HRS-7535 (KAI-7535): The Oral GLP-1 Pill With 11% Weight Loss

HRS-7535 — licensed outside Greater China as KAI-7535 — is a once-daily oral small-molecule GLP-1 receptor agonist from Jiangsu Hengrui Pharmaceuticals and Kailera Therapeutics. In July 2026 it became one of the few pills in its class to report Phase 3 obesity results, with up to 11.1% mean weight loss. It is also the rare candidate whose earlier trials have already cleared peer review in Nature Communications, JAMA Network Open, and eClinicalMedicine — which makes it possible to check the press release against the published record.

Evidence: "Once-daily oral HRS-7535 at doses of 60 mg or higher produced clinically meaningful weight loss and was generally well tolerated." — Gu W, et al. Nature Communications. 2026. DOI: 10.1038/s41467-026-73018-y

What Is HRS-7535?

HRS-7535 is a non-peptide, small-molecule GLP-1 receptor agonist taken as a once-daily tablet. Hengrui developed it in China; in 2024 Kailera Therapeutics acquired rights outside Greater China, where the molecule carries the code KAI-7535. Both names describe the same compound.

The chemistry is the reason it can be a pill at all. Semaglutide, liraglutide, and tirzepatide are peptides — protein fragments that stomach acid and digestive enzymes destroy before absorption. That is why they are injected, and why the peptide-based oral semaglutide tablet needs an absorption enhancer plus strict fasting rules to deliver a usable dose.

A synthesized small molecule sidesteps the problem. It survives digestion without help, needs no cold chain, and scales through conventional tablet manufacturing rather than the constrained peptide supply chain. HRS-7535 shares this design with orforglipron, aleniglipron, and CX11. It is also Hengrui's second obesity asset licensed to Kailera, alongside the injectable dual agonist ribupatide (HRS9531).

How It Works

The drug activates the same receptor as every agent in the class, producing the familiar sequence:

Appetite suppression through hypothalamic GLP-1 signaling, which reduces hunger and quiets food noise
Slowed gastric emptying, prolonging fullness after meals
Glucose-dependent insulin secretion, improving glycemic control without provoking hypoglycemia
Suppressed glucagon release, lowering fasting glucose

The Phase 1 program established that the molecule behaves like a once-daily drug. Pharmacokinetics were roughly dose-proportional, with a half-life of 6.5–8.4 hours after 28 days of dosing, and healthy participants titrated to 120 mg lost a mean of 4.38 kg (6.63%) in a month versus 0.8 kg on placebo.

Evidence: "HRS-7535 exhibited a safety and tolerability profile consistent with other GLP-1RAs and showed PKs suitable for once-daily dosing." — Wu J, et al. Diabetes, Obesity and Metabolism. 2024. DOI: 10.1111/dom.15383

HRS-7535 Phase 3 Results: HARBOR-1

HARBOR-1 (NCT06904105) is the pivotal obesity trial and the source of the July 2026 headlines. It randomized 556 Chinese adults with obesity or overweight in a 2:2:1 ratio to HRS-7535 120 mg, 180 mg, or placebo once daily for 44 weeks. Mean baseline weight was 94.1 kg and mean BMI 34.0 kg/m².

Mean weight reduction (efficacy estimand):

Arm	Week 44	Week 50 (ad hoc)
HRS-7535 120 mg	−9.5%	—
HRS-7535 180 mg	−10.9%	−11.1%
Placebo	−2.5%	—

Responder rates at the higher dose were 68.2% for at least 5% weight loss, 46.6% for at least 10%, and 26.0% for at least 15%. Discontinuation due to adverse events was 4.1% and 3.1% in the two active arms, and investigators reported no liver safety signals — a meaningful detail for a small-molecule class in which hepatic signals have derailed earlier candidates.

A companion Phase 3 in type 2 diabetes, OUTSTAND-2 (NCT06589765), met its primary non-inferiority endpoint against dapagliflozin, with the highest dose lowering HbA1c by 1.68% versus 1.28% for the comparator at week 32.

These are company-reported top-line results. The full efficacy tables, estimand definitions, and adverse-event breakdowns that ultimately determine how a drug is judged have not been published or presented in full. Hengrui has said it will submit New Drug Applications in China for both obesity and type 2 diabetes.

