HTD1801 is not a hypoglycemic or weight-loss agent in the traditional sense. It is a novel ionic salt composed of berberine (BBR) and ursodeoxycholic acid (UDCA), with its scientific core lying in an innovative dual mechanism of action.

On the one hand, by activating AMP-activated protein kinase (AMPK), HTD1801 ameliorates multiple metabolic abnormalities including glucose and lipid dysregulation at the level of energy metabolism. On the other hand, it precisely inhibits the activation of the NLRP3 inflammasome, alleviating the state of chronic low-grade inflammation from the source. The latter is a key hub for initiating inflammatory responses in the body and is closely associated with insulin resistance, atherosclerosis, renal fibrosis and other pathological processes.

The solid foundation of HTD1801’s "one drug, multiple efficacies" profile has been demonstrated in the completed Phase III clinical trials for type 2 diabetes mellitus (T2DM), including the SYMPHONY 1 and SYMPHONY 2 studies (as monotherapy or in combination with metformin).

Beyond its core hypoglycemic efficacy of reducing glycated hemoglobin (HbA1c) by a significant 1.3%, HTD1801 concurrently induces marked reductions in lipid parameters closely linked to cardiovascular risk—such as low-density lipoprotein cholesterol (LDL-C)—and achieves a significant amelioration of systemic inflammation.

In addition, a striking weight-loss effect of HTD1801 has been observed in clinical studies: in T2DM patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH), treatment with HTD1801 led to a 3.5 kg reduction in body weight from baseline after 18 weeks; in the hyperinsulinemic subgroup, the weight loss even reached an impressive 8 kg.

Preclinical study results further indicate that the weight benefits conferred by HTD1801 are predominantly attributable to a reduction in fat mass.

These synergistic therapeutic benefits reveal HTD1801’s great potential to deliver cardimetabolic benefits to patients.

The latest data presented at the 2025 American Society of Nephrology (ASN) Annual Meeting has elevated the potential clinical value of HTD1801 to a new level: renal protection.

A pooled analysis of Phase III trial data showed that, in the subgroup of T2DM patients with mild renal insufficiency at baseline (estimated glomerular filtration rate [eGFR] 60–90 mL/min/1.73m²), HTD1801 treatment significantly improved the trajectory of eGFR changes compared with placebo, with the annualized eGFR slope increased by a significant 9.81 mL/min/1.73m²/year versus the placebo group (P=0.0106).

This means HTD1801 can not only slow the progression of renal function decline, but also hold the potential to reverse partial early-stage renal impairment. This finding is particularly significant against the backdrop of the high incidence of diabetic kidney disease and the substantial unmet medical needs in current clinical treatments.

Data of HTD1801 from T2DM studies, Source: CVCT Poster

At the 2025 Global Congress on Cardiovascular Clinical Translational Research (CVCT), the data of HTD1801 further reinforced its cardiovascular protective potential. In addition to improving the lipid profile and inflammatory status, analyses demonstrated that HTD1801 significantly reduced the 10-year risk of coronary heart disease calculated by the UK Prospective Diabetes Study (UKPDS) risk model.

This effect is highly consistent with the drug’s theoretical mechanisms—activating AMPK to improve vascular endothelial function and inhibiting NLRP3 to slow the progression of atherosclerosis—providing a coherent scientific explanation for its cardiorenal benefits. Patients are no longer merely regarded as "diabetic patients" or "chronic kidney disease patients", but as a whole with a cluster of interrelated disorders.

And this is the next ambition of HTD1801: to become a backbone therapy for cardio-renal-metabolic (CKM) systemic disorders.

Previously, diabetes, cardiovascular disease, and chronic kidney disease were regarded as independent conditions. However, a wealth of medical evidence in recent years has revealed that they share common pathological underpinnings including insulin resistance, chronic inflammation, and metabolic dysfunction, and they mutually exacerbate one another to form a vicious cycle. In response, the American Heart Association officially proposed the concept of cardio-renal-metabolic (CKM) systemic disorder in 2023, emphasizing the need for a comprehensive intervention strategy.

CKM systemic disorder affects over 1 billion people worldwide, imposing an enormous disease burden. Patients with such conditions often require concurrent management of multiple disorders, leading to complex treatment regimens, heavy medication burden, poor clinical adherence, and a high risk of drug-drug interactions.

