title: A randomized clinical trial evaluating the safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) treatment generally requires multiple antihyperglycemic agents. When diet, exercise, and treatment with sulfonylurea and metformin do not achieve glycemic goals, several options are available. The present study evaluated the efficacy and tolerability of sitagliptin 100 mg/day added to therapy with sulfonylurea and metformin.
  
  
  METHODS
  Patients with HbA1c ≥7.5% and ≤10.5% while on a sulfonylurea and metformin were randomized 1: 1 to sitagliptin 100 mg/day or placebo for 24 weeks. At Week 24, patients in the placebo group switched to pioglitazone 30 mg/day and both groups continued treatment for another 30 weeks.
  
  
  RESULTS
  Of 427 patients randomized, 339 (79.4%) completed the study. At Week 24, significantly greater (P < 0.001) mean reductions from baseline were seen in the sitagliptin versus placebo group for HbA1c (-0.84% vs -0.16%, respectively), 2-h post-meal glucose (-2.0 vs -0.2 mmol/L, respectively) and fasting plasma glucose (-0.7 vs 0.3 mmol/L, respectively). At Week 54, improvements in glycemic control continued. At Week 24, the incidence of adverse events (AEs) was numerically greater with sitagliptin than placebo, primarily because of a higher incidence of hypoglycemia. At Week 54, the incidence of AEs was similar in both groups, primarily because of a higher incidence of hypoglycemia and edema in the placebo/pioglitazone group after Week 24. The only meaningful change in body weight was an increase in the placebo/pioglitazone group at Week 54.
  
  
  CONCLUSIONS
  In this study, sitagliptin 100 mg/day was generally well tolerated and provided improvement in glycemic control when added to the combination of sulfonylurea and metformin in patients with T2DM.
authors.affiliation: Illawarra Shoalhaven Local Health District, Wollongong, New South Wales, Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Moses
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Round
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shentu
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Golm
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: O'neill
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Gantz
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Engel
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kaufman
authors.affiliation: Merck & Co., Inc, Kenilworth, New Jersey, USA.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016037:Single-Blind Method; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds
keywords: combination therapy; dipeptidyl peptidase-4; incretins; 二肽基肽酶; 联合治疗; 肠促胰素。