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Berberine Ursodeoxycholate for the Treatment of Type 2 Diabetes: A Randomized Clinical Trial.

JAMA network open2025-03-03PubMed
Total: 77.0Innovation: 8Impact: 7Rigor: 8Citation: 7

Summary

In a 12-week, phase 2 double-blind RCT (n=113), HTD1801 reduced HbA1c dose-dependently versus placebo (−0.4% and −0.7% for 500 mg and 1000 mg b.i.d.) and improved fasting glucose, lipids, and liver injury markers (at 1000 mg). The regimen was well tolerated with high completion rates.

Key Findings

  • Dose-dependent HbA1c reductions at 12 weeks vs placebo: −0.4% (500 mg) and −0.7% (1000 mg).
  • FPG improved in both HTD1801 groups; lipid and liver injury markers improved in the 1000 mg group.
  • Safety and tolerability were favorable with a 97.3% completion rate and mostly mild adverse events.

Clinical Implications

HTD1801 may become an oral option for patients with T2D needing concurrent improvements in glycemia, liver injury markers, and lipids pending phase 3 confirmation.

Why It Matters

First-in-class gut–liver anti-inflammatory modulator demonstrating glycemic and extra-glycemic benefits in T2D, aligning with the need for therapies addressing cardiometabolic comorbidities.

Limitations

  • Short duration (12 weeks) and modest sample size; conducted in a single country
  • Not powered for hard cardiometabolic outcomes; longer-term safety/efficacy pending

Future Directions

Phase 3 trials to confirm durability and breadth of benefits, define target populations, and assess effects on NASH/MASH-related endpoints and cardiovascular risk.

Study Information

Study Type
RCT
Research Domain
Treatment
Evidence Level
II - Phase 2 double-blind randomized controlled trial
Study Design
OTHER