title: Glimepiride strongly enhances the glucose-lowering effect in triple oral antidiabetes therapy with sitagliptin and metformin for Japanese patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  After approval of sitagliptin and >750 mg of metformin in Japan, a triple oral antidiabetes drug (OAD) regimen including sulfonylurea, metformin, and sitagliptin was sometimes described. However, in the real world of clinical practice, the daily dose of sulfonylurea tended to be decreased according to the warning from the Japan Diabetes Society for avoiding hypoglycemia, instead of increasing the dose of metformin for maintaining hemoglobin A1c (HbA1c) levels with this regimen. This study examined the impact of either a small dose of glimepiride or a high dose of metformin on HbA1c in triple OAD therapy with sitagliptin in a 3-month, single-center, open-label, randomized controlled study.
  
  
  METHODS
  Fifty-six type 2 diabetes mellitus patients who had been treated with 50 mg of sitagliptin, ≥ 1,000 mg of metformin, and ≤ 1 mg of glimepiride with an HbA1c level of <7.4% during at least 3 months were enrolled in the study. The patients were randomly assigned to two treatment groups who either received a 50% reduced dose of metformin (n = 27) or discontinued glimepiride (n = 29), while sitagliptin administration continued in both groups. Twenty-six patients from the reduced metformin group and 27 patients from the discontinued glimepiride group completed the study.
  
  
  RESULTS
  Significantly greater changes were observed in HbA1c and glycated albumin levels in patients who discontinued glimepiride than in patients with a 50% reduced metformin dose, during the 2-3-month period than in the 1-3-month period.
  
  
  CONCLUSIONS
  Glimepiride is important for good glycemic control in triple OAD therapy with sitaglitpin and metformin. This regimen may be useful for those patients who do not achieve satisfactory glycemic control with dual combination therapy.
authors.affiliation: Arai Clinic, Yokohama, Japan. arai-cl@n04.itscom.net
authors.forename: Keiko
authors.initials: K
authors.lastname: Arai
authors.forename: Hajime
authors.initials: H
authors.lastname: Maeda
authors.forename: Sin-ichiro
authors.initials: S
authors.lastname: Sirabe
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Hirao
authors.forename: Setsuko
authors.initials: S
authors.lastname: Hirao
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007564:Japan / Q000453:epidemiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D014230:Triazoles; C517652:hemoglobin A1c protein, human; C057619:glimepiride