Berberine Ursodeoxycholate Shows Promise in Type 2 Diabetes Treatment: JAMA
A phase II clinical trial in China has found that berberine ursodeoxycholate (HTD1801) effectively improved HbA1c levels in adults with inadequately controlled type 2 diabetes (T2D) compared to a placebo. The higher-dose group also showed improvements in metabolic and liver markers. Additionally, the treatment was safe and well-tolerated, highlighting its potential as a promising therapy. The trial findings have been published in the Journal of American Medical Association by Linong Ji and colleagues.
The trial was double-blind, placebo-controlled to assess the safety and efficacy of HTD1801 in adults with T2D. The participants had an HbA1c value between 7.0% and 10.5% and an FPG value less than 250.5 mg/dL. Participants were randomly divided into three groups: placebo (n=38), HTD1801 500 mg twice a day (n=37), and HTD1801 1000 mg twice a day (n=38). The main outcome was the difference in HbA1c from baseline to 12 weeks. The secondary outcomes were differences in glycemic, hepatic, and cardiometabolic parameters. Analysis of results used a mixed-effects model for repeated measures.
Key Findings
• The participants' mean age was 54.3 years and 63.7% were male.
• The mean HbA1c at baseline was 8.2%, BMI was 25.5, and FPG was 160.7 mg/dL.
• At week 12, HbA1c decrease was significant in both groups of HTD1801:
• 500 mg group: -0.4% (95% CI, -0.79% to -0.03%; p=0.04)
• 1000 mg group: -0.7% (95% CI, -1.10% to -0.35%; p<0.001)
FPG improved:
• 500 mg group: -13.0 mg/dL
• 1000 mg group: -18.4 mg/dL
• Lipid profiles and liver injury markers also improved in the 1000 mg group.
• HTD1801 was tolerable, as 97.3% of participants completed the study.
• There were mild adverse effects in 52.2% of subjects, but nobody stopped treatment due to side effects.
• There was a serious adverse event (retinal hemorrhage) in a single patient receiving 500 mg, but this was considered to be unrelated to the treatment.
This phase 2 trial showed that HTD1801 significantly reduces HbA1c and FPG levels, as well as liver and cardiometabolic markers, in T2D patients. The drug was well tolerated, with no significant safety issues. These results indicate that HTD1801 may provide a novel oral treatment for diabetes management beyond glycemic control. More studies are required to validate these advantages in larger populations.
Reference:
Ji L, Ma J, Ma Y, et al. Berberine Ursodeoxycholate for the Treatment of Type 2 Diabetes: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(3):e2462185. doi:10.1001/jamanetworkopen.2024.62185
