Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study

Stephen A. Harrison, Federico Perez Manghi, William B. Smith, Diana Alpenidze, Diego Aizenberg, Naomi Klarenbeek, Chi Yi Chen, Eli Zuckerman, Eric Ravussin, Phunchai Charatcharoenwitthaya, Pin Nan Cheng, Helena Katchman, Samuel Klein, Ziv Ben-Ari, Anisha E. Mendonza, Yiming Zhang, Miljen Martic, Shenglin Ma, Sheena Kao, Sandra TannerAlok Pachori, Michael K. Badman, Yan Ling He, Chinweike Ukomadu, Eric Sicard

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that may advance to fibrosis and lead to mortality; however, no pharmacotherapy is currently available. We tested the hypothesis that inhibition of both the sodium–glucose cotransporters 1 and 2 with licogliflozin would lead to improvement in NASH. A total of 107 patients with phenotypic or histologic NASH were randomized (1:2:2) to receive oral administration of either placebo (n = 21), licogliflozin 30 mg (n = 43) or 150 mg (n = 43) once daily for 12 weeks. Licogliflozin 150 mg showed a significant 32% (80% confidence interval (CI): 21–43%; P = 0.002) placebo-adjusted reduction in serum alanine aminotransferase after 12 weeks of treatment, the primary endpoint of the study. However, the 30 mg dose of licogliflozin did not meet the primary endpoint (placebo-adjusted reduction 21% (80% CI: 7–32%; P = 0.061)). Diarrhea occurred in 77% (33 of 43), 49% (21 of 43) and 43% (9 of 21) of patients treated with licogliflozin 150 mg, 30 mg and placebo, respectively, which was mostly mild in severity. No other major safety concerns were identified. Treatment with 150 mg licogliflozin led to reductions in serum alanine aminotransferase in patients with NASH. Studies of longer duration and in combination with drugs that have different mechanisms of action are needed to validate these findings and to define a role of licogliflozin as a therapeutic option for NASH. ClinicalTrials.gov identifier: NCT03205150.

Original languageEnglish
Pages (from-to)1432-1438
Number of pages7
JournalNature Medicine
Volume28
Issue number7
DOIs
Publication statusPublished - 2022 Jul

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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