Novel Berberine Drug Cut HbA1c in Type 2 Diabetes

 I started using berberine years ago because this: Berberine reduces triglycerides levels and systolic blood pressure.^123,124

Don't follow me, I'm not medically trained, is your doctor trained in this?

Novel Berberine Drug Cut HbA1c in Type 2 Diabetes

Higher-dose group also reported liver-related improvements

by Kristen Monaco, Senior Staff Writer, MedPage Today March 3, 2025

Key Takeaways

• Two strengths of berberine ursodeoxycholate improved HbA1c compared with placebo in a phase II trial.
• The higher-dose group also had improvements in other metabolic and liver markers.
• The treatment appeared to be safe and well-tolerated.

An investigational compound incorporating an herbal-based supplement improved blood glucose in adults with inadequately controlled type 2 diabetes in a Chinese phase II randomized clinical trial.

By week 12, HbA1c significantly improved among participants on twice-daily berberine ursodeoxycholate at 500 mg (-0.4%, 95% CI -0.79% to -0.03%, P=0.04) or 1,000 mg (-0.7%, 95% CI -1.10% to -0.35%, P<0.001) compared with placebo, Linong Ji, MD, of Peking University People's Hospital in Beijing, and colleagues wrote in JAMA Network Open.

More participants in the higher-dose group than placebo achieved an HbA1c under 7% (55.9% vs 15.2%) or under 6.5% (29.4% vs 6.1%). Significant drops in fasting plasma glucose levels were also reported in the 500 and 1,000 mg groups (-13.0 mg/dL and -18.4 mg/dL).

Though most participants had normal liver markers at baseline, the high-dose group had significant reductions in aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase levels from baseline. Other metabolic and inflammatory markers including LDL cholesterol, HDL cholesterol, non-HDL cholesterol, total cholesterol, fasting C-peptide, and HOMA-IR also improved in this group. Body weight didn't significantly change in any group.

Treatment was safe and well-tolerated, and nearly all participants completed the trial. The most common treatment-emergent adverse event was hyperlipidemia, occurring in three patients in each treatment group and in two placebo patients.

Berberine ursodeoxycholate, also known as HTD180, is a first-in-class orally administered gut-liver anti-inflammatory metabolic modulator. The compound "provides a unique dual mechanism of action (adenosine monophosphate [AMP] kinase activation and NLRP3 inflammasome inhibition) compared with the current therapeutic landscape," Ji and co-authors wrote. It represents "a new molecular entity that offers the possibility of combination therapy for chronic metabolic and nonviral liver diseases in a single treatment."

Berberine on its own has long been used in traditional Chinese and ayurvedic medicine and recently shot to popularity in the U.S., being touted on social media as "nature's Ozempic" for its potential metabolic benefits.

"Berberine shares several mechanisms of action with metformin, including activation of AMP-activated protein kinase, inhibition of gluconeogenesis, modulation of gut microbiota, and anti-inflammatory and antioxidant effects. These metabolic benefits may have led to its promotion as an alternative or adjunct to metformin, despite its lack of FDA approval for diabetes treatment," accompanying commentary author Nestoras Mathioudakis, MD, MHS, of Johns Hopkins University School of Medicine in Baltimore, pointed out.

Berberine's poor bioavailability is one of its drawbacks, said Mathioudakis, and "enhancing the absorption of berberine has been a key focus of research." Ji and co-authors said this prompted them to combine berberine with ursodeoxycholic acid, a key regulator of bile acid and inflammatory pathways that has been used to treat hepatobiliary disorders and cholestatic conditions, to boost pharmacological effects.

Putting berberine ursodeoxycholate's glucose-lowering effects into perspective, Mathioudakis said that equivalent doses of metformin tend to yield similar, but slightly more potent, results.

"[M]etformin at doses of 500 mg twice daily can reduce the HbA1c level by 1.0% to 1.5%, while 1,000 mg twice daily may achieve reductions of 1.5% to 2.0% over similar time frames [to the trial]," he wrote. But its glucose-lowering effects "align with other FDA approved antihyperglycemic medications," including SGLT2 inhibitors and DPP-4 inhibitors.

For certain patients, berberine ursodeoxycholate could "offer advantages over metformin," Mathioudakis added, which may include fewer adverse events, potential liver benefits, and a possible option for people who want natural alternatives. "By incorporating novel natural derivatives ... 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," he said.

The 14-site trial was conducted in China between March 2022 and January 2023 and enrolled 113 participants with type 2 diabetes. Average age was 54.3 years and 63.7% were male. At baseline, HbA1c was 8.2%, body mass index (BMI) was 25.5, and fasting plasma glucose was 160.7 mg/dL. Prior to the study, all participants underwent 8 or more weeks of diet and exercise and then were randomly assigned 1:1:1 in groups balanced for baseline disease severity.

The short 12-week follow-up and exclusively Han Chinese patient population were some of the study's limitations.

Ji's group said berberine ursodeoxycholate is being studied in more trials for type 2 diabetes and metabolic dysfunction-association steatohepatitis(MASH). The FDA previously granted it fast-track designation for both MASH and primary sclerosing cholangitis (PSC), and orphan drug designation for PSC.

• 

  Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was funded by Shenzhen HighTide Biopharmaceutical.

Ji reported relationships with Shenzhen HighTide Biopharmaceutical, Eli Lilly, Novo Nordisk, Merck, Bayer, Sanofi-Aventis, Roche, MSD, Metronics, AstraZeneca, Boehringer Ingelheim, Abbott, Fosun Pharma, Innovent Biologics, Gan & Lee Pharmaceuticals, Sinocare, Sibionics, and Shanghai Benemae Pharmaceutical Corp.

Co-authors reported relationships with Shenzhen HighTide Biopharmaceutical.

Mathioudakis reported no disclosures.

Primary Source

JAMA Network Open

Source Reference: opens in a new tab or windowJi L, et al "Berberine ursodeoxycholate for the treatment of type 2 diabetes: a randomized clinical trial" JAMA Netw Open 2025; DOI: 10.1001/jamanetworkopen.2024.62185.

Secondary Source

JAMA Network Open

Source Reference: opens in a new tab or windowMathioudakis N "A berberine derivative for treatment of type 2 diabetes" JAMA Netw Open 2025; DOI: 10.1001/jamanetworkopen.2024.62195.