HTD1801 in Combination with Metformin for Type 2 Diabetes

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.).