Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus

作者：Kenneth Cusi, Beverly Orsak, Fernando Bril, Romina Lomonaco, Joan Hecht, Carolina Ortiz‐Lopez, Fermin O. Tio, Jean Hardies, Celia Darland, Nicolas Musi, Amy Webb, Paola Portillo-Sánchez · 发表于：Annals of Internal Medicine · 年份：2016 · DOI：10.7326/m15-1774 · 被引用次数：1012 · 研究领域：Liver Disease Diagnosis and Treatment、Diabetes, Cardiovascular Risks, and Lipoproteins、Diet and metabolism studies

BACKGROUND: The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone. However, information about its long-term use in this population is limited. OBJECTIVE: To determine the efficacy and safety of long-term pioglitazone treatment in patients with NASH and prediabetes or T2DM. DESIGN: Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT00994682). SETTING: University hospital. PARTICIPANTS: Patients (n = 101) with prediabetes or T2DM and biopsy-proven NASH were recruited from the general population and outpatient clinics. INTERVENTION: All patients were prescribed a hypocaloric diet (500-kcal/d deficit from weight-maintaining caloric intake) and then randomly assigned to pioglitazone, 45 mg/d, or placebo for 18 months, followed by an 18-month open-label phase with pioglitazone treatment. MEASUREMENTS: The primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease activity score in 2 histologic categories without worsening of fibrosis. Secondary outcomes included other histologic outcomes, hepatic triglyceride content measured by magnetic resonance and proton spectroscopy, and metabolic parameters. RESULTS: Among patients randomly assigned to pioglitazone, 58% achieved the primary outcome (treatment difference, 41 percentage points [95% CI, 23 to 59 percentage points]) and 51% had resolution of NASH (treatment differenc...