Combination Therapy Potential of HTD1801 (Berberine Ursodeoxycholate) in MASLD/MASH and Cardiovascular–Kidney–Metabolic Disease: A Narrative Review

Background/Objectives: The cardiovascular–kidney–metabolic (CKM) continuum is characterized by the close interrelatedness of metabolic, hepatic, cardiovascular, and renal disease, making multidomain therapies particularly relevant to MASLD/MASH. HTD1801, an investigational ionic therapeutic, combines berberine’s metabolic effects with the hepatoprotective effects of ursodeoxycholic acid (UDCA), making it a potential multidomain therapy within this setting. This review had two related goals: first, to synthesize the mechanistic and clinical evidence for HTD1801 itself; and second, to evaluate the rationale and available evidence for extending this complementary-action approach through combination with other therapies relevant to MASLD/MASH and CKM disease.

Methods

PubMed/MEDLINE, ClinicalTrials.gov, conference abstracts, and selected regulatory or sponsor sources were reviewed through 9 August 2026. Six CKM-relevant therapeutic classes were selected for their human evidence of multidomain benefit: metformin, GLP-1 receptor agonists, statins, SGLT2 inhibitors, PPAR agonists, and resmetirom. Studies of both HTD1801 and its individual components, berberine and UDCA, were included. A systematic review or meta-analysis was not feasible due to the limited and heterogeneous evidence base, instead necessitatinganarrative review.