Efficacy and safety of HRS-7535, a novel oral small-molecule glucagon-like peptide-1 receptor agonist, in participants with type 2 diabetes mellitus inadequately controlled by metformin and sodium-glucose co-transporter 2 inhibitors: a multicentre, randomised, double-blind, placebo-controlled, parallel-group Phase II trial
- Design
- Randomized trial · 155 participants · Biomarker outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all 155 participants had type 2 diabetes inadequately controlled on metformin and SGLT2 inhibitors; eligibility allowed BMI 20.0-35.0 kg/m2 and ages 18-75.
- Could weight loss explain it?
- Not applicableThe primary outcome is HbA1c change itself; weight change (-2.4% vs -0.7%) was a secondary outcome and no mediation analysis was reported.
- Study tier
- Study tier 3LOW: a 155-person Phase II randomised double-blind trial to week 16 whose primary endpoint is a glycaemic biomarker.
- Assessment
- Version 4 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
This randomised, double-blind trial gave 155 Chinese adults with type 2 diabetes, already on metformin and an SGLT2 inhibitor, the experimental oral GLP-1 drug HRS-7535 (30 mg or 60 mg) or placebo once daily. At week 16, HbA1c fell by 1.5% and 1.8% with the two doses versus 0.4% with placebo, and body weight fell by 2.4% at 60 mg versus 0.7% with placebo. Side effects were mostly mild to moderate and gastrointestinal, with no severe hypoglycaemia; the drug maker funded and co-designed the trial, and some authors are its employees.
01Findings
What the study reported
- Drugs
- Hrs-7535
- Dose
- 30 mg or 60 mg once daily
- Comparator
- placebo (on background metformin and SGLT2 inhibitor therapy)
- Route
- oral
- Treatment duration
- to week 16
- Primary outcome
- change in HbA1c from baseline to week 16
- Effect
- HbA1c change at week 16: -16 mmol/mol (-1.5%) with 30 mg and -20 mmol/mol (-1.8%) with 60 mg versus -4 mmol/mol (-0.4%) with placebo (p<0.0001 for both doses); HbA1c <53 mmol/mol reached by 51.0%, 66.0% and 9.8%; body weight -2.4% (60 mg) vs -0.7% (placebo)
- 95% confidence interval
- Change from baseline in each group: 30 mg 95% CI -19, -14 mmol/mol (-1.7, -1.3%); 60 mg 95% CI -22, -17 mmol/mol (-2.0, -1.6%); placebo 95% CI -7, -2 mmol/mol (-0.6, -0.2%)
- P value
- p<0.0001 for both HRS-7535 doses vs placebo
- Follow-up
- to week 16
- Adverse events
- Most TEAEs mild to moderate, gastrointestinal events most common; no severe hypoglycaemia; the only TEAE leading to discontinuation was in the placebo group
- Limitations
- A Phase II trial of 155 Chinese participants to week 16 with a glycaemic biomarker primary endpoint, sponsored and co-designed by the manufacturer; it cannot show long-term or clinical outcomes.
Who was studied
- Age range
- 18-75 years (eligibility)
- Age min
- 18
- Bmi min
- 20
- Obesity status
- mixed (BMI 20.0-35.0 kg/m2 eligible; obesity not required)
- Diabetes status
- type 2 diabetes required
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- type 2 diabetes inadequately controlled on metformin and SGLT2 inhibitors
- Sample size
- 155
- Inclusion exclusion
- aged 18-75 years, type 2 diabetes, HbA1c 58-97 mmol/mol (7.5-11.0%), BMI 20.0-35.0 kg/m2, stable metformin plus SGLT2 inhibitor for ≥8 weeks
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 155
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo (on background metformin and SGLT2 inhibitor therapy)
- Follow up duration
- to week 16
- Outcome type
- biomarker
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: Change from baseline in each group: 30 mg 95% CI -19, -14 mmol/mol (-1.7, -1.3%); 60 mg 95% CI -22, -17 mmol/mol (-2.0, -1.6%); placebo 95% CI -7, -2 mmol/mol (-0.6, -0.2%)
- Risk of bias
- not assessed
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Jiangsu Hengrui Pharmaceuticals
- Industry funded
- Yes
- Manufacturer
- Jiangsu Hengrui Pharmaceuticals (named as trial sponsor)
- Sponsor role
- Sponsor co-designed the trial and took part in data collection, analysis, interpretation, writing and the decision to submit; medical writing support came from a sponsor employee.
- Author conflicts
- Some authors report consulting and speaker fees from Jiangsu Hengrui Pharmaceuticals, and others are its employees.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Jiangsu Hengrui Pharmaceuticals
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[AIMS/HYPOTHESIS] This study aimed to evaluate the efficacy and safety of HRS-7535, an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1RA), in Chinese participants with type 2 diabetes mellitus inadequately managed by metformin and sodium-glucose co-transporter 2 inhibitors (SGLT2i). [METHODS] This multicentre, randomised, double-blind, placebo-controlled, Phase II study included participants aged 18-75 years with type 2 diabetes, HbA1c 58-97 mmol/mol (7.5-11.0%) and BMI 20.0-35.0 kg/m2 and on stable-dose metformin and sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy for ≥8 weeks prior to screening. Participants were assigned in a 1:1:1 ratio to receive HRS-7535 30 mg, HRS-7535 60 mg or visually matching placebo tablets once daily using a stratified block randomisation method, with treatment assignments concealed until study completion. The primary endpoint was the change in HbA1c from baseline to week 16. Secondary efficacy outcomes included the proportions of participants achieving HbA1c targets of <53 mmol/mol (7.0%) and ≤48 mmol/mol (6.5%), and changes from baseline in fasting body weight to week 16. [RESULTS] A total of 155 participants with a mean baseline HbA1c of 69 mmol/mol (8.5%) were randomly assigned to HRS-7535 30 mg (n=51), HRS-7535 60 mg (n=53) or placebo (n=51). At week 16, the least‑squares mean differences in HbA1c from baseline for the HRS-7535 30 mg, HRS-7535 60 mg and placebo groups were -16 mmol/mol (95% CI -19, -14) (-1.5% [95% CI -1.7, -1.3]), -20 mmol/mol (95% CI -22, -17) (-1.8% [95% CI -2.0, -1.6]) and -4 mmol/mol (95% CI -7, -2) (-0.4% [95% CI -0.6, -0.2]), respectively (p<0.0001 for both HRS-7535 doses vs placebo). The proportions of participants achieving HbA1c <53 mmol/mol (7.0%) were 51.0% in the HRS‑7535 30 mg group, 66.0% in the HRS‑7535 60 mg group, and 9.8% in the placebo group; the corresponding proportions for HbA1c ≤48 mmol/mol (6.5%) were 35.3%, 37.7% and 3.9%, respectively. Body weight loss was -2.4% in the HRS-7535 60 mg group vs -0.7% in the placebo group. Most treatment-emergent adverse events (TEAEs) were mild to moderate, and gastrointestinal adverse events were the most common. No severe hypoglycaemia was reported. The only TEAE that led to treatment discontinuation occurred in the placebo group. [CONCLUSIONS/INTERPRETATION] Treatment with HRS-7535 resulted in significant improvements in glycaemic management in participants with type 2 diabetes, and the drug exhibited a favourable safety profile. To address a significant clinical data void, this research focused on the addition of HRS‑7535 to the background regimen of metformin and SGLT2i for glycaemic management in participants with type 2 diabetes. Trial registration ClinicalTrials.gov NCT06393348. Funding This study was funded by Jiangsu Hengrui Pharmaceuticals.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Oct 18, 2026 | 42875600 first ingestion |