Two large-scale clinical trials conducted in China have brought new hope for people living with type 2 diabetes mellitus (T2DM). HighTide Therapeutics, a biopharmaceutical company, announced that its drug candidate HTD1801, a combination of berberine and ursodeoxycholate, successfully met its key goals in Phase 3 trials—showing it can significantly lower blood sugar levels and improve related health markers in diabetic patients.

These results come from SYMPHONY 1 and SYMPHONY 2, two studies involving nearly 1,000 adult participants in total. The trials tested HTD1801 both as a standalone treatment and as an add-on to the commonly used drug metformin.

Both SYMPHONY 1 and SYMPHONY 2 were rigorously designed as randomised, double-blind, placebo-controlled trials—widely recognised as the gold standard in clinical research. In each study, participants were randomly assigned to receive either HTD1801 or a placebo, with neither the patients nor the researchers aware of which treatment was being administered, ensuring unbiased results.

SYMPHONY 1 enrolled 407 patients whose type 2 diabetes remained uncontrolled despite lifestyle modifications such as diet and exercise. In contrast, SYMPHONY 2 involved a larger group of 549 patients who were already on metformin, the standard first-line therapy, yet continued to face challenges in managing their blood glucose levels. By targeting two distinct yet clinically relevant patient populations, the trials aimed to comprehensively assess the effectiveness and safety of HTD1801 across different stages of diabetes management.

In both groups, patients taking HTD1801 showed a greater drop in HbA1c levels—the key marker used to measure long-term blood glucose. The average decrease was about 1.2–1.3%, compared to much smaller changes in the placebo groups. For patients with more severe diabetes (those with HbA1c levels ≥ 8.5%), the drop was even more substantial: up to 1.6%.

The drug also helped more people reach the target HbA1c of less than 7%, which is generally considered a sign of well-managed diabetes.

HTD1801 appears to offer a more comprehensive approach to managing diabetes and its related complications. While its primary effect is improving blood sugar control—both fasting and post-meal levels—it also positively impacts other critical health markers. By lowering LDL and non-HDL cholesterol, HTD1801 addresses the lipid abnormalities commonly seen in diabetes, thereby reducing cardiovascular risk. Furthermore, the reduction in inflammation markers such as GGT and hs-CRP highlights its potential to combat the chronic inflammation that often underlies both liver and heart complications in diabetic patients. Taken together, these benefits suggest that HTD1801 is not just a glucose-lowering agent but a multi-targeted therapy capable of addressing the interconnected network of metabolic, cardiovascular, and inflammatory issues in diabetes management.

HTD1801 is a novel therapeutic compound derived from two well-known bioactive agents: berberine, a plant-based alkaloid long used in traditional medicine, and ursodeoxycholate, a bile acid with established metabolic benefits. By combining these two components, HTD1801 harnesses a dual mechanism of action that targets the underlying complexities of type 2 diabetes mellitus (T2DM).

First, it activates AMP-activated protein kinase (AMPK), a key regulator of cellular energy balance. Through activating AMPK, HTD1801 improves the body's ability to handle glucose and fat metabolism, which helps with a main problem in type 2 diabetes—metabolic issues. Second, it inhibits the NLRP3 inflammasome, a critical component of the innate immune system that, when overactivated, contributes to chronic low-grade inflammation—another major driver of insulin resistance and disease progression.

This unique dual-action approach positions HTD1801 as a promising candidate in the treatment of T2DM, offering a synergistic strategy that addresses both metabolic imbalance and inflammation—two interlinked pillars of this complex disease.

The drug was generally well-tolerated. The most common side effects were gastrointestinal issues, such as mild stomach upset. Less than 2% of participants stopped treatment due to side effects, and no cases of severe low blood sugar (hypoglycaemia) were reported.

Dr Linong Ji, a leading diabetes expert and principal investigator of the trials, called the results “encouraging” and emphasised the importance of developing therapies that go beyond just lowering glucose. “Most current drugs focus on single mechanisms. HTD1801 offers a broader approach by also addressing inflammation and lipid metabolism,” he said.

HighTide now plans to submit a New Drug Application (NDA) to China’s drug regulatory body later this year. The company is also running an open-label extension study and preparing for a head-to-head comparison with dapagliflozin, a widely used diabetes drug, to further test HTD1801’s effectiveness.

Type 2 diabetes remains one of the most serious public health problems globally. According to the International Diabetes Federation, 537 million adults had diabetes in 2021, and this number could reach 783 million by 2045. About 90% of these cases are T2DM. China has the highest number of patients, with 141 million people living with the disease in 2021—a figure expected to rise to 174 million in two decades.

The need for innovative, multi-targeted treatments is time-sensitive. If HTD1801 continues to show positive outcomes, it may become an important part of the solution—not just for China, but globally.