By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
The ATTAIN-MAINTAIN trial: keeping weight off after weight-loss injections
The ATTAIN-MAINTAIN trial looked at a question that concerns many patients: can you switch from an injection to a pill and keep the weight off? According to the results, the answer is encouraging. Patients who switched to the daily pill orforglipron kept most of their weight loss for a year. In contrast, those who switched to placebo regained a noticeable amount of weight.
In recent years, drugs such as Wegovy and Mounjaro have produced weight loss we had never seen before. Yet precisely after that success, the hardest question comes up: how do you keep the weight off over time? This question is especially relevant now. Orforglipron was approved by the FDA, the U.S. Food and Drug Administration, in April 2026 under the brand name Foundayo. Since September 2026, it has also been available in Israel.
The body fights weight loss
Regaining weight is not a personal failure. Rather, it is an expected biological response. When a person loses weight, levels of the fullness hormone leptin go down. At the same time, the hunger hormone ghrelin goes up. In addition, the body lowers its energy expenditure. In other words, the body tries to return to its previous set point.
That is why, on many diets, people lose weight but find it very hard to keep it off. You can read more about this process in my article on maintaining weight after major weight loss.
Obesity is a chronic disease, not a temporary project
The message of the new studies is clear. Treating obesity is similar to treating high blood pressure, diabetes or asthma. It is a chronic disease that needs ongoing treatment, not a short course.
For example, in the SURMOUNT-4 trial, patients lost an average of 20.9% of their body weight on tirzepatide. Then some of them were switched to placebo. Within 52 weeks, they regained 14.0% of their weight. Meanwhile, those who stayed on tirzepatide lost another 5.5%. The SURMOUNT-MAINTAIN trial, published in The Lancet in May 2026, reached a similar conclusion. So when an effective treatment stops, weight goes up, and blood sugar, blood pressure and blood lipids also get worse.
What is orforglipron?
Orforglipron is an oral GLP-1 receptor agonist. Put simply, it works like GLP-1 injections, but it comes as a daily pill. Unlike the semaglutide pill, it is not a protein and does not require special dosing conditions. You can take it at any time of day, with or without food, and with no limits on drinking.
The researchers describe it as a treatment that can easily be scaled up to large populations and many countries. The advantage for patients is clear. Many people fear injections, struggle to stay on treatment or simply prefer a pill. As a result, switching to a pill may help with long-term maintenance. You will find a full guide in my article on Foundayo treatment.
How the ATTAIN-MAINTAIN trial was designed
The trial included 376 patients who had completed the SURMOUNT-5 trial. In that earlier trial, they received tirzepatide or semaglutide for 72 weeks. They were then randomly assigned to orforglipron or placebo for 52 weeks. The trial results were presented at the European Congress on Obesity (ECO 2026) and published in Nature Medicine in May 2026.
ATTAIN-MAINTAIN trial results
Patients who switched from tirzepatide to orforglipron kept 74.7% of their weight loss. In the placebo group, they kept only 49.2%. Similarly, those who switched from semaglutide to orforglipron kept 79.3% of their weight loss, compared with 37.6% on placebo.
According to the company’s announcement, those who switched from semaglutide to the pill kept almost all of their weight loss, apart from 0.9 kg on average. For those who switched from tirzepatide, the gap was much larger, about 5 kg. The researchers suspect the reason is the greater potency of tirzepatide. Another interesting finding is that both groups ended at exactly the same average weight, 95.9 kg.
Not just weight: metabolic health held steady too
The benefit went beyond the number on the scale. For example, in those who switched to the pill, HbA1c, the average blood sugar over the past three months, fell from 5.6% to 5.2% during the injection phase. After a year on the pill, it stayed at 5.2%. In addition, waist circumference changed by only about 1 to 3 cm. A similar pattern was seen in insulin levels, fasting blood sugar, blood lipids and blood pressure. In other words, these drugs are not just “weight-loss drugs.” They affect many systems in the body.
What about side effects?
The side effects were similar to those of the GLP-1 family: nausea, constipation, diarrhea and vomiting. Most were mild to moderate. The rate of stopping treatment because of side effects ranged from 4.8% to 7.3%. The direct switch from the injection to the 12 mg dose of the pill was well tolerated. Also, the researchers found no liver safety signal.
The ATTAIN-MAINTAIN trial and a new direction in obesity medicine
The new studies shift the question from “How much did you lose?” to “How do you protect your health over the years?” Perhaps we will soon see a new treatment model. In the first stage, a powerful injection leads to significant weight loss. In the second stage, a daily pill locks in the result.
However, it is important to remember the trial’s limitations. It lasted only one year. Moreover, it had no group that stayed on the injection, so a direct comparison is not possible. The decision to switch should be personal and made with your doctor. For a comparison of the two pills now available, see my article on the Wegovy pill and Foundayo.
Bottom line
Obesity is a biological, chronic and long-lasting disease. When it is treated properly, it is possible both to lose weight and to keep the results. The ATTAIN-MAINTAIN trial shows that switching from an injection to a pill can be a practical way to do this. The future of obesity medicine will probably rely on long-term maintenance that is convenient and tailored to each person. You can learn more about orforglipron in this video.
The information in this article is general and does not replace personal medical advice.
Frequently asked questions: keeping weight off after medication
Why is it so hard to keep weight off after losing it?
The body reacts to weight loss as if it were a state of scarcity. Hunger hormones rise, the feeling of fullness drops and metabolism slows down. Therefore, even people with strong willpower may feel hungry and regain weight.
Is regaining weight after a diet a personal failure?
No. Obesity is a chronic biological disease. Regaining weight is a well-known physiological response, not a sign of weakness.
Do I have to stay on medication for years?
For many patients, yes. Like high blood pressure or diabetes, obesity usually needs long-term treatment to maintain the results.
What did the ATTAIN-MAINTAIN trial show?
Patients who switched from injections to orforglipron kept 74.7% to 79.3% of their weight loss over one year. That is a large gap compared with placebo.
Questions about the orforglipron pill
What is orforglipron?
It is a daily pill from the GLP-1 family, sold as Foundayo. It does not require refrigeration, fasting or limits on drinking.
Can a pill be as effective as an injection?
According to the data, the pill preserved most of the weight loss well. Still, after tirzepatide, some patients regained a little weight.
Did patients regain weight after switching to the pill?
Some regained a little. In those who switched from semaglutide, the average gain was about one kilogram over the year, and in those who switched from tirzepatide, about 5 kg.
What happened to metabolic health?
Average blood sugar, blood lipids, blood pressure and waist circumference barely changed over the year.
What side effects were seen?
Nausea, constipation, diarrhea and sometimes vomiting. In most cases, they were mild to moderate and eased over time.
Will everyone switch from injections to pills in the future?
There is no clear answer yet. We will probably see personalized treatment: some people will start with an injection and switch to a pill, while others will stay on the injection.
Do obesity medications affect only weight?
No. They also affect heart risk, blood sugar, fatty liver, chronic inflammation and quality of life.
What is the most important message?
Obesity treatment does not end with weight loss. The real challenge is protecting your health over the years, with tailored treatment, a healthy lifestyle and regular follow-up.
References
Lilly’s orforglipron helped people maintain weight loss after switching from Zepbound or Wegovy
FDA approves orforglipron, an oral GLP-1, for adults with obesity
The studies were funded by Eli Lilly, the drug’s manufacturer.
