HRS9531 (Ribupatide)

A once-weekly GLP-1/GIP receptor dual agonist peptide from Jiangsu Hengrui, licensed outside Greater China to Kailera Therapeutics as KAI-9531, with Chinese phase 3 weight-loss and diabetes data, two marketing applications under NMPA review, a fully enrolled global phase 3 program and no approval anywhere.

Also referenced as: HRS-9531, KAI-9531

Also appears in: Metabolic

COA Public product evidence No certificate records are bound to a tracked HRS9531 (Ribupatide) product page A record counts here only when a vendor publishes a certificate against one of its own tracked HRS9531 (Ribupatide) product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

---

What is HRS9531 (Ribupatide)?

HRS9531, now assigned the nonproprietary name ribupatide, is a chemically synthesized polypeptide that activates both the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor, the same two-receptor pharmacology as tirzepatide. It was discovered by Jiangsu Hengrui Pharmaceuticals, whose subsidiary Fujian Shengdi Pharmaceutical sponsors the Chinese trials, and is formulated for once-weekly subcutaneous injection, with a terminal half-life of about seven to eight days in humans (He et al., Diabetes, Obesity and Metabolism, 2026). A once-daily oral tablet of the same peptide is in separate development.

The compound draws attention because its Chinese phase 2 and phase 3 trials reported mean weight loss in the range that tirzepatide produced in its own registration trials, although over shorter treatment periods and only in cross-trial comparison. In May 2024 Hengrui licensed it, together with its other GLP-1-based candidates, to the United States company Kailera Therapeutics for all territories outside mainland China, Hong Kong, Macau and Taiwan; Kailera develops it under the code KAI-9531. Ribupatide is not a research-market product; it appears, if at all, in occasional reagent-catalog listings.

How it works

• Dual GLP-1 and GIP receptor agonism. In cell-based functional assays ribupatide activates signaling at both receptors, and in diet-induced obese mice it reduced body weight and cumulative food intake over 28 days compared with vehicle (He et al., Diabetes, Obesity and Metabolism, 2026). GLP-1 receptor activation increases glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and reduces appetite through hypothalamic and hindbrain circuits (Drucker, Cell Metabolism, 2018;27(4):740–756). GIP receptor co-activation is thought to add to weight loss through central appetite effects and adipose-tissue actions and may blunt GLP-1-related nausea, although the contribution of the GIP component remains debated (Samms et al., Trends in Endocrinology and Metabolism, 2020;31(6):410–421).
• Receptor balance tuned differently from tirzepatide. Kailera describes ribupatide as designed with modified potency at the GLP-1 and GIP receptors relative to the leading approved dual agonist; this is a company description, and no peer-reviewed head-to-head receptor pharmacology has been published.
• Extended exposure across the weekly interval. In the Chinese first-in-human study the multiple-dose half-life was seven to eight days, and in a Kailera single-dose study of 1 to 3 mg at one Australian site, exposure was similar in Asian and non-Asian participants once adjusted for body weight (He et al., Diabetes, Obesity and Metabolism, 2026; Klickstein et al., ADA Scientific Sessions 2026, abstract 2648-P). The developers argue that a half-life of seven to eight days, against roughly five days for tirzepatide, maintains receptor engagement through the end of each dosing week.
• Dose-dependent glucose lowering and weight loss from the first weeks. Fasting plasma glucose fell dose-dependently after single and repeated doses in healthy volunteers, and after four weekly doses mean weight change ranged from −6.7% to −9.6% across ribupatide groups versus −1.4% with placebo (He et al., Diabetes, Obesity and Metabolism, 2026).

Research status

Phase 1 (NCT05152277). The first-in-human trial randomized 90 healthy Chinese adults to single ascending doses of 0.1 to 8.1 mg or to four once-weekly doses of 0.9, 2.7 or 5.4 mg (the 5.4 mg arm titrated through 2.7 and 4.0 mg) or placebo; 87 completed. All treatment-emergent adverse events were mild or moderate and there were no serious adverse events. The report, which also contains the preclinical pharmacology, was published online September 20, 2026 (He et al., Diabetes, Obesity and Metabolism, 2026; doi 10.1111/dom.71218) and is, as of November 2026, the only PubMed-indexed primary publication on the molecule. A Kailera single-ascending-dose study at one Australian site gave 49 adults of non-Asian and Asian descent a single untitrated dose of 1, 2 or 3 mg or placebo; most adverse events were mild, none led to discontinuation, and decreased appetite (69%), nausea (62%) and vomiting (36%) were the most common events on active drug (Klickstein et al., ADA Scientific Sessions 2026, abstract 2648-P).

