A three hormone shot cut a quarter of body weight in 48 weeks, trial finds

Every few months a news story reports a new record for weight loss. Behind each one sits an easy question to skip: has anyone outside the company checked the numbers? For one new weekly shot, the honest answer is mostly no [1][3].

The one trial of the shot printed in a journal ran for 48 weeks, a little under a year. Adults on the highest amount lost 24.2 percent of their body weight on average. That is about a quarter. People given a placebo, a look alike shot with no medicine in it, lost 2.1 percent [1].

One thing is worth saying early. The even bigger numbers now going around come from a larger trial that no journal has printed. So far they exist only as a company announcement and a talk at a medical meeting, which outside scientists have not checked [2][3].

The shot is called retatrutide. The printed trial was led by Ania Jastreboff of the Yale School of Medicine and appeared in the New England Journal of Medicine in 2023. The drug company Eli Lilly, which makes the shot, paid for the trial, and several of the authors work there [1].

Why is this shot different? Many newer weight loss medicines copy hormones the gut releases after a meal. They work through receptors, which act like tiny switches on the outside of cells, each one flipped by a single hormone. Older shots flip one or two of these switches. This one is built to flip three. The third answers to glucagon, a hormone tied to how the body burns energy and how the liver handles fat. Nobody has shown yet whether that third switch explains the results [1][6].

The printed trial was a phase 2 trial, the middle step of testing a drug in people. It signed up 338 adults who had obesity, or extra weight plus a related health problem. Chance decided, like a coin flip, who got one of several amounts and who got the placebo [1].

On the top amount, 83 in every 100 people lost at least 15 percent of their weight. On the placebo, 2 in 100 did. The researchers summed it up in one line [1]:

In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.

Jastreboff and colleagues, New England Journal of Medicine, 2023 [1]

In plain words, the shot led to a lot of weight loss over 48 weeks. The most common side effects were in the gut, such as feeling sick. They grew with the amount and were mostly mild or moderate. Heart rate also rose with the amount, peaking at 24 weeks [1].

So what about the bigger trial?

The larger trial is called TRIUMPH-1, listed in the public trial registry as NCT05929066. The company says it included 2,339 people for 80 weeks, about a year and a half. It announced the results in May 2026 and says fuller results will go to journals later. The registry lists the trial as finished, with no results posted [2][3].

The announcement gives two main numbers, and news stories often pick just one. Counted as if everyone stayed on the shot as planned, people on the top amount lost 28.3 percent of their weight, against 2.2 percent on the placebo. Counted the stricter way, which keeps everyone in the group chance put them in, even people who stopped early, it was 25.0 percent against 3.9 percent [3][4].

Neither number is wrong. The first asks what the shot does when people take it as planned. The second asks what happens to a whole group that is offered it. The company led with the higher number, which is why two news stories about the same trial may not match [3][4].

The announcement adds that 45.3 percent of people on the top amount lost at least 30 percent of their weight. On the placebo, 0.5 percent did, about 1 person in 200. Then 532 people who started with a body mass index, a number that compares weight to height, of 35 or more kept going to 104 weeks. On the top amount they lost 30.3 percent on average. But for that part, everyone who had been on the placebo was moved onto the drug, so there is no comparison group [3].

The same program is also testing the shot in people with sleep apnea, where breathing stops and starts during the night. It is testing it in knee osteoarthritis too, where the joint wears down and hurts. Across four late stage trials, it plans to include more than 5,800 people [6]. A separate trial in type 2 diabetes, a disease where blood sugar runs too high, is listed as finished with no results posted [5].

Where do things stand?

The shot is not an approved medicine anywhere. Health Canada, the United States Food and Drug Administration and similar agencies have not reviewed it. The company does not expect to ask for approval before late 2027 [7].

This record does not show how the shot compares with weight loss shots already in use, since these trials tested it only against a placebo. It does not show what happens after people stop. And the biggest numbers have not yet been through peer review, where scientists who did not run a study check it before a journal prints it. What the record does show is narrower. In one checked trial, adults on a weekly shot lost about a quarter of their weight in under a year, far more than on a placebo [1][3][4].