berberine ursodeoxycholate (HTD1801) / HighTide Therap - LARVOL DELTA

A Randomized Placebo-Controlled Trial of HTD1801 Monotherapy in Participants With Type 2 Diabetes. (PubMed, Diabetes Care) - "HTD1801 treatment produced sustained improvements in glycemic, cardiometabolic, and inflammatory parameters, supporting further evaluation as a well-tolerated oral therapy for patients with type 2 diabetes."

Journal • Monotherapy • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Negentropy: A Mechanistic Study on the Effect of HTD1801 Versus Placebo on Kidney Function in Patients With Type 2 Diabetes and Chronic Kidney Disease. (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • CST3

Berberine-Ursodeoxycholate - Bringing Traditional Chinese Medicine to Our World. (PubMed, NEJM Evid) - No abstract available

Journal

HTD1801 Attenuates Podocyte Apoptosis and Glomerular Injury: Mechanistic Insights into Renoprotection (ERA 2026) - "By reducing podocyte inflammation/apoptosis and stabilizing glomerular structure, HTD1801 acts as a disease-modifying therapy independent of glycemic control.The convergence of clinical and histological data supports HTD1801 as a potent drug candidate targeting fundamental pathophysiologic processes in patients with CKD or rare renal diseases. Image"

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • ANXA5 • CASP3 • NLRP3 • NPHS1

Enhanced Weight Loss when HTD1801 Is Combined with GLP-1RAs in DIO Mice (ADA 2026) - "HTD1801 enhances weight loss with improved weight loss quality when combined with a GLP-1RA and mitigates body weight and glycemic rebound after GLP-1RA discontinuation."

Preclinical • Metabolic Disorders • Obesity • NLRP3

Long-Term Safety and Efficacy of HTD1801 in Patients with Type 2 Diabetes: Two Phase 3 Open-Label Extensions (ADA 2026) - "In two 24-week, double-blind (DB), placebo-controlled Phase 3 studies, HTD1801, administered as monotherapy (SYMPHONY-1) or as add-on to metformin (SYMPHONY-2), significantly reduced HbA1c versus placebo in patients with type 2 diabetes (T2D). HTD1801 showed sustained cardiovascular-kidney-metabolic benefits and consistent safety through 52 weeks, supporting its potential as a well-tolerated, effective therapy for patients with T2D."

Clinical • P3 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • NLRP3

Harmony: A Head-to-Head Phase 3 Study of HTD1801 vs. Dapagliflozin (ADA 2026) - "The HARMONY study evaluated the efficacy and safety of HTD1801 vs Dapa in patients with T2D. Key entry criteria of this Phase 3 double-blind, active-controlled study: T2D, HbA1c 7.0%-10.5%, FPG ≤250.5 mg/dL, and stable metformin use ≥8 weeks. HTD1801 provided glycemic control comparable to Dapa, with more pronounced and distinctive effects on CV risk factors and therefore may provide a unique treatment option for patients with T2D."

Head-to-Head • P3 data • Metabolic Disorders • NLRP3

HTD1801 in Combination with Metformin for Type 2 Diabetes. (PubMed, NEJM Evid) - P3 | "After 24 weeks, HbA1c reduction was significantly greater among patients with T2D taking metformin and randomly assigned to receive HTD1801 versus placebo. A higher proportion of patients in the HTD1801 group experienced mild to moderate diarrhea compared with the placebo group. (Funded by Shenzhen HighTide Biopharmaceutical; ClinicalTrials.gov number, NCT06353347.)."

Journal • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Safety and metabolic effects of HTD1801 in type 2 diabetes and MASLD: a phase Ib randomized trial. (PubMed, Diabetol Metab Syndr) - P1 | "HTD1801 was safe and demonstrated potential metabolic benefits in patients with T2DM and MASLD. Further investigation is warranted."

Journal • P1 data • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Inhibiting cuproptosis mitigates cholangiocyte inflammation in primary biliary cholangitis (EASL 2026) - "Finally, in the phase 2 clinical trial in PBC patients with inadequate response to standard therapy, berberine ursodeoxycholate demonstrated reduced ALP levels at week-12 (-9.82%; 95%CI: -19.5 ~ -0.11; P=0.048). We report herein an association between cuproptosis and PBC progression. Berberine treatment represents a promising therapeutic strategy for modulating cuproptosis in associated pathologies."

Autoimmune Hepatitis • Fibrosis • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Metabolic Dysfunction-Associated Steatotic Liver Disease • Primary Biliary Cholangitis • DLAT

Negentropy: A Mechanistic Study on the Effect of HTD1801 Versus Placebo on Kidney Function in Patients With Type 2 Diabetes and Chronic Kidney Disease. (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences

New P2 trial • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • CST3

HighTide’s First NDA for Diabetes Drug HTD1801 Accepted by China’s NMPA (TipRanks) - "The NDA follows three multicenter, randomized, double-blind, controlled Phase III trials in which HTD1801 met primary and multiple secondary endpoints and improved glycemic control, lipid metabolism, inflammatory markers, and renal function. These findings position HTD1801 as a potential single therapy addressing multiple facets of the cardiovascular-kidney-metabolic spectrum, which, if successfully brought to market, could offer differentiated value to patients and healthcare systems and support the company’s long-term growth trajectory."

