title: Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β antibody, in patients with type 2 diabetes.
abstract: 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-1β antibody, in T2DM patients.
  
  
  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 HbA1c 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.
  
  
  CONCLUSIONS
  Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA1c and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1β holds promise as a convenient adjuvant treatment for T2DM.
authors.affiliation: 1Chorus, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, Indiana, USA j.s.lancas@lilly.com
authors.forename: Joanne
authors.initials: J
authors.lastname: Sloan-Lancaster
authors.forename: Eyas
authors.initials: E
authors.lastname: Abu-Raddad
authors.forename: John
authors.initials: J
authors.lastname: Polzer
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Miller
authors.forename: Joel C
authors.initials: JC
authors.lastname: Scherer
authors.forename: Andrea
authors.initials: A
authors.lastname: De Gaetano
authors.forename: Jolene K
authors.initials: JK
authors.lastname: Berg
authors.forename: William H
authors.initials: WH
authors.lastname: Landschulz
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010919:Placebos
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D010919:Placebos; C586827:LY2189102; C517652:hemoglobin A1c protein, human