ORFLORGLIPRON pills have achieved clinically meaningful maintenance of weight loss in patients who discontinued glucagon-like peptide-1 receptor agonist (GLP-1) injectable therapies, in new findings from the ATTAIN-MAINTAIN trial.
Participants were more able to maintain reductions in weight if they switched to the once-daily oral GLP-1, rather than a placebo.
The trial included 376 participants in the US, who had been previously treated with injectable tirzepatide or semaglutide for more than a year and had experienced weight loss.
They were subsequently administered orforglipron or placebo for a year.
Tirzepatide
Those who took oral orforglipron after discontinuation of injectable tirzepatide kept off 74.7% of their earlier weight loss at week 52 of the trial.
Alternatively, those in the placebo group maintained only 49.2% of their prior weight loss, resulting in a treatment difference of around 25.5% weight reduction.
Semaglutide
A similar, but more substantial, pattern was observed in those who had stopped injecting semaglutide.
With orforglipron, participants maintained 79.3% of their earlier weight loss, compared with 37.6% in the placebo cohort.
This resulted in an estimated treatment difference of 41.7% after a year.
Clinical Implications
Participants treated with oral orforglipron saw average drops in body weight from week zero to 52 of the trial of approximately 5kg and 1kg in the tirzepatide and semaglutide cohorts, respectively.
Researchers noted that it is often incorrectly thought, by patients as well as some clinicians, that obesity management medications can be discontinued after achieving initial weight loss.
However, discontinuation after intentional weight loss could lead to weight cycling and a loss of cardiometabolic benefits.
Researchers pointed to the potential of orforglipron a globally scalable option for stabilising weight changes after injectable GLP-1 therapy.
Oral orforglipron is available in the US and could soon be rolled out in the UK.
Reference
Aronne LJ et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med. 2026;10.1038/s41591-026-04386-7.
Featured image: Andreas Prott on Adobe Stock
