Medicine: Strategies that may help keep weight off (Nature Medicine)
13 May 2026
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 MucT 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.
- Article
- Open access
- Published: 13 May 2026
Aronne, L.J., Horn, D.B., le Roux, C.W. et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04386-7
- Article
- Published: 13 May 2026
Mount, S., Canfora, E.E., Jocken, J.W. et al. Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04394-7
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