Effect of Canagliflozin on liver steatosis in obese non diabetic patients with non-alcoholicfatty liver disease: A double blind randomized controlled trial

Abstract

Objective: To demonstrate whether treatment with canagliflozin had an effect on liver steatosis in obese non-diabetic patients with NAFLD compared with the control group

Methods: 82 nondiabetic patients with BMI 25-35 kg/m2 underwent 24 weeks of double blind randomized controlled trial with combined canagliflozin 100 mg daily with diet-lifestyle modification or placebo with diet-lifestyle modification (500 calories restriction and moderate intensity aerobic exercise). Primary outcome was the change in Controlled attenuation parameter (CAP) representing hepatic steatosis. Liver stiffness measurement (LSM) representing liver stiffness/fibrosis and other secondary outcomes including changes in body weight, fasting plasma glucose, lipid profile, liver function test and FIB-4 index were also evaluated.

Results: At week 24, the Controlled attenuation parameter (CAP) in the canagliflozin group showed a decreasing trend compared with the control group (-13.8 +/- 40.6 db/m vs -0.6 +/- 42.9 db/m, P = 0.168). Significant weight loss was achieved in the canagliflozin group compared with the control group (-1.97 +/- 2.14 kg vs -0.14 +/- 2.57 kg, P = 0.001). A prespecified subgroup analysis in patients with impaired fasting plasma glucose and in those with hepatitis demonstrated significant reduction in CAP (-40.00 +/- 30.7 vs 16.36 +/- 42.60, P = 0.004 and -34.75 +/- 40.84 vs 14.86 +/- 38.36, P = 0.031, respectively).

Conclusion: Treatment with Canagliflozin resulted in a significant weight reduction and may improve hepatic steatosis in obese non-diabetic patients with NAFLD especially in those with impaired fasting plasma glucose or hepatitis.