 weeks.
3. Jastreboff AM et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1). N Engl J Med (2026). The first phase 3 trial in obesity.
4. Su QJ, Ashenhurst JR, Xu W et al. Genetic predictors of GLP1 receptor agonist weight loss and side effects. Nature 653:770-775 (2026). The GLP1R and GIPR findings the guideline extrapolates.