China filing • Type 2 Diabetes Mellitus

Berberine: A Negentropic Modulator for Multi-System Coordination. (PubMed, Int J Mol Sci) - "Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub-axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling."

Journal • Review • Inflammation • Metabolic Disorders • AMPK • NLRP3

SYMPHONY-1: Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=408 | Completed | Sponsor: HighTide Biopharma Pty Ltd | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

HARMONY: Effects of Berberine Ursodeoxycholate (HTD1801) Versus Dapagliflozin in Patients With Type 2 Diabetes Inadequately Controlled With Metformin (clinicaltrials.gov) - P3 | N=367 | Completed | Sponsor: HighTide Biopharma Pty Ltd | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Symphony2: Efficacy and Safety of Berberine Ursodeoxycholate (HTD1801) in Patients With Type 2 Diabetes Inadequately Controlled With Metformin (clinicaltrials.gov) - P3 | N=551 | Completed | Sponsor: HighTide Biopharma Pty Ltd | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Aug 2025

Trial completion • Trial completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Evidence of Kidney Benefit with HTD1801 in Patients with Mild Renal Impairment (KIDNEY WEEK 2025) - "Conclusion These data provide the first clinical evidence that a therapy may benefit patients with CKD by improving the eGFR trajectory and recovering kidney function from the earliest stages of CKD, distinguishing HTD1801from existing therapies. The findings suggest a potential disease-modifying effect, indicating that HTD1801 may improve the eGFR trajectory."

Clinical • Late-breaking abstract • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • NLRP3

A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple Repeated Dose Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HTD1801 in Patients with Type 2 Diabetes Mellitus (ChiCTR) - P1 | N=57 | Completed | Sponsor: The First Hospital of Jilin University; The First Hospital of Jilin University

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

SYMPHONY-2 (HTD1801 as an add-on therapy to Metformin): (TradingView) - "At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.2%) was superior to placebo. HbA1c reductions were sustained in patients who continued receiving HTD1801 (-1.1% at Week 52). Placebo patients who switched to HTD1801 saw a reduction in HbA1c of -1.2% at Week 52, also substantiating the double-blind phase findings."

P3 data • Type 2 Diabetes Mellitus

HighTide plans to submit a new drug application (NDA) for HTD1801 as a treatment for T2DM to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) later this year. (TradingView)

China filing • Type 2 Diabetes Mellitus

SYMPHONY-1 (HTD1801 as monotherapy): (TradingView) - "At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.3%) was superior to placebo. HbA1c reductions were maintained in patients who continued receiving HTD1801 (-1.2% at Week 52). Placebo patients who switched to HTD1801 saw a reduction in HbA1c of -1.3% at Week 52, substantiating the double-blind phase findings."

P3 data • Type 2 Diabetes Mellitus

Berberine: A Bitter Phytochemical With Diversely Sweet Therapeutic Properties. (PubMed, Nutr Rev) - "Indeed, available evidence suggests that further investigations may reveal that berberine ursodeoxycholate offers comparable efficacy to metformin, with fewer side effects. The superior efficacy and safety profile make this agent suitable for patients with type 2 diabetes with kidney and liver complications."

Journal • Cardiovascular • Chronic Kidney Disease • Dental Disorders • Diabetes • Dyslipidemia • Hepatology • Metabolic Disorders • Nephrology • Oncology • Periodontitis • Renal Disease • Type 2 Diabetes Mellitus

Symphony 2: a randomised, placebo-controlled phase 3 study of berberine ursodeoxycholate in patients with type 2 diabetes inadequately controlled with metformin (EASD 2025) - P3 | "Treatment with HTD1801 in patients with T2D and an inadequate response with metformin was safe and generally well tolerated. Furthermore, HTD1801 treatment resulted in significant improvements in glycemic control and key cardiometabolic parameters demonstrating comprehensive benefits in this complex metabolic disease."

Clinical • P3 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus • NLRP3

"Surrogates Without Substance?" Questioning the Evidence for Histologic Improvement With HTD1801. (PubMed, Clin Mol Hepatol) - No abstract available

Journal

Letter to the editor on "HTD1801 demonstrates promising potential for histologic improvements in metabolic dysfunction-associated steatohepatitis in both a preclinical and phase 2 study. ". (PubMed, Clin Mol Hepatol) - No abstract available

Journal • P2 data • Preclinical • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis