Double-Blind, Randomized Study Evaluating the Glycemic and Anti-inflammatory Effects of Subcutaneous LY2189102, a Neutralizing IL-1β Antibody, in PatientsWith Type 2 Diabetes

OBJECTIVEInflammation is associated with pancreatic -cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1 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-1 antibody, in T2DM patients.RESEARCH DESIGN AND METHODSPhase 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.RESULTSLY2189102 reduced HbA(1c) at 12 weeks (adjusted mean differences versus placebo: -0.27, -0.38 and -0.25% 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.CONCLUSIONSWeekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA(1c) and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1 holds promise as a convenient adjuvant treatment for T2DM.