Injectable GLP-1 drugs have transformed obesity treatment, but what happens when patients stop injecting? A phase 3b trial, ATTAIN-MAINTAIN, led by Louis Aronne of Weill Cornell Medicine's Comprehensive Weight Control Center and published in Nature Medicine, offers one answer: a once-daily pill can preserve most of the gains. The trial enrolled participants who had reached substantial, plateaued weight loss on weekly injectables in the earlier SURMOUNT-5 study.
In the new trial, 205 people previously on tirzepatide and 171 on semaglutide were randomised to the oral GLP-1 drug orforglipron or placebo for 52 weeks. Tirzepatide switchers on the pill kept a mean 74.7 per cent of their weight loss, against 49.2 per cent on placebo; semaglutide switchers kept 79.3 per cent versus 37.6 per cent. Participants also maintained most cardiometabolic improvements, including waist circumference, blood pressure, blood sugar and cholesterol, with side effects that were mild to moderate and gastrointestinal.
The pattern reflects mechanism: tirzepatide acts on two hormonal targets and produces greater initial loss, which appears harder to hold with a single-target pill, while semaglutide and orforglipron share one target. The study, sponsored by Eli Lilly, is described as the first of its type to examine longer-term maintenance with an oral GLP-1 after injectables, a question of growing importance as patients weigh convenience, cost and the chronic nature of obesity.