title: A randomized, double-blind, comparative therapy evaluating sitagliptin versus glibenclamide in type 2 diabetes patients already treated with pioglitazone and metformin: a 3-year study.
abstract: OBJECTIVE
  This study evaluated if triple oral therapy can be useful in improving glycemic control compared with metformin monotherapy and with a metformin and pioglitazone combination. Furthermore, we also compared a triple metformin+pioglitazone+glibenclamide combination with a metformin+pioglitazone+sitagliptin one.
  
  
  METHODS
  After a 2-year run-in therapy-augmenting phase with metformin and pioglitazone, 453 overweight, type 2 diabetes patients were randomized to 1 year of sitagliptin versus 1 year of glibenclamide to evaluate, as the primary outcome, the variation of β-cell function both in a fasting state and after an euglycemic hyperinsulinemic and hyperglycemic clamp. As secondary outcomes we evaluated glycemic control and insulin resistance.
  
  
  RESULTS
  Both the triple therapy combinations were more effective in reducing glycated hemoglobin compared with metformin monotherapy and with dual therapy metformin+pioglitazone. Fasting plasma insulin level and the homeostasis model assessment insulin resistance index were significantly increased by triple therapy with glibenclamide and decreased by the one with sitagliptin. Although sitagliptin did not change the homeostasis model assessment β-function index, this value was significantly increased by glibenclamide. The fasting plasma proinsulin level was decreased by sitagliptin. Triple therapy with sitagliptin greatly improved β-cell function measures compared with the glibenclamide one and also compared with metformin monotherapy and with the metformin+pioglitazone combination.
  
  
  CONCLUSIONS
  Dual combination therapy is more effective than monotherapy in improving glycemic control. When double therapy is not enough to reach an adequate glycemic control, sitagliptin should be preferred to glibenclamide as the third agent because of its positive effect on β-cells.
authors: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors: Giuseppe
authors: G
authors: Derosa
authors: Arrigo F G
authors: AF
authors: Cicero
authors: Ivano G
authors: IG
authors: Franzetti
authors: Fabrizio
authors: F
authors: Querci
authors: Anna
authors: A
authors: Carbone
authors: Mario N
authors: MN
authors: Piccinni
authors: Angela
authors: A
authors: D'Angelo
authors: Elena
authors: E
authors: Fogari
authors: Pamela
authors: P
authors: Maffioli
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D005905:Glyburide / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D009765:Obesity / Q000097:blood / Q000150:complications; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; C517652:hemoglobin A1c protein, human