This phenomenon of multimorbidity is highly prevalent: nearly 90% of adults in the United States fall within the CKM disease spectrum, while more than half of chronic kidney disease patients in China have comorbid overweight/obesity, with an equally high proportion of comorbid cardiovascular disease.

Agents represented by SGLT2 inhibitors (e.g., dapagliflozin) and GLP-1 receptor agonists (e.g., semaglutide) have become clinical cornerstones due to their well-established cardiorenal protective effects. Nevertheless, existing therapies focus primarily on metabolic regulation, with limited direct intervention on chronic inflammation—a core pathological link—and some are associated with limitations such as genitourinary tract infections and gastrointestinal adverse reactions.

At the same time, the research and development of novel drugs targeting inflammatory pathways has emerged as a hot spot in fields such as cardiovascular protection and metabolic therapy. Amid this competitive landscape, HTD1801 demonstrates unique value through its dual mechanism of AMPK activation + NLRP3 inhibition, strengthening the anti-inflammatory pathway on the basis of metabolic regulation.

To validate its clinical value, VeruShengTai Pharmaceutical has launched the Phase III HARMONY study, a direct head-to-head trial against dapagliflozin—a first-line agent with annual sales exceeding $7 billion.

This study aims to evaluate the efficacy and safety of HTD1801 versus dapagliflozin in adult patients with type 2 diabetes mellitus (T2DM) with inadequate glycemic control despite metformin treatment. The results showed that the trial met its primary endpoint, and HTD1801 outperformed dapagliflozin in improving a number of key cardimetabolic parameters.

Specifically, after 24 weeks of treatment, the HTD1801 group achieved a 1.12% reduction in glycated hemoglobin (HbA1c), superior to the 0.93% reduction in the dapagliflozin group (P<0.001), with a higher proportion of patients reaching the glycemic control target. Notably, HTD1801 exhibited comprehensive regulatory capacity for concomitant reduction of glucose and lipids: it was significantly superior to the dapagliflozin control group in reducing low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein(a)—a cardiovascular risk factor—and a lower proportion of patients in the HTD1801 group required additional statin therapy.

Professor Ji Linong, Principal Investigator of this clinical trial, Former Vice President of the International Diabetes Federation (IDF), Director of the Peking University Diabetes Center, and Director of the Department of Endocrinology and Metabolism at Peking University People’s Hospital, stated: "This suggests that HTD1801 may have greater potential to ameliorate atherosclerotic cardiovascular disease."

Based on these positive data, VeruShengTai has initiated the New Drug Application (NDA) process for HTD1801 for the indication of T2DM. Prior to this, the drug has been granted two Fast Track designations and one Orphan Drug designation by the U.S. Food and Drug Administration (FDA).

Notably, in a university-industry-research collaboration with the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, research on HTD1801 for diabetic kidney disease (CKD with T2DM) is ongoing. Furthermore, VeruShengTai is simultaneously conducting research on the drug in the directions of neuroprotection, anti-tumor activity, and anti-aging effects.

HTD1801 Investigational Indications, Source: Official Website

Against the backdrop where GLP-1 receptor agonists have ignited the weight loss market and SGLT2 inhibitors plus MRAs have solidified their positions in the field of cardiorenal protection, HTD1801, leveraging its unique and complementary dual mechanism of action, has blazed a new trail that ranges from the comprehensive amelioration of blood glucose, body weight and inflammation to definitive cardiorenal protection.

The standout performance of HTD1801 at two top-tier academic conferences in 2025 has sounded the clarion call for its next phase of development. Looking ahead, HTD1801 is poised to serve either as a first-line foundational therapy for patients with early-stage CKM syndrome, delivering holistic risk factor management, or as a combination therapy with SGLT2 inhibitors or GLP-1 receptor agonists to provide dual protection of metabolic regulation and enhanced anti-inflammation for patients in the progressive stage of the disease, addressing more in-depth clinical needs.

This innovative "one drug, multiple efficacies" therapy is advancing steadily in line with the scientific logic of "managing different diseases with the same treatment", and is expected to carve out a niche in the future landscape of comprehensive management for cardio-renal-metabolic systemic disorders.