Nonalcoholic fatty liver disease (NAFLD) is common in T2D patients and increases the risk of NASH and cirrhosis. In a Phase 2 trial, TZP significantly reduced HbA1c and body weight at 26 weeks (≥ 37% achieved 10% weight loss at 2 highest doses). Patients with T2D were randomly assigned (1:1:1:1:1:1) to receive either once-weekly sc TZP (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Because of the overlap of T2D and NAFLD populations, we measured several NASH related biomarkers to explore whether TZP may have potential efficacy in NASH. These included: ALT, AST, Keratin-18 M30 fragment (K-18, apoptosis marker; Peviva), Pro-C3 (fibrosis marker, a fragment of the NH2-terminal propeptide of type III procollagen; Nordic Bioscience), and adiponectin (adipokine that protects liver from inflammation and fibrosis; Pacific Biomarkers). Results (Table) were analyzed in a modified intent-to-treat population using a mixed model for repeated measures. Significant (p<0.05) decreases from baseline with TZP occurred in ALT (all doses), AST (1, 5, 15 mg), K-18 (5, 10, 15 mg) and Pro-C3 (15 mg); decreases were significant for TZP vs. placebo in K-18 (10 mg) and Pro-C3 (15 mg), and for TZP vs. dulaglutide in ALT (10, 15 mg). Increases in adiponectin with TZP were significant compared to placebo for 10 and 15 mg. Further evaluation of TZP in patients with NASH is warranted.
M.L. Hartman: Employee; Self; Eli Lilly and Company. A. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck & Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate. R. Loomba: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc. J.M. Wilson: Employee; Self; Eli Lilly and Company. R. Bray: Employee; Self; Eli Lilly and Company. A. Nikooienejad: Research Support; Self; Eli Lilly and Company. K.L. Duffin: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Pfizer Inc. D.A. Robins: Employee; Self; Eli Lilly and Company. A. Haupt: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Lilly Diabetes.
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