Double-blind, randomized study evaluating the glycemic and antiinflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β Antibody, in patients with type 2 diabetes

OBJECTIVE-Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1β may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to determine the efficacy, safety, and tolerability of LY2189102, a neutralizing IL-1b antibody, in T2DM patients. RESEARCH DESIGN AND METHODS-Phase II, randomized, double-blind, parallel, placebo-controlled study of subcutaneous LY2189102 (0.6, 18, and 180 mg) administered weekly for 12 weeks in T2DM patients on diet and exercise, with or without approved antidiabetic medications. RESULTS-LY2189102 reduced HbA at 12 weeks (adjusted mean differences versus placebo: 20.27, 20.38 and 20.25% for 0.6, 18 and 180 mg doses, respectively), and fasting glucose at multiple time points compared with placebo. LY2189102 also reduced postprandial glycemia, and inflammatory biomarkers, including hs-CRP and IL-6. LY2189102 was generally well tolerated. CONCLUSIONS-Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1? holds promise as a convenient adjuvant treatment for T2DM. © 2013 by the American Diabetes Association.