Berberine Ursodeoxycholate Reduces A1c in Type 2 Diabetes

TOPLINE:

Berberine ursodeoxycholate (HTD1801) showed potential as a treatment option for patients with type 2 diabetes (T2D), with significant reductions in A1c and fasting plasma glucose levels. The treatment was well tolerated, with mild to moderate adverse effects observed.

METHODOLOGY:

• Antidiabetic medications targeting metabolic risk factors along with inducing glycemic control are in demand. HTD1801 is a novel gut-liver anti-inflammatory metabolic modulator that may help manage T2D.
• Researchers conducted a 12-week phase 2 randomized clinical trial at 14 sites in China (March 2022 to January 2023) to evaluate the safety and efficacy of HTD1801 in 113 patients with T2D (mean age, 54.3 years; 36.3% women), which was inadequately controlled with exercise and diet.
• Those with a T2D diagnosis, a history of ≥ 8 weeks of diet and exercise, fasting plasma glucose levels < 250.5 mg/dL, and A1c levels between 7.0% and 11.0% were included.
• Patients were randomly assigned to receive placebo (n = 38), 500 mg of HTD1801 twice daily (n = 37), or 1000 mg of HTD1801 twice daily (n = 38).
• The primary outcome was the change in A1c levels from baseline to week 12. Follow-up was conducted every 4 weeks, with A1c levels measured at baseline and weeks 8 and 12. The secondary outcomes included changes in glycemic and hepatic parameters and safety from baseline to week 12.

TAKEAWAY:

• A dose-dependent reduction in A1c levels was observed after 12 weeks in the 500-mg group (least-squares mean difference, −0.4%; P = .04) and the 1000-mg group (least-squares mean difference, −0.7%; P < .001) compared with the placebo group. At week 12, 55.9% patients in the 1000-mg group vs 15.2% patients in the placebo group achieved A1c levels < 7.0%.
• The mean fasting plasma glucose levels decreased by 13.0 mg/dL in the 500-mg group and by 18.4 mg/dL in the 1000-mg group as opposed to an increase of 0.3 mg/dL in the placebo group.
• HTD1801 treatment led to reductions in non–high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels as well as liver enzyme levels.
• The treatment was well tolerated, with mild to moderate adverse events reported and no significant weight change observed over the 12-week period.

IN PRACTICE:

“These findings support HTD1801 as a well-tolerated oral treatment option that could be used alone or in combination with other available therapies for T2D,” the authors wrote.

“By incorporating novel natural derivatives like HTD1801 into our therapeutic armamentarium, we can address patient preferences and potentially improve adherence — critical factors in achieving meaningful metabolic outcomes for individuals living with type 2 diabetes,” the author of an invited commentary wrote.

SOURCE:

The study was led by Linong Ji, MD, Peking University People’s Hospital, Beijing, China, and was published online in JAMA Network Open.

LIMITATIONS:

The study duration was limited to 12 weeks, which did not allow the long-term effects of HTD1801 to be fully captured. Additionally, the study included an ethnically homogeneous population, unlike previous studies, potentially limiting the generalizability of the findings to other ethnic groups.

DISCLOSURES:

This study was supported by Shenzhen HighTide Biopharmaceutical Ltd, which was involved in the design and conduct of the study. One author reported receiving consulting or lecture fees from various pharmaceutical companies and being a director at Shanghai Benemae Pharmaceutical Corp, outside the submitted work. Three authors reported having stock options in Shenzhen HighTide Biopharmaceutical Ltd, outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.