Most weight loss achieved with injectable obesity drugs can be maintained by switching to daily oral orforglipron, according to a study published in Nature Medicine and presented at the European Congress on Obesity (ECO2026) in Istanbul. The research, led by Dr. Louis J. Aronne of Weill Cornell Medicine, followed patients who had previously lost weight using tirzepatide or semaglutide in the SURMOUNT-5 trial. Participants were then randomly assigned to receive orforglipron or a placebo for 52 weeks.
Across both groups, those taking orforglipron retained a majority of their weight loss. In one group, they maintained 79.3% of the weight reduction achieved earlier, compared to 37.6% in the placebo group. Another cohort saw 79.3% of weight loss preserved with orforglipron, versus 37.6% without it. The drug also helped sustain improvements in cholesterol, blood pressure, and blood sugar control observed during the initial trial.
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Safety profiles were similar between the orforglipron and placebo groups, with no significant differences in adverse events. A rescue protocol was introduced at week 24: participants on placebo who regained 50% or more of their weight loss were switched to orforglipron. This aimed to prevent the loss of cardiometabolic benefits seen in the earlier phase of the study.
On average, participants taking orforglipron regained about 5 kg (5%) in one group and 1 kg (1%) in another over the year, compared to greater weight regain in the placebo group. The study authors noted that transitioning from tirzepatide—dual GIP/GLP-1 agonist—to orforglipron (single GLP-1 agonist) might result in more weight regain than switching from semaglutide to orforglipron, though further research is needed.
“A small degree of weight regain while maintaining the majority of loss may be clinically acceptable,” the authors said, especially if switching to an oral pill offers convenience over injections. They emphasized that stopping obesity medications after initial success can lead to weight cycling and worsened cardiometabolic health, similar to discontinuing treatments for hypertension or high cholesterol.
The trial suggests that orforglipron could serve as a viable option for long-term weight management, particularly for patients who prefer oral medication over injections, or due to cost, storage needs, or other preferences. The findings highlight the importance of shared decision-making in obesity care and the potential of transitioning from injectable to oral therapies to improve treatment persistence.
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