title: Effects of exenatide and metformin in combination on some adipocytokine levels: a comparison with metformin monotherapy.
abstract: The aim of this study was to evaluate the effects of exenatide on levels of serum adipocytokines and on β-cell function. The study was conducted between 2008 and 2012. After a run-in period with metformin, 174 patients with type-2 diabetes were randomly distributed to either a group receiving exenatide at 10 μg twice daily, or a group receiving the placebo, for 12 months. We evaluated body mass index (BMI), blood pressure, glycemic control, lipid profile, fasting plasma insulin (FPI), HOMA-IR, HOMA-β, fasting plasma proinsulin (FPPr), proinsulin : fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, retinol binding protein-4 (RBP-4), visfatin, omentin-1, and microalbuminuria. We used ELISA methods to assess the various parameters. Patients also underwent a combined euglycemic-hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. After 12 months, a combination of exenatide and metformin produced a better decrease in body mass, BMI, glycemic control, FPI, FPPr, FPPr/FPI ratio, HOMA-IR, and glucagon level. Treatment with exenatide + metformin was superior to the placebo + metformin in increasing HOMA-β, C-peptide, and β-cell function. Significant negative correlations were found between M value, an index of insulin sensitivity, and measured adipocytokines. In conclusion, the combination of exenatide + metformin plays a role in improving some adipocytokine levels, and is better than metformin alone. The significant negative correlation between M value and measured adipocytokines is another confirmation of the positive effects linked to the improvement in insulin sensitivity.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Piazzale Camillo Golgi 2, 27100 Pavia, Italy. giuseppe.derosa@unipv.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
authors.forename: Arrigo F G
authors.initials: AF
authors.lastname: Cicero
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: Angela
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Elena
authors.initials: E
authors.lastname: Fogari
authors.forename: Pamela
authors.initials: P
authors.lastname: Maffioli
mesh_terms: D054392:Adipokines / Q000097:blood*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D057194:Intention to Treat Analysis; D007558:Italy; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D054392:Adipokines; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D008055:Lipids; D010455:Peptides; D014688:Venoms; D008687:Metformin; D000077270:Exenatide