What the Peer-Reviewed Phase 2 Data Show

Unusually for a drug at this stage, three randomized Phase 2 trials of HRS-7535 have already been published, and they anchor the Phase 3 numbers in something more verifiable than a press release.

Obesity

The Phase 2 obesity trial randomized 235 Chinese adults with a BMI of 28.0–40.0 kg/m² across four doses and placebo for 26 weeks.

Dose	LS mean weight change	Placebo-adjusted	P value
30 mg	−2.99%	−0.49%	0.7104
60 mg	−7.09%	−4.60%	0.0006
120 mg	−6.17%	−3.67%	0.0062
180 mg	−9.36%	−6.87%	<0.0001
Placebo	−2.50%	—	—

Two things stand out. The 30 mg dose was indistinguishable from placebo, confirming a genuine threshold below which the drug does nothing useful. And the 120 mg result landed below the 60 mg result — a non-monotonic pattern that, in a trial with roughly 47 participants per arm, most likely reflects sampling noise rather than a real dip in the dose–response curve. The Phase 3 selection of 120 mg and 180 mg suggests the sponsors read it the same way.

Type 2 Diabetes

A separate 16-week Phase 2 trial tested HRS-7535 as an add-on in 194 adults whose diabetes was inadequately controlled on metformin. HbA1c fell by 1.19% to 1.82% across doses versus 0.25% on placebo, and 48.7% to 63.2% of treated patients reached an HbA1c below 7.0%, compared with 15.4% on placebo. Weight reduction in this population was modest — 2.63% at the 90 mg dose — which is expected at diabetes-range doses over 16 weeks.

Evidence: "Because HRS-7535 is a nonpeptide oral GLP-1 RA that does not require fasting administration or injection, it may be a viable treatment option, pending confirmation in phase 3 trials." — Guo L, et al. JAMA Network Open. 2026. DOI: 10.1001/jamanetworkopen.2026.15622

Diabetic Kidney Disease

The SOLID-DKD trial adds an organ-protection dimension that most obesity pills have not yet tested. It randomized 281 patients with diabetic kidney disease — already on intensive therapy, including SGLT2 inhibitors in 64.6% and finerenone in 24.3% — to 30 mg, 90 mg, or placebo for 16 weeks. At the 90 mg dose, albuminuria fell 32% more than placebo, alongside a 1.09% greater HbA1c reduction and 2.95% greater weight loss.

That result matters because it was achieved on top of the two best-established kidney drugs, suggesting an additive mechanism rather than a redundant one. It aligns with the broader signal on GLP-1 medications and kidney health.

How HRS-7535 Compares With Other Oral GLP-1 Pills

Drug	Dose	Weight loss	Duration	Evidence status
HRS-7535	180 mg	−10.9%	44 weeks	Phase 3 top-line (China)
Orforglipron	36 mg	−11.2%	72 weeks	Phase 3, peer-reviewed
CX11 (VCT220)	160 mg	−12.4%	52 weeks	Phase 3 top-line (China)
Semaglutide 2.4 mg (injection)	—	−14.9%	68 weeks	Phase 3, peer-reviewed

Cross-trial comparison is not a substitute for a head-to-head study — these trials differ in population, duration, BMI entry criteria, and estimand — but the pattern is consistent: oral small molecules cluster around 10–12% weight loss, while injectable peptides reach the mid-teens and above.

The comparison HRS-7535 will actually face is against the pills already approaching market. An indirect treatment comparison of the two front-runners found oral semaglutide 25 mg produced 3.2 percentage points more weight loss than orforglipron 36 mg, with markedly fewer discontinuations for gastrointestinal side effects. HRS-7535's 44-week result sits near orforglipron's 72-week result, which is arguably favorable on a per-week basis — and arguably not comparable at all, since weight-loss curves flatten over time.

Tolerability and Safety

Gastrointestinal effects are the defining constraint of this class, and HRS-7535 does not escape them. Across every published trial, nausea, vomiting, and diarrhea were the most common adverse events, predominantly mild to moderate, and concentrated during dose escalation. In the Phase 1 study, nausea and vomiting were the most frequently reported events at every stage.

