Author information

• ¹Pinnacle Clinical Research, San Antonio, Texas, USA. sharrison@pinnacleresearch.com.
• ²CINME, Buenos Aires, Argentina.
• ³Alliance for Multispecialty Research, The University of Tennessee Medical Center, Knoxville, TN, USA.
• ⁴City Outpatient Clinic #117, St. Petersburg, Russia.
• ⁵Centro Medico Viamonte, Buenos Aires, Argentina.
• ⁶Centre for Human Drug Research, Leiden, the Netherlands.
• ⁷Chia-Yi Christian Hospital, Chiayi City, Taiwan.
• ⁸Carmel Medical Center, Haifa, Israel.
• ⁹Pennington Biomedical Research Center, Baton Rouge, LA, USA.
• ¹⁰Siriraj Hospital, Bangkok, Thailand.
• ¹¹National Cheng Kung University Hospital, Tainan City, Taiwan.
• ¹²Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
• ¹³Washington University School of Medicine, St. Louis, MO, USA.
• ¹⁴Sheba Medical Center, Ramat Gan, Israel.
• ¹⁵Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
• ¹⁶Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
• ¹⁷Novartis Institutes for BioMedical Research, Basel, Switzerland.
• ¹⁸Novartis Institutes for BioMedical Research, Pudong Shanghai, China.
• ¹⁹Altasciences Algorithme Pharma, Quebec, Canada.

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.