Can a pill keep the weight off after using a GLP-1?

Here’s a question that almost every patient on a GLP-1 medication eventually asks: what happens when I stop? We know from experience that the weight tends to come back. So this study asks a practical follow-up – if someone has lost weight on an injectable GLP-1, can switching to a once-daily pill help them hold onto that weight loss?

This is the ATTAIN-MAINTAIN trial, a double-blind, randomized study. The participants had already lost a substantial amount of weight over 72 weeks on an injectable GLP-1 in an earlier trial called SURMOUNT-5 – either tirzepatide or semaglutide. Rather than continue the injection, they were randomized to either a once-daily oral pill called orforglipron, or to placebo, and followed for another year. In all, 376 people were included across the two groups. The mean age was about 48, roughly two-thirds were women, and by the start of this maintenance phase they had already brought their weight down to an average of around 90 kg.

The main question was how much of their hard-won weight loss they could keep. Among those who had reached a stable weight, the people who switched to the orforglipron pill maintained about 75% of their weight loss in the former-tirzepatide group and about 79% in the former-semaglutide group. In the placebo groups, only about 49% and 38% of the weight loss was maintained. Put simply, stopping treatment altogether gave back a much larger share of the weight, while the daily pill preserved most of it – a difference that was statistically significant in both groups. The pill also held onto improvements in things like waist circumference, blood pressure, and lipids.

There’s a telling detail in how the trial ran. So many people in the placebo group regained weight that the study allowed them to start orforglipron as “rescue” therapy if they regained at least half of what they had lost. About two-thirds of the placebo patients who hit that mark took the rescue medication, and by the one-year point only a handful of placebo participants were still going without it. That alone says something about what happens when these medications are simply stopped.

As you would expect with a GLP-1, the main side effects were gastrointestinal – nausea, constipation, vomiting, and diarrhea – and they were mostly mild to moderate. Nausea was the most common, and very few people stopped the drug because of side effects.

The bottom line: for patients who have lost weight on an injectable GLP-1, switching to a once-daily oral pill may let them hold onto most of that loss without staying on injections. That’s an appealing idea. A pill that doesn’t require refrigeration, needles, or even food and water restrictions could be much easier for patients to stay on, and much easier to distribute around the world, than a weekly shot.

A few honest caveats. There was no arm that simply continued the injectable medication, so we can’t say whether the pill maintains weight as well as staying on the shot – only that it clearly beats stopping. The trial lasted one year, all of the sites were in the United States, and because so many placebo patients needed rescue therapy, the clean comparison gets a little blurry toward the end.  

In our CME we cover the broader GLP-1 story, including our comparison of tirzepatide and semaglutide for weight loss. This study adds a new chapter to that conversation – not just how to help patients lose the weight, but how to help them keep it off, and the growing possibility of doing that with a pill.

Reference: Aronne LJ, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med 2026; 32:2679-2687.