A clinical trial to test the effectiveness of a new, plant-based oral drug to treat type 2 diabetes has produced some promising results. The drug significantly improved blood glucose control and boosted heart and liver health. Larger clinical studies are pending.
Berberine is a naturally occurring alkaloid found in various plants. It has been used for centuries in traditional Chinese medicine (TCM) to treat digestive issues, inflammation, and bacterial infections.
Researchers from Peking University People’s Hospital in China recently conducted a phase 2 clinical trial assessing the safety and effectiveness of a berberine derivative, berberine ursodeoxycholate, to treat type 2 diabetes (T2D).
T2D is the most common form of diabetes, accounting for around 90% of all diabetics. It is caused by insulin resistance, where the body can’t respond fully to the insulin the pancreas produces, so blood glucose rises (hyperglycemia). Adopting a healthy lifestyle is often the first step in treating T2D, with the aim of preventing disease progression and reducing blood glucose to normal or near-normal levels. If that fails, oral antidiabetic medications can be introduced.
Berberine ursodeoxycholate, or HTD1801, has been evaluated in different clinical studies. In 2021, US researchers conducted a phase 2 clinical trial using it to treat non-alcoholic fatty liver disease. The study participants were also type 2 diabetics, which is commonly associated with this kind of liver disease, and almost all of them were taking oral antidiabetic medications, often two or more at the same time. The researchers found that in addition to reducing liver fat content, HTD1801 significantly improved blood glucose control. Glycated hemoglobin or HbA1c is a blood test that measures average blood glucose levels over the preceding two to three months. It’s the key marker for blood glucose (glycemic) control.
Based on the results of the 2021 study, the present clinical trial aimed to evaluate HTD1801’s effectiveness in patients with T2D alone, whose blood glucose levels had been inadequately controlled with diet and exercise. Trial investigators recruited 113 patients with T2D – the mean age was around 54 – and randomized them to one of three 12-week treatment groups: placebo; 500 mg of HTD1801 twice daily; or 1,000 mg of HTD1801 twice daily.
The study’s primary endpoint was a significant improvement in blood glucose control, as reflected in a reduced HbA1c. At baseline, patients’ HbA1c levels were between 7% and 11% (mean 8.2%), where a normal, non-diabetic HbA1c is below 5.7%. After 12 weeks, the primary endpoint had been achieved. Significant dose-dependent reductions in HbA1c were seen in both HDT1801 treatment groups compared to the placebo group. For the placebo group, the reduction in HbA1c was 0.3%. Those taking 500 mg twice a day saw a reduction of 0.4%, which just pushed it into the realm of statistical significance. However, those on the higher dose of 1,000 mg twice daily had a reduction in HbA1c of 0.7%, a clinically meaningful reduction.
In real-world terms, many of the 34 patients randomized to take 1,000 mg of HTD1801 twice daily achieved target HbA1c levels. At week 12, 55.9% had an HbA1c of less than 7%, and for 29.4% it was less than 6.5%. Consistent with these reductions in HbA1c, the researchers also observed that HTD1801 produced dose-dependent improvements in glucose metabolism and insulin resistance compared to placebo. HTD1801 also reduced low-density lipoprotein cholesterol (LDL-C, the ‘bad’ type) levels and markers of inflammation and cardiovascular risk. None of the patients experienced significant weight gain.
The researchers deemed HTD1801 treatment “generally safe and well tolerated.” Adverse events were seen in all three groups, including the placebo, but affected 71.1% of patients in the 1,000-mg group, compared to 46% and 39.5% of patients in the 500-mg and placebo groups, respectively. Four patients experienced severe adverse events; all the other episodes were mild to moderate in severity, including one mild hypoglycemic event that the researchers determined was not caused by HTD1801. No clinically significant abnormalities were seen in lab tests, vital signs, physical exams, or electrocardiograms (EEGs) in any group.
“In this phase 2 placebo-controlled randomized clinical trial, treatment with HTD1801 (500 mg twice daily and 1,000 mg twice daily) resulted in significant reductions in HbA1c levels compared with placebo at 12 weeks,” said the researchers. “Additional improvements were observed in glycemic, cardiometabolic, and liver-related parameters, demonstrating the comprehensive benefit of HTD1801 for the treatment of T2D and its comorbidities. 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 trial was funded by Shenzhen HighTide Biopharmaceutical Ltd, the manufacturers of HTD1801.
The study was published in the journal JAMA Network Open.