Phase 2 in obesity (HRS9531-201, NCT05881837). A 24-week randomized, double-blind, placebo-controlled trial in 249 Chinese adults with a BMI of 28 to 40 kg/m² tested once-weekly 1, 3, 4.5 and 6 mg. Least-squares mean weight loss from baseline reached 16.8% in the 6 mg group versus 0.1% with placebo, with reductions in blood pressure, glucose and triglycerides; nausea, diarrhea, decreased appetite and vomiting were the most frequent adverse events, mainly during dose escalation (ADA 2024 abstract 1861-LB, Diabetes, 2024;73, Supplement 1). In a 28-week extension, weight loss reached 17.97% at week 32 before all participants switched to active drug, and every-two-week dosing held weight stable through week 52 (ADA 2025 abstract 853-P, Diabetes, 2025;74, Supplement 1). The full trial has not appeared in a peer-reviewed journal.

Phase 2 high-dose cohort (HRS9531-203, NCT06054698). A separate 36-week study randomized 61 adults 4:1 to an 8 mg maintenance dose or placebo. Kailera reports mean weight loss of 23.6% at week 36 under the efficacy estimand versus 1.7% for placebo, with no plateau at week 36. This is the cohort behind the frequently quoted “23% weight loss” figure; it had about 49 participants on active drug, and the data exist only in company presentations.

Phase 2 in type 2 diabetes (HRS9531-202, NCT05966272). In 199 Chinese adults with type 2 diabetes inadequately controlled by lifestyle or metformin (HbA1c 7.5% to 10.5%), once-weekly 1, 2, 3 and 4.5 mg lowered HbA1c by about 2.1 to 2.7 percentage points at week 20 versus 0.3 with placebo, with the effect maintained at week 32 and weight loss of up to 8.9% at the top dose; no clinically significant or severe hypoglycemia was reported (ADA Scientific Sessions 2025, abstract 126-OR). These data remain in abstract form.

Phase 3 in obesity (HRS9531-301, NCT06396429). The pivotal Chinese trial randomized 567 adults without diabetes (mean baseline weight 93 kg) 1:1:1:1 to once-weekly 2, 4 or 6 mg or placebo for 48 weeks. All three doses were superior to placebo on the co-primary and key secondary endpoints. Hengrui reported mean weight loss of 19.2% in the 6 mg group, with 44.4% of that group losing at least 20% of baseline weight; the treatment-policy figure presented at ObesityWeek 2025 was about 17.7%, with no plateau at 48 weeks in the 4 and 6 mg arms. Gastrointestinal events (diarrhea, nausea, decreased appetite and vomiting) were the most common adverse events and rose with dose, and the company described tolerability as consistent with other GLP-1-based drugs (Hengrui, September 3, 2025; topline announced July 2025). The trial has not yet been published in a peer-reviewed journal.

Phase 3 in type 2 diabetes. HRS9531-302 (PRIME-1, NCT06650007), a placebo-controlled trial in 218 adults on diet and exercise alone at 40 Chinese centers, reached primary completion in January 2026 and reported a mean HbA1c reduction of 2.67 percentage points at week 36 in the 4 mg group. HRS9531-303 (PRIME-2, NCT06649344), an open-label trial of 884 adults on metformin with or without an SGLT2 inhibitor at 107 centers, compared 2 and 4 mg with semaglutide 1 mg once weekly: week 36 HbA1c reductions were 2.78 (4 mg), 2.34 (2 mg) and 2.29 (semaglutide) percentage points under the efficacy estimand, both doses met non-inferiority and the 4 mg dose was superior (Hengrui, September 10, 2026). Neither trial has been published in a peer-reviewed journal. A third trial in 300 adults on basal insulin (HRS9531-305, NCT07060456) is recruiting.

