- 2026-06-23
- NEJM evidence 5(7)
- Linong Ji
- Zhifeng Cheng
- Jianhua Ma
- Dexue Liu
- Xin Zhang
- Xiaolin Dong
- Yang Lin
- Mingming Yang
- Shenglian Gan
- Hanqing Cai
- Xiaomei Wang
- Yan Liu
- Xiaoguang Shi
- Kui Liu
- Leigh MacConell
- Meng Yu
- Liping Liu
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 365
- Population
- patients with T2D, glycated hemoglobin (HbA1c) 7.0% to 10.5%, fasting glucose levels of 250.5 mg/dl or lower, and stable use of metformin for 8 weeks or more
- Methods
- phase 3 double-blind trial; patients were randomly assigned 2:1 to receive either HTD1801 1000 mg orally twice daily (n=365) or placebo (n=184) in addition to their prior metformin treatment
- Blinding
- Double-blind
- Duration
- 24 weeks
- Funding
- Industry-funded
Background
HTD1801 is an anti-inflammatory metabolic modulator being developed to treat type 2 diabetes (T2D). The safety and efficacy of HTD1801 as an add-on to metformin among patients with T2D with inadequate glycemic control despite stable metformin use have not been well evaluated.Methods
This phase 3 double-blind trial included patients with T2D, glycated hemoglobin (HbA1c) 7.0% to 10.5%, fasting glucose levels of 250.5 mg/dl or lower, and stable use of metformin for 8 weeks or more. Patients were randomly assigned 2:1 to receive either HTD1801 1000 mg orally twice daily (n=365) or placebo (n=184) in addition to their prior metformin treatment. The primary end point was change in HbA1c from baseline to week 24. Data on adverse events were collected during this 24-week time frame.Results
The mean HbA1c was 8.6% at baseline and 7.4% at 24 weeks in the HTD1801 group (mean change, -1.2 percentage points; 95% confidence interval [CI], -1.3 to -1.1). The mean HbA1c was 8.5% at baseline and 7.8% at 24 weeks in the placebo group (mean change, -0.7 percentage point; 95% CI, -0.8 to -0.6). The adjusted least-squares mean difference between groups for the change in HbA1c from baseline to week 24 was -0.5 (95% CI, -0.7 to -0.4; P<0.0001). Diarrhea was the most common adverse event (HTD1801, 23.8%; placebo, 1.1%), with three cases in the HTD1801 group graded as severe, and all the other cases being mild to moderate in severity. No patients experienced severe hypoglycemia.Conclusions
After 24 weeks, HbA1c reduction was significantly greater among patients with T2D taking metformin and randomly assigned to receive HTD1801 versus placebo. A higher proportion of patients in the HTD1801 group experienced mild to moderate diarrhea compared with the placebo group. (Funded by Shenzhen HighTide Biopharmaceutical; ClinicalTrials.gov number, NCT06353347.).