Oral Ribupatide Produces Up to 12% Weight Loss in Phase 2 Obesity Trial

Once-daily oral ribupatide, a dual GLP-1/GIP receptor agonist, produced clinically meaningful weight loss with a generally favorable tolerability profile in a phase 2 randomized trial conducted in adults with obesity in China, according to topline results announced by Hengrui Pharma and Kailera Therapeutics.

In the 26-week, multicenter, double-blind study (HRS9531-T-201; NCT06841445), participants receiving oral ribupatide achieved mean placebo-adjusted weight reductions of up to 12.1%, with no observed plateau in weight loss at the highest evaluated doses. The trial enrolled 166 adults with obesity (BMI ≥28 kg/m²) without type 2 diabetes, who were randomized to once-daily oral ribupatide 10 mg, 25 mg, 50 mg, or placebo.

Efficacy outcomes. Using the prespecified efficacy estimand, mean percentage weight loss at week 26 was 6.9% with 10 mg, 12.1% with 25 mg, and 12.1% with 50 mg, compared with 2.3% with placebo. Based on the treatment policy estimand, corresponding weight reductions were 6.7%, 11.9%, and 11.4%, respectively, compared to 2.1% with placebo.

Higher proportions of participants achieved clinically relevant weight-loss thresholds with ribupatide. At the 25-mg dose, 59.1% achieved at least 10% weight loss and 38.6% achieved at least 15% weight loss at week 26. At the 50-mg dose, 52.5% and 37.5% of participants achieved at least 10% and 15% weight loss, respectively.

Safety and tolerability. Oral ribupatide demonstrated a safety profile consistent with GLP-1–based therapies. Most treatment-emergent adverse events were mild to moderate and gastrointestinal in nature. Rates of vomiting were 2.4% with 10 mg, 11.4% with 25 mg, and 7.5% with 50 mg, while nausea occurred in 11.9%, 22.7%, and 20.0% of participants, respectively.

No permanent treatment discontinuations or dose reductions due to nausea, vomiting, diarrhea, or constipation were reported.

Clinical context and next steps. “These data highlight the potential to deliver a differentiated oral medication for the treatment of obesity,” Zi Ye, MD, senior medical director for metabolic diseases clinical development at Hengrui, said in a press release, noting plans to advance oral ribupatide rapidly into phase 3 trials in China.

Kailera plans to initiate a global phase 2 trial of oral ribupatide in 2026, while continuing late-stage development of an injectable formulation within its KaiNETIC phase 3 program. Injectable ribupatide has previously demonstrated mean weight loss of 23.6% at 36 weeks in a separate trial conducted in China, compared with 1.8% with placebo.

For primary care clinicians, the emergence of oral incretin-based therapies may have implications for patient acceptance, adherence, and earlier intervention in obesity management, although longer-term efficacy, safety, and real-world outcomes remain to be established.

Hengrui plans to present the full phase 2 oral ribupatide dataset at an upcoming scientific meeting.

Reference: Kailera Therapeutics and Hengrui Pharma Report Positive Topline Data from Phase 2 Obesity Trial of Oral Ribupatide. News release. Kailera Therapeutics. February 10, 2026. Accessed February 10, 2026. https://www.globenewswire.com/news-release/2026/02/10/3235172/0/en/Kailera-Therapeutics-and-Hengrui-Pharma-Report-Positive-Topline-Data-from-Phase-2-Obesity-Trial-of-Oral-Ribupatide.html