Other Chinese trials. A 32-week phase 2 trial in women with obesity and polycystic ovary syndrome, which Hengrui’s announcement calls polyendocrine metabolic ovarian syndrome (HRS9531-207, NCT06595797; 144 planned participants), was presented at EASD 2026; a separate single-center investigator trial in 45 women with PCOS reported 21.4% mean weight loss at 28 weeks with 4 mg versus 9.0% with placebo (ADA 2026 abstract 1815-P). A 26-week phase 2 trial of the oral tablet in 166 adults with obesity (HRS9531-T-201, NCT06841445) produced 6.7%, 11.9% and 11.4% mean weight loss at 10, 25 and 50 mg once daily versus 2.1% for placebo under the treatment-policy estimand (ADA 2026 abstract 2816-LB). Phase 3 trials are running in obstructive sleep apnea with obesity (NCT06974851, NCT06994650), head-to-head against semaglutide in obesity (HRS9531-308, NCT07285902, 572 participants) and with the oral tablet in chronic weight management (HRS9531-T-301, NCT07670884, 675 participants), and a cardiovascular outcomes trial in about 9,260 adults with atherosclerotic cardiovascular disease began in May 2026 with primary completion projected for 2031 (HRS9531-310, NCT07551492). Phase 2 trials in heart failure with preserved ejection fraction (NCT06391710, 203 participants, no longer recruiting) and, alongside Hengrui’s triple agonist HRS-4729, in metabolic dysfunction-associated steatohepatitis (NCT07660848) are ongoing.

Chinese regulatory filings. Hengrui announced on September 3, 2025 that the National Medical Products Administration had accepted its marketing application for ribupatide injection for long-term weight management in adults, and on September 10, 2026 that a second application for glycemic control in adults with type 2 diabetes had been accepted. Hengrui’s third-quarter review of October 28, 2026 still lists both applications as accepted and under review, and no approval for either indication had been announced as of November 2026.

Global program (Kailera). Three phase 3 trials under the KaiNETIC name test once-weekly doses up to 10 mg over 76 weeks against placebo at sites in the United States, Europe, Australia, New Zealand and Argentina: KaiNETIC-1 in 2,530 adults with obesity, or overweight with a comorbidity, without diabetes (NCT07284875, first participants randomized December 2025); KaiNETIC-2 in 1,270 adults with obesity or overweight and type 2 diabetes (NCT07284901, started January 2026); and KaiNETIC-3 in 1,270 adults with a BMI of 35 kg/m² or higher, which includes a semaglutide arm (NCT07284979). Kailera announced on September 30, 2026 that enrollment across the program was complete; primary completion is scheduled for early 2028. A United States phase 2b trial of doses up to 20 mg in 264 adults with a BMI of 35 or higher over 48 weeks (NCT07458269) began in March 2026 and is no longer recruiting, with primary completion projected for mid-2027. No application for approval has been filed with the FDA or the European Medicines Agency.

Common dosage forms

• Investigational subcutaneous injection. Supplied only to clinical-trial sites. Chinese trials have used single-dose and multi-dose pen injectors, whose bioequivalence was tested in a dedicated study (NCT06792955); the presentation that would be marketed in China has not been described publicly.
• Investigational oral tablet. Studied in Chinese phase 2 trials; a second-generation tablet is in relative-bioavailability testing (NCT07150962).
• No approved presentation. No prescription product exists in any country as of November 2026.

Key considerations

• Regulatory status. The Investigational status reflects an active phase 3 program with no marketing approval in any country. Two Chinese marketing applications (weight management, September 2025; type 2 diabetes, September 2026) were under NMPA review as of November 2026.
• Evidence gaps. Every efficacy trial so far was run by the developer in Chinese adults, and the phase 2 and phase 3 obesity and diabetes results exist only as conference abstracts and press releases. The 8 and 10 mg doses now in global phase 3 have not completed a long placebo-controlled trial, there is no completed cardiovascular outcomes trial or peer-reviewed comparison with tirzepatide or semaglutide, and participants in the Chinese phase 3 were lighter on average than those in Western registration trials.
• Safety signals. Adverse events track the incretin class, with gastrointestinal effects rising with dose in every trial. Trials to date were too small and too short to characterize pancreatitis, gallbladder disease, retinopathy progression, thyroid C-cell risk or lean-mass loss, and no tolerability advantage from the GIP balance has been tested head to head against approved agents.
• Naming. HRS9531, HRS-9531, KAI-9531 and ribupatide all denote the same injectable peptide, and “HRS9531 tablet,” “KAI-9531-T” and “oral ribupatide” denote the tablet formulation of the same molecule. It should not be confused with Hengrui’s other incretin programs, HRS-7535 (an oral small-molecule GLP-1 receptor agonist), HRS-4729 (a GLP-1/GIP/glucagon triple agonist) and HRS-1596 (a once-weekly oral GLP-1/GIP dual agonist).