title: Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function.
abstract: OBJECTIVE
  The effects of sitagliptin and pioglitazone, alone and in combination, on α- and β-cell function were assessed in patients with type 2 diabetes.
  
  
  METHODS
  Following a 6-week diet/exercise period, 211 patients with HbA1c of 6.5-9.0% and fasting plasma glucose of 7.2-14.4 mmol/l were randomized (1 :1 :1 : 1) to sitagliptin, pioglitazone, sitagliptin + pioglitazone or placebo. At baseline and after 12 weeks, patients were given a mixed meal followed by frequent blood sampling for measurements of glucose, insulin, C-peptide and glucagon.
  
  
  RESULTS
  After 12 weeks, 5-h glucose total area under the curve (AUC) decreased in all active treatments versus placebo; reduction with sitagliptin + pioglitazone was greater versus either monotherapy. The 5-h insulin total AUC increased with sitagliptin versus all other treatments and increased with sitagliptin + pioglitazone versus pioglitazone. The 3-h glucagon AUC decreased with sitagliptin versus placebo and decreased with sitagliptin + pioglitazone versus pioglitazone or placebo. Φ(s), a measure of dynamic β-cell responsiveness to above-basal glucose concentrations, increased with either monotherapy versus placebo and increased with sitagliptin + pioglitazone versus either monotherapy. The insulin sensitivity index (ISI), a composite index of insulin sensitivity, improved with pioglitazone and sitagliptin + pioglitazone versus placebo. The disposition index, a measure of the relationship between β-cell function and insulin sensitivity, improved with all active treatments versus placebo.
  
  
  CONCLUSIONS
  Sitagliptin and pioglitazone enhanced β-cell function (increasing postmeal Φ(s)), and sitagliptin improved α-cell function (decreasing postmeal glucagon) after 12 weeks in patients with type 2 diabetes. Through these complementary mechanisms of action, the combination of sitagliptin and pioglitazone reduced postmeal glucose more than either treatment alone.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Alba
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: S E
authors.initials: SE
authors.lastname: Inzucchi
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.forename: M
authors.initials: M
authors.lastname: Mallick
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: E A
authors.initials: EA
authors.lastname: O'Neill
authors.forename: D E
authors.initials: DE
authors.lastname: Williams-Herman
authors.forename: K D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: B J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008875:Middle Aged; D000077205:Pioglitazone; D019518:Postprandial Period / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D005934:Glucagon; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone
keywords: DPP-4; MK-0431; PPARγ agonist; dipeptidyl peptidase-4 inhibitors; incretins