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Oral semaglutide 25 mg for weight loss: Evidence from a 71-week trial

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Created On: 20/01/2026

Overweight and obesity remain global health challenges with significant metabolic and quality-of-life consequences.

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Key take away

In adults with overweight or obesity, oral semaglutide 25 mg daily produces significant weight reduction and improves physical function.

Background

Overweight and obesity remain global health challenges with significant metabolic and quality-of-life consequences. Sean Wharton et al. aimed to evaluate the efficacy and safety of once-daily oral semaglutide 25 mg, a novel non-injectable therapy, in promoting weight loss and enhancing physical function.

Method

This 71-week, randomized controlled trial enrolled 307 adults without diabetes across 22 sites in four countries. Volunteers had a body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² with a minimum of one obesity-related complication. They were assigned in a 2:1 ratio to receive either once-daily oral semaglutide 25 mg (n=205) or placebo (n=102), alongside structured lifestyle interventions.

The study’s coprimary endpoints at week 64 were percentage alteration in body weight and achieving ≥5% weight loss, while secondary endpoints measured higher weight-loss thresholds (≥10%, ≥15%, ≥20%) and improvements in physical function using the impact of weight on quality of life-lite clinical trials version (IWQOL-Lite-CT). Safety and adverse events were systematically monitored throughout the trial.

Result

The findings revealed that oral semaglutide 25 mg produced clinically meaningful weight loss. Those receiving oral semaglutide lost an average of 13.6% of their baseline body weight by week 64, compared with 2.2% in the placebo group, representing a -11.4% point difference (P<0.001).

Remarkably, more participants on semaglutide achieved weight reductions of ≥5%, ≥10%, ≥15%, and ≥20% (all P < 0.001) and exhibited improved physical function scores on the IWQOL-Lite-CT scale (P < 0.001). Gastrointestinal events were more frequent with semaglutide than placebo (74% vs. 42%), but overall, the treatment was well-tolerated.

Conclusion

Once-daily oral semaglutide 25 mg induced substantial body-weight loss and improved functional outcomes, highlighting its promise as a non-injectable weight-management option.