How can you keep the weight off after losing it?

Embargoed until: Publicly released: 2026-05-13 08:00

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In two studies, which were both funded by the makers of the medicines, international researchers say we can likely help ourselves avoid putting weight back on after a weight-loss regimen, an issue commonly seen after cutting the kilos. In the first study, people who were taking the injectable weight loss drugs semaglutide or tirzepatide - called GLP-1 receptor agonists (GLP-1 RAs), such as Ozempic or Wegovy - could prevent their weight from bouncing back by taking a daily oral version of a GLP-1 RA called Orforglipron, which would cut out the need for cold transport and storage of the injectable versions of GLP-1 RAs. In the second study, participants followed a low-calorie diet over eight weeks, and then followed a healthy diet for 24 weeks. Half of the group was given a daily supplement of a pasteurised bacterium, Akkermansia muciniphila Muc^T, or a placebo. The researchers say those who took the probiotic only regained 13.6% of the weight they lost over the initial diet, compared to 32.9% for the group taking the placebo.

News release

From: Springer Nature

Strategies that may help keep weight off

Strategies for maintaining weight lost following injectable treatment or via dieting are described in two unrelated randomised controlled trials published in Nature Medicine. The findings suggest that a daily dose of a GLP-1 receptor agonist administered orally, or a daily bacterial supplement, may help people with overweight or obesity to maintain previously achieved weight loss.

Injectable GLP-1 receptor agonists or dieting can lead to weight loss in people with obesity, but research has shown that weight lost is often recovered when treatment ends. Orforglipron is a GLP-1 receptor agonist administered orally that is under investigation for obesity and type 2 diabetes. Its use may avoid some practical difficulties linked to injections, including transportation and cold storage. Separately, treatments that target the gut microbiome are also being investigated to help with weight-loss maintenance.

In a double-blind, randomised phase 3b trial, Louis Aronne and colleagues studied 376 participants (mean age of 48.6 years) in the US who had already completed 72 weeks of injectable treatment with GLP-1 receptor agonists tirzepatide or semaglutide. Once daily over the next 52 weeks, participants received either orforglipron or a placebo. In the group previously treated with tirzepatide, participants assigned to receive orforglipron maintained 74.7% of their earlier weight loss at week 52, compared with 49.2% in the placebo group. In the group previously treated with semaglutide, the figures were 79.3% and 37.6%, respectively. The most common side effects were gastrointestinal and were mostly mild to moderate in severity .

In a separate paper, Ellen Blaak and colleagues studied 90 adults in the Netherlands (mean age of 51.8 years) with overweight or obesity in a double-blind, randomised controlled trial. Participants first followed a low-calorie diet over 8 weeks to lose weight. 84 of these participants (who lost 8% or more of their body weight) then followed a healthy diet for 24 weeks and were assigned to either take a daily supplement of the pasteurized bacteria Akkermansia muciniphila Muc^T or a placebo. Those who received the bacteria supplement regained 13.6% of the weight they initially lost in the first phase, while those who received the placebo regained 32.9%. Participants who took the supplement achieved a greater overall weight loss of 3.1 kilograms from the start of the study than those receiving placebo. The supplement group also showed better preservation of insulin sensitivity, and no serious treatment-related side effects were reported during the study period.

Together, these studies suggest that initial weight loss may be maintained either by switching from injectable therapy to orforglipron or by using a gut microbiome-targeting supplement after diet-induced weight loss. However, both sets of authors note the short-term nature of the studies and the limited diversity of the populations studied. Further research will be needed to determine how these approaches might be used in longer-term obesity care.

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Research Springer Nature, Web page Paper 1 - The URL will go live after the embargo ends

Research Springer Nature, Web page Paper 2 - The URL will go live after the embargo ends

Journal/
conference: Nature Medicine

Research: Link to Paper 1 | Paper 2

Organisation/s: Weill Cornell Medicine, USA | Maastricht University Medical Center+, Maastricht, the Netherlands

Funder: Paper 1 - This study was funded by Eli Lilly and Company. We thank all investigators, research team members and, most of all, the study participants. We thank M. Müller, E. Seth and C. Khouli (Eli Lilly and Company) for writing and editorial contributions. The funder of this study was involved with study design, data collection, analysis, interpretation and writing of this report. The authors had full access to the data, and all contributed to and approved this manuscript for publication. Paper 2 - The Akkermansia Company SA (Mont-Saint-Guibert, Belgium) provided the intervention and placebo product. E.E.B. obtained funding for this study from The Akkermansia Company SA.

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