title: Variation in inflammatory markers and glycemic parameters after 12 months of exenatide plus metformin treatment compared with metformin alone: a randomized placebo-controlled trial.
abstract: OBJECTIVE
  To evaluate the effects of exenatide on some inflammatory markers and to quantify the effect of exenatide on β-cell function.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Seven hospitals in Italy.
  
  
  METHODS
  A total of 174 white treatment-naive adults with type 2 diabetes and a glycated hemoglobin (HbA(1c)) level higher than 7.5%.
  
  
  METHODS
  After an open-label run-in period of 8 ± 2 months with metformin, patients were randomized to take exenatide (5 μg twice/day for the first 4 weeks, 10 μg twice/day thereafter) or a placebo volume equivalent for 12 months.
  
  
  RESULTS
  Body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index, homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin (FPPr), proinsulin-to-fasting plasma insulin ratio (Pr:FPI ratio), C-peptide, glucagon, vaspin, chemerin, and resistin were evaluated at baseline, at randomization, and at 3, 6, 9, and 12 months. Patients also underwent a combined euglycemic, hyperinsulinemic, and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. HbA(1c) was significantly improved with exenatide plus metformin compared with placebo plus metformin. Exenatide plus metformin was also significantly more effective than placebo plus metformin in increasing HOMA-β C-peptide, and all measures of β-cell function after the euglycemic hyperinsulinemic and hyperglycemic clamp. We observed that exenatide plus metformin also reduced resistin compared with placebo plus metformin. No variations in vaspin and chemerin were noted in group-to-group comparisons. We observed a significant correlation between M value increase, an index of insulin sensitivity, and a decrease in inflammatory parameters in the exenatide plus metformin group.
  
  
  CONCLUSIONS
  The combination of exenatide plus metformin was more effective than metformin alone in improving glycemic control, β-cell function, and inflammatory parameters.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. giuseppe.derosa@unipv.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
authors.forename: Ivano G
authors.initials: IG
authors.lastname: Franzetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Querci
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.forename: Leonardina
authors.initials: L
authors.lastname: Ciccarelli
authors.forename: Mario N
authors.initials: MN
authors.lastname: Piccinni
authors.forename: Elena
authors.initials: E
authors.lastname: Fogari
authors.forename: Pamela
authors.initials: P
authors.lastname: Maffioli
mesh_terms: D000368:Aged; D001120:Arginine; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D020740:Chimerin Proteins / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004032:Diet; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D000077270:Exenatide; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D052243:Resistin / Q000097:blood; D012307:Risk Factors; D015843:Serpins / Q000097:blood; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D020740:Chimerin Proteins; D007004:Hypoglycemic Agents; D010455:Peptides; D052243:Resistin; C507339:SERPINA12 protein, human; D015843:Serpins; D014688:Venoms; D008687:Metformin; D001120:Arginine; D000077270:Exenatide
keywords: chemerin; exenatide; glycemic control; inflammation; metformin; resistin; vaspin