Study Explores Effectiveness of HTD1801 in Type 2 Diabetes

New study findings published by investigators in JAMA Network Open demonstrate that berberine ursodeoxycholate (HTD1801), an oral gut-liver anti-inflammatory metabolic modulator, could be effective for the treatment of type 2 diabetes (T2D).¹

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As one of the most common metabolic disorders worldwide, T2D has an estimated prevalence of 10.5% globally and 11.2% in China, which is marked as the largest number of patients with T2D globally.¹ T2D occurs when the body is unable to use insulin correctly, causing sugar to build up in the blood. With time, T2D could harm the eyes, kidneys, nerves, and heart due to poor insulin response by taking in less sugar. In some cases, individuals live with T2D for years before receiving a diagnosis, as symptoms often present slowly. Symptoms include increased thirst, urination, and hunger; weight loss; tiredness; blurred vision; slow-healing sores; frequent infections; numbness or tingling in the hands or feet; and areas of darkened skin.²

Additionally, with excess nutrition, hyperglycemia and hyperlipidemia worsen insulin resistance and ongoing inflammation. T2D frequently occurs alongside other metabolic problems such as hypertension or metabolic dysfunction-associated steatotic liver disease (MASLD), which intensify T2D and increase the risk of death and heart-related issues.¹

There is currently no cure for T2D; however, losing weight, eating well, and exercising could help manage blood sugar. Diabetes medicines or insulin therapy are often used when diet and exercise are not enough to improve disease management.²

Despite the availability of various diabetes medications, T2D control in China is inadequate, with less than half of patients reaching a hemoglobin A_1c (HbA_1c) level less than 7%. Therefore, there is a strong need for new diabetes drugs that manage multiple metabolic problems, not just blood sugar.¹

HTD1801 could offer further treatment for T2D as a new oral drug combining berberine and ursodeoxycholic acid to fight metabolic and liver diseases. It works by activating adenosine monophosphate (AMP) kinase and inhibiting inflammation, improving glucose and fat use. Its unique structure enhances its effects compared to the individual components.¹

Researchers conducted a phase 2 double-blind, placebo-controlled, 12-week randomized clinical trial at 14 sites in China between March 2022 and January 2023, evaluating the safety and efficacy of HTD1801 among individuals with T2D. Participants were included if they underwent 8 or more weeks of diet and exercise, had a HbA_1c level of 7.0% to 10.5%, and had a fasting plasma glucose (FPG) level less than 250.5 mg/dL.¹

A total of 113 individuals with T2D were included and were randomized 1:1:1 to placebo (38), HTD1801 500 mg twice daily (37), and HTD1801 1000 mg twice daily (38). Individuals included in the study were an average age of 54.3 years and had a baseline HbA_1c level of 8.2%.¹

After 12 weeks, HTD1801 significantly reduced HbA_1c levels compared to placebo, with a reduction of -0.4% in the 500 mg group and -0.7% in the 1000 mg group. Further results demonstrated that FPG also improved, with reductions of -13.0 mg/dL in the 500 mg group and -18.4 mg/dL in the 1000 mg group. The 1000 mg group also showed improvements in lipids and liver injury markers.¹

Additional findings demonstrated that HTD1801 was well-tolerated, with 97.3% of patients completing the study, and 52.2% experiencing mild adverse events. However, one serious adverse event, retinal hemorrhage, was deemed unlikely related to the treatment.¹

The findings displayed that treatment with HTD1801 resulted in significant reductions in the HbA_1c level and improved key cardiometabolic and liver parameters. However, the study authors noted that the findings are being confirmed in ongoing phase 3 studies.¹

REFERENCES

1. Berberine Ursodeoxycholate for the Treatment of Type 2 Diabetes. JAMA Network Open. News release. Published March 3, 2025. Accessed March 18, 2025. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2830820?resultClick=1

2. Mayo Clinic. Type 2 Diabetes. February 27, 2025. Accessed March 18, 2025. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193