Ribupatide

What is Ribupatide?#

Ribupatide (HRS9531/KAI-9531) is an investigational dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist peptide being developed for the treatment of obesity and overweight. It is developed by Hengrui Pharma in Greater China and Kailera Therapeutics for global markets.

Ribupatide is notable for being developed in both injectable and oral formulations, providing flexibility in delivery. The injectable formulation is administered once weekly via subcutaneous injection, while the oral formulation is taken once daily. Both formulations have demonstrated substantial weight loss in Phase 2 clinical trials, with the injectable achieving up to 21.1% placebo-adjusted weight loss and the oral achieving up to 12.1% weight loss.

The global Phase 3 clinical program (KaiNETIC) for injectable ribupatide has been initiated, with first participants randomized. Hengrui is also advancing oral ribupatide to Phase 3 in China.

Mechanism of Action#

Ribupatide activates both the GLP-1 and GIP receptors, producing complementary metabolic effects similar to tirzepatide.

Dual Incretin Agonism#

• GLP-1 receptor activation: Stimulates glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying, and activates central appetite-suppressing pathways in the hypothalamus and brainstem
• GIP receptor activation: GIP receptor agonism is hypothesized to enhance insulin secretion, improve lipid metabolism, modulate fat distribution, and contribute to appetite regulation through distinct neural pathways
• Complementary weight loss mechanisms: The dual receptor approach may produce greater weight loss than GLP-1 agonism alone by engaging additional metabolic and appetite-regulating pathways

Pharmacokinetics#

The injectable formulation has a half-life suitable for once-weekly subcutaneous dosing. Specific pharmacokinetic parameters have not been fully disclosed. The oral formulation is designed for once-daily administration, with absorption characteristics appropriate for daily oral dosing.

Research Overview#

Ribupatide has been evaluated in Phase 2 trials for both the injectable and oral formulations, with particularly impressive weight loss results. The injectable 8 mg dose demonstrated placebo-adjusted weight loss of 21.1% at 36 weeks without evidence of plateau. The oral 50 mg dose achieved 12.1% weight loss at 26 weeks. Phase 3 clinical trials are underway for both formulations.

Hengrui has also completed Phase 3 obesity trials in China, reporting significant weight loss results that position ribupatide as a competitive dual agonist in the metabolic therapy space.

Important Considerations#

• Investigational compound not approved by any regulatory agency
• Phase 3 trials (KaiNETIC program) in progress globally
• Safety profile consistent with GLP-1/GIP receptor agonist class
• No cardiovascular outcomes data available
• No head-to-head comparison with tirzepatide

Key Research Findings#

Efficacy and Safety of HRS9531, a Novel Dual GLP-1/GIP Receptor Agonist, in Obese Adults - A Phase 2 Trial, published in Diabetes (ADA Poster) (Hengrui Pharma investigators, 2024):

• The study demonstrated mean weight loss of 22.8% at 36 weeks
• The study demonstrated placebo adjusted weight loss of 21.1%

Phase 2 Obesity Trial of Oral Ribupatide in Chinese Adults, published in Press release (Globe Newswire) (Hengrui Pharma and Kailera Therapeutics investigators, 2026):

• The study showed mean weight loss of 12.1% at 26 weeks with the 25 mg and 50 mg oral doses

Related Reading#

• Ribupatide research studies and evidence
• Ribupatide dosing protocols
• Ribupatide side effects profile
• Semaglutide research guide
• Tirzepatide research guide