Safety and metabolic effects of HTD1801 in type 2 diabetes and MASLD: a phase Ib randomized trial

HTD1801 is a novel compound composed of equal parts berberine (BBR) and ursodeoxycholic acid (UDCA). It functions as a gut–liver metabolic modulator with a unique mechanism of action that may offer therapeutic benefits for patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). A total of 48 patients were enrolled in this study. Thirty-six treatment-naïve patients were randomized to receive HTD1801 at doses of 500 mg, 750 mg, or 1000 mg, or placebo, administered twice daily for 28 days. An additional 12 patients on stable metformin therapy were randomized (3:1) to receive either HTD1801 1000 mg or placebo. HTD1801 was generally well tolerated, with most adverse events classified as mild to moderate in severity. No serious adverse events were reported. Berberine exhibited saturation kinetics, whereas UDCA demonstrated linear pharmacokinetics. Accumulation was low to moderate (range: 0.9673 to 2.6659). Compared to placebo, HTD1801 improved glucose and lipid metabolism and reduced liver enzyme levels. A dose-dependent effect was observed, with metabolic improvements increasing with higher administered doses. In the metformin group, HTD1801 (1000 mg) resulted in greater reductions in fasting glucose (mean absolute decrease: −1.271 vs. +0.423 mmol/L), 2-h postprandial glucose (-4.167 vs. +0.290 mmol/L), LDL-C (-0.623 vs. +0.290 mmol/L), total cholesterol (-1.090 vs. +0.023 mmol/L), and GGT (-9.28 vs. -4.43). HTD1801 was safe and demonstrated potential metabolic benefits in patients with T2DM and MASLD. Further investigation is warranted. Retrospectively registered, ChiCTR2500110932 (date: 22nd Oct. 2025), https://www.chictr.org.cn .