The reassuring counterweight is that few people stopped. Discontinuation for adverse events was 3.1–4.1% in HARBOR-1 and 1.1–3.2% in SOLID-DKD. Across the published Phase 2 program there were no cases of level 2 or 3 hypoglycemia, no pancreatitis, and no liver enzyme elevations above three times the upper limit of normal.

Two caveats belong alongside those numbers. Every trial to date was conducted in China, so the safety profile in other populations — and at Western baseline BMIs, which run higher than the 34.0 kg/m² mean in HARBOR-1 — remains unestablished. And the detailed adverse-event tables from HARBOR-1 have not been published, so the Phase 3 tolerability picture rests on a summary rather than the data.

What Happens Next

Hengrui plans Chinese NDA submissions for both obesity and type 2 diabetes. Kailera, which holds rights everywhere else, began a Phase 2 trial in adults with obesity or overweight in April 2026 — meaning the global program is roughly a full development cycle behind the Chinese one.

Realistic expectations:

HRS-7535 is not available by prescription anywhere. It is investigational in every market, including China, until an NDA is approved.
A U.S. approval is years away. A Phase 2 that started in 2026 puts pivotal global trials at 2027 or later, followed by 68–72 weeks of treatment, analysis, and review.
The next real milestone is publication. Every HARBOR-1 and OUTSTAND-2 figure above comes from a company announcement. The published Phase 2 record is encouraging precisely because it can be checked.
Anything sold online as "HRS-7535" or "KAI-7535" is not the drug. The same warning applies to compounded semaglutide obtained outside regulated pharmacies.

Key Takeaways

HRS-7535 is a credible entrant rather than a breakthrough. Its Phase 3 obesity trial produced 10.9% mean weight loss at 44 weeks — squarely in the band the oral small-molecule class has established, below injectable peptides, and achieved with low discontinuation and no liver signal.

What distinguishes it is the depth of its published evidence. Three peer-reviewed randomized trials across obesity, type 2 diabetes, and diabetic kidney disease is more than most candidates at this stage can show, and the kidney data hint at a role beyond weight alone.

The open questions are geography and durability: every trial so far has run in China, and no dataset yet extends past a year. For anyone weighing GLP-1 therapy today, the approved options carry years of outcome data — and that decision belongs with your physician.

References

Gu W, Zhang L, Li L, et al. HRS-7535, an oral small-molecule GLP-1 receptor agonist, in Chinese adults with obesity without diabetes: a randomized, double-blind, placebo-controlled phase 2 trial. Nature Communications. 2026;17(1):7867. DOI: 10.1038/s41467-026-73018-y
Guo L, Sun Z, Zhang L, et al. HRS-7535 for Type 2 Diabetes Inadequately Controlled With Metformin: A Randomized Clinical Trial. JAMA Network Open. 2026;9(6):e2615622. DOI: 10.1001/jamanetworkopen.2026.15622
Lv R, Peng L, Xu Y, et al. Efficacy and safety of HRS-7535, an oral small-molecule GLP-1 receptor agonist, in patients with diabetic kidney disease (SOLID-DKD): a randomised, double-blind, placebo-controlled, phase 2 trial. eClinicalMedicine. 2026;97:104045. DOI: 10.1016/j.eclinm.2026.104045
Wu J, Zhou R, Zhang Q, et al. Safety, pharmacokinetics and pharmacodynamics of HRS-7535, a novel oral small molecule glucagon-like peptide-1 receptor agonist, in healthy participants: A phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food effect trial. Diabetes, Obesity and Metabolism. 2024;26(3):901–910. DOI: 10.1111/dom.15383
Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1). New England Journal of Medicine. 2025;393(18):1796–1806. DOI: 10.1056/NEJMoa2511774
Michalak W, Bøg M, Bendixen T, et al. Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. Diabetes, Obesity and Metabolism. 2026;28(8):7247–7256. DOI: 10.1111/dom.70919
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021;384(11):989–1002. DOI: 10.1056/NEJMoa2032183

Note: HARBOR-1 and OUTSTAND-2 Phase 3 figures are drawn from Hengrui Pharma and Kailera Therapeutics top-line announcements and have not yet been published in a peer-reviewed journal. They should be treated as preliminary. All Phase 1 and Phase 2 figures cited above are from the peer-reviewed publications listed.

Last updated: 2026-08-08 Medical review: Dr. James Chen, MD, PhD, FACE