Hengrui’s HRS‑7535, an oral GLP‑1 agonist, delivered up to 11.1% weight loss and 1.68% HbA1c reduction in Phase 3 obesity and diabetes trials. China NDAs planned; global Phase 2 ongoing.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Hengrui Pharma and Kailera has reported positive topline results from two Phase 3 clinical trials evaluating its investigational oral GLP-1 receptor agonist HRS-7535 in adults with obesity or overweight and type 2 diabetes (T2D) in China. The studies met their primary endpoints, demonstrating clinically meaningful weight reduction and glycemic control while maintaining a favorable liver safety profile.
The obesity study, HARBOR-1 (NCT06904105), showed that once-daily HRS-7535 produced mean weight loss of up to 10.9% at Week 44 and 11.1% at Week 50 using the efficacy estimand. In the diabetes trial, OUTSTAND-2 (NCT06589765), the highest dose lowered HbA1c by 1.68%, outperforming dapagliflozin while meeting the study’s primary non-inferiority objective across all evaluated doses.
Oral GLP-1 therapy expands metabolic treatment options
HRS-7535 is an investigational oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist developed by Hengrui Pharma and licensed outside Greater China to Kailera as KAI-7535. Unlike injectable GLP-1 therapies, the once-daily oral candidate could offer a more convenient treatment option for patients with obesity and type 2 diabetes if approved.
More than 2,000 participants have received HRS-7535 across clinical studies in China. Kailera is also evaluating the molecule in a global Phase 2 obesity trial, with results anticipated in 2027.
Phase 3 obesity trial showed consistent and durable weight reduction
The randomized, double-blind, placebo-controlled HARBOR-1 trial enrolled 556 adults with obesity or overweight. Participants received HRS-7535 at 120 mg, 180 mg, or placebo for 44 weeks.
Using the efficacy estimand, participants receiving the 120 mg and 180 mg doses achieved 9.5% and 10.9% mean weight loss from baseline at Week 44, compared with 2.5% for placebo. An ad hoc analysis at Week 50 showed sustained weight reductions of 9.5% and 11.1%, respectively.
The treatment also improved HbA1c, systolic blood pressure, and lipid parameters. Clinically meaningful weight-loss thresholds were frequently achieved, with up to 68.2% of participants losing at least 5% of body weight, 46.6% losing at least 10%, and 26.0% losing at least 15%.
Most treatment-emergent adverse events were mild to moderate gastrointestinal events, primarily nausea, vomiting, and diarrhea. Treatment discontinuation due to adverse events remained low at 4.1% and 3.1% for the two HRS-7535 dose groups. Investigators reported no liver safety signals, consistent with previous studies.
Diabetes trial outperformed dapagliflozin at the highest dose
The OUTSTAND-2 Phase 3 trial enrolled 810 adults with inadequately controlled type 2 diabetes receiving metformin. Participants were randomized to HRS-7535 at 30 mg, 60 mg, 90 mg, or dapagliflozin 10 mg.
At Week 32, HbA1c reductions reached 1.58%, 1.50%, and 1.68% across the three HRS-7535 dose groups compared with 1.28% for dapagliflozin. The 90 mg dose demonstrated superior HbA1c reduction versus the comparator while all dose groups met the predefined non-inferiority endpoint.
HRS-7535 also improved body weight, systolic blood pressure, lipid profiles, and urinary albumin-to-creatinine ratio. No Grade 3 hypoglycemic events occurred, and liver safety findings remained consistent with earlier clinical experience.
Regulatory plans move toward China filings
Hengrui plans to present detailed findings from both Phase 3 studies at upcoming scientific meetings and intends to submit New Drug Applications (NDAs) in China for HRS-7535 in both obesity and type 2 diabetes. The company is advancing the oral GLP-1 candidate as part of a broader effort to expand treatment options in metabolic diseases while Kailera continues global clinical development outside Greater China.
What This Means for Patients
If approved, HRS-7535 could offer people with obesity or type 2 diabetes a once-daily oral alternative to injectable GLP-1 medicines. In these Phase 3 studies, the treatment produced clinically meaningful weight loss and improved blood sugar control while also showing benefits for blood pressure and cholesterol. The most common side effects were mild to moderate gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, and no liver safety concerns were identified. HRS-7535 remains investigational and is not yet approved for clinical use.
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About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.