A daily weight loss pill helped adults lose about a tenth of their weight

For most of the past ten years, the newest weight loss medicines have come as a shot. A small pen goes into the skin of the belly or thigh, once a week. Now two large trials have tested a medicine that acts on the same target in the body, in a pill swallowed once a day.

The bigger trial ran for 72 weeks, which is almost a year and a half. Adults with obesity who took the highest amount lost 11.2 percent of their body weight on average. That is about a tenth. People who took a look alike pill with no medicine in it lost 2.1 percent [1].

One thing is worth saying early. This pill has never been tested side by side with the shots, so nobody can yet say which works better. Both trials compared it only with the fake pill [1][2].

The pill is called orforglipron. The first trial, known as ATTAIN-1, was led by Sean Wharton of McMaster University in Hamilton, Ontario, and was published in the New England Journal of Medicine in 2025. The drug company Eli Lilly, which makes the pill, paid for the trial, and several of the authors work there [1].

Why does a pill matter? The weekly shots copy a hormone the gut releases after a meal, called GLP-1. To do that, they are built as chains of amino acids, the small building blocks of proteins. The stomach breaks chains like that apart, the same way it breaks down food, so they have to be injected. Orforglipron is different. It is a small molecule made by ordinary chemistry, which lets it survive being swallowed while still acting on the same spot on cells. That spot is called the GLP-1 receptor, a kind of switch on the cell that the hormone flips [1][2].

The first trial signed up 3,127 adults who had obesity but not diabetes. Chance decided, like a coin flip, who got one of three amounts of the pill and who got the fake pill. Everyone also got advice on food and exercise. The researchers counted every person in the group they started in, even people who later stopped taking the pill, which keeps the results honest [1].

Weight fell more with each step up in amount: 7.5, 8.4 and 11.2 percent, against 2.1 percent on the fake pill. On the highest amount, more than half of the people lost at least a tenth of their body weight. On the fake pill, about one in eight did. Waist size, blood pressure and some blood fats also improved more on the pill [1].

The researchers summed up the trial this way:

In adults with obesity, 72-week treatment with orforglipron led to significantly greater reductions in body weight than placebo; the adverse-event profile was consistent with that of other GLP-1 receptor agonists.

Wharton and colleagues, New England Journal of Medicine, 2025 [1]

In plain words, the pill beat the fake pill, and its side effects looked like those of the weekly shots. The most common problems were in the gut, such as feeling sick, and most were mild or moderate. Between about 5 and 10 in every 100 people on the pill stopped because of side effects, against about 3 in 100 on the fake pill [1].

A second trial, ATTAIN-2, was published in The Lancet. It tested the same pill in 1,613 adults who carried extra weight and also had type 2 diabetes, a disease where blood sugar runs too high. It ran at 136 sites in ten countries. Weight loss there was smaller: 9.6 percent on the highest amount, against 2.5 percent on the fake pill. That gap between the two trials is common with medicines of this kind, and it is a good reminder that one headline number never fits everyone. Ten people died during this trial, six taking the pill and four taking the fake pill [2].

What comparison has not been done?

So how does the pill compare with the shots? For now, nobody knows, because no trial has tested them side by side. The only study so far lines up results from separate trials using math, and most of its authors worked for the company that makes a rival pill. Its own authors describe it as a stand in until a real head to head trial is run:

These findings provide insight into the comparative effectiveness and tolerability in the absence of head-to-head clinical trials.

Michalak and colleagues, Diabetes, Obesity and Metabolism, 2026 [3]

This work also does not show anything about heart attacks, strokes or how long people live, since neither one measured them. And 72 weeks is too short to say what happens after people stop. The public record of the first trial shows it is still going on, though no longer taking new people [4]. What the two trials do show is narrower but still worth knowing. A pill swallowed once a day, rather than a weekly shot, led to clearly more weight loss than a fake pill in adults with obesity, with or without diabetes [1][2][3].