title: Fixed-dose combination therapy for type 2 diabetes: sitagliptin plus pioglitazone.
abstract: BACKGROUND
  Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione pioglitazone into a fixed-dose single-tablet combination. The former component acts mainly to increase prandial insulin secretion; the latter improves insulin sensitivity.
  
  
  METHODS
  To date, clinical trials conducted in type 2 diabetes patients have used combinations of sitagliptin (100 mg/day) and pioglitazone (30 - 45 mg/day) as separate tablets. These trials have shown that the combinations offer additive efficacy in reducing blood glucose when given as initial antidiabetic therapy and as add-on therapy when pioglitazone alone fails to maintain glycemic control.
  
  
  RESULTS
  Initial therapy with a combination of sitagliptin (100 mg/day) and pioglitazone (30 mg/day) reduced HbA1c by > 2% starting from a baseline > 9%. Adding sitagliptin (50 - 100 mg/day) to patients inadequately controlled on pioglitazone reduced HbA1c by 0.7 - 1.4% from a baseline of 8 - 8.5%. The combination did not increase the risk of hypoglycemia and produced similar or slightly more weight gain than pioglitazone alone when introduced as initial antidiabetic therapy.
  
  
  CONCLUSIONS
  The combination of sitagliptin and pioglitazone was well tolerated in these trials, and would appear to be suited to a fixed-dose single-tablet combination for once-daily administration.
authors.affiliation: Aston University, Department of Life and Health Sciences, Birmingham, UK. c.j.bailey@aston.ac.uk
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Bailey
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone