Retatrutide and weight loss: what do the studies show?

There are two large randomized human studies published in scientific journals. Both measured weight as one of the outcomes, and both compared against placebo.

In the phase 2 study in obesity, participants were followed for 48 weeks. In the phase 3 study in type 2 diabetes, 537 adults were followed for 40 weeks. The figures below are group averages from clinical trials, not expected results for any individual person.

Gastrointestinal side effects were the most common in both studies, and they increased with dose. Neither study followed participants for longer than a year, so what happens over a longer time and after treatment ends is not addressed.

Retatrutide, also known as LY3437943, is a synthetic peptide. A peptide is a short chain of amino acids, the same building blocks that proteins are made of.

The substance activates three receptors: GLP-1, GIP and glucagon. Receptors are receiving structures on the surface of cells. GLP-1 and GIP are gut hormones that affect blood sugar and fullness. Glucagon affects how the body releases and uses energy.

The combination of all three is what is new. Earlier drugs in the same family act on one or two of the receptors.

The most cited study is a randomized phase 2 trial published in 2023 in the New England Journal of Medicine. It was double blind and placebo controlled and included adults with obesity who were followed for 48 weeks.

Participants who received the highest doses lost, on average, around a quarter of their body weight during the study period, while the placebo group stayed close to unchanged weight. Nausea and diarrhea were the most common side effects and increased with dose.

The study was designed to find the right dose and examine safety. It was not designed to answer how participants fare in the long run.

The phase 3 trial TRANSCEND-T2D-1 is published in 2026 in The Lancet. It was double blind and placebo controlled and was carried out at 48 clinics in the United States, Mexico and India.

537 adults with type 2 diabetes who were not sufficiently controlled with diet and exercise were randomized to retatrutide 4 mg, 9 mg, 12 mg or placebo once weekly for 40 weeks. The average age was 48.8 years and the average BMI was 35.8.

The average weight change after 40 weeks was 11.5 percent in the 4 mg group, 13.9 percent with 9 mg and 15.3 percent with 12 mg, compared with 2.6 percent in the placebo group. Long-term blood sugar HbA1c fell by 1.69 to 1.94 percentage points, compared with 0.81 percentage points with placebo.

The 15.3 percent figure comes from the published trial's main analysis, the treatment regimen estimand, which counts all participants whether or not they stayed on treatment. Higher figures quoted elsewhere for the same trial, including by the manufacturer, come from a different analysis method and do not come from a different study. We report 15.3 percent because that is the published main analysis.

The most common side effects were mild to moderate gastrointestinal problems that eased over time. Between 2 and 5 percent discontinued treatment due to side effects, against 0 percent in the placebo group. No severe hypoglycemia was reported. Two deaths occurred, both in the 4 mg group, and were assessed as not related to the study drug. The study was funded by the manufacturer Eli Lilly.

The two studies had different participants, different lengths and different purposes. One concerned adults with obesity over 48 weeks, the other adults with type 2 diabetes over 40 weeks.

People with type 2 diabetes often lose less weight than people without diabetes in this type of study. Comparing a quarter against 15.3 percent as if it were the same measurement therefore gives a misleading picture.

All figures are also group averages. Individual participants fell both above and below them, and the results were achieved with an investigational drug under medical follow-up.

The proposed mechanism is that GLP-1 and GIP affect appetite and satiety signals, while the glucagon part is assumed to increase energy expenditure. Together this would give both lower energy intake and higher expenditure.

This is an explanatory model built on the known roles of the hormones. Exactly how much each receptor contributes in humans is not established in the published studies. The mechanism therefore explains why the effect might occur, but it is not in itself a measure of effect.

The design of the registration trials is described in a design paper published in 2025 in Diabetes, Obesity and Metabolism, which covers obesity, obstructive sleep apnea and knee osteoarthritis.

The manufacturer has reported results from the obesity trial TRIUMPH-1 in a press release. A press release is the company's own summary. We have not found any peer reviewed publication of TRIUMPH-1, and figures from it should be read with that reservation.

The reported side effects concern controlled clinical trials with carefully selected participants, medical follow-up and a drug preparation manufactured for clinical testing.

Results from an investigational drug cannot be transferred to a research product used outside a clinical trial. What was given in the studies is not the same thing as a freeze-dried research substance in a vial.

Retatrutide is not approved as a medicine by the FDA or the EMA at the time of writing. The substance is in clinical trials, and the regulators' own registers show the current status.

Retatrutide affects three hormone receptors. In a phase 2 study in obesity, the highest dose groups lost on average around a quarter of body weight over 48 weeks.

In the phase 3 study in type 2 diabetes, the average weight loss was 15.3 percent over 40 weeks with the highest dose against 2.6 percent with placebo, with gastrointestinal problems as the most common side effect.

The figures concern different groups of participants and cannot be compared directly. They concern clinical trials with an investigational drug, not research products in a laboratory setting.