Obesity remains a major cardiometabolic risk factor, and development of effective oral incretin-based therapies continues to expand treatment options beyond injectable agents. Findings presented at the ADA Scientific Sessions 2026 evaluated the efficacy and safety of oral ribupatide, a glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist, in adults with obesity without diabetes.

This 26-week randomized trial enrolled adults with a body mass index (BMI) of 28-40 kg/m². Participants were randomized in a 1:1:1:1 ratio to receive oral ribupatide 10 mg, 25 mg, 50 mg, or placebo. The primary endpoint was percentage change in body weight from baseline at week 26. Mean baseline body weight was 92.6 kg and mean BMI was 33.3 kg/m².

Findings

• Least squares mean weight reduction at week 26 was 6.7%, 11.9%, and 11.4% with ribupatide 10 mg, 25 mg, and 50 mg, respectively, compared with 2.1% with placebo (P=0.0023, P<0.0001, and P<0.0001).
• The 50 mg group demonstrated steeper weight reduction after week 8 compared with the 25 mg group, with no observed weight-loss plateau through week 26 in either group.
• Across ribupatide groups, up to 77.5% of participants achieved at least 5% body weight reduction, 59.1% achieved at least 10% reduction, and 38.6% achieved at least 15% reduction.
• Ribupatide groups showed greater reductions in waist circumference, blood lipids, uric acid, and blood pressure compared with placebo.
• The most common adverse events were nausea, diarrhea, and vomiting. Events were mostly mild to moderate, and no gastrointestinal adverse events led to treatment discontinuation or dose down-titration. No adverse events of special interest occurred.

This study showed that oral ribupatide produced substantial weight reduction over 26 weeks in adults with obesity without diabetes, with additional improvements in multiple cardiometabolic parameters. Gastrointestinal adverse events were consistent with the incretin therapy class and were generally manageable within the study period.