title: Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes.
abstract: OBJECTIVE
  To assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (≥1500 mg/day) and pioglitazone (≥30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A1c [HbA1c] ≥7.5% and ≤11%).
  
  
  METHODS
  This placebo-controlled, double-blind study included 313 patients, mean baseline HbA1c=8.7%, who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks.
  
  
  RESULTS
  The addition of sitagliptin led to significant (P<.001) mean changes from baseline relative to placebo in HbA1c (-0.7%), fasting plasma glucose (-1.0 mmol/L), and 2-h post-meal glucose (-2.2 mmol/L). In patients with baseline HbA1c ≥9.0%, mean changes from baseline in HbA1c were -1.6% and -0.8% for the sitagliptin and placebo groups, respectively (between-group difference -0.8%; P<.001). The incidences of reported adverse events were generally similar between the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%] and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P=.786). Two patients, both in the placebo group, experienced an episode of hypoglycemia that required non-medical assistance.
  
  
  CONCLUSIONS
  In this 26-week study, addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated.
authors.affiliation: Tulane University Medical Center, New Orleans, LA, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Morgan
authors.forename: Yue
authors.initials: Y
authors.lastname: Shentu
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Golm
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Goldstein
authors.forename: Helmut
authors.initials: H
authors.lastname: Steinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D059012:Lost to Follow-Up; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists; D010352:Patient Dropouts; D000077205:Pioglitazone; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D047495:PPAR gamma; D000077205:Pioglitazone; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; C517652:hemoglobin A1c protein, human