title: Low-dose glimepiride with sitagliptin improves glycemic control without dose-dependency in patients with type 2 diabetes inadequately controlled on high-dose glimepiride.
abstract: This randomized, prospective study was conducted in 76 subjects to assess whether low-dose (0.5-2 mg/day) glimepiride, in combination therapy with sitagliptin, improves glycemic control in a dose-dependent manner in Japanese patients with type 2 diabetes. Eligible subjects had been treated with glimepiride at doses of 3-6 mg/day for at least 3 months and had a HbA1c level of ≥6.9%. Subjects were randomly assigned to three treatment groups of reduced doses of glimepiride (0.5 mg/day, 1 mg/day, or 2 mg/day) in addition to sitagliptin for 24 weeks. The primary efficacy analysis evaluated the change in HbA1c from baseline to week 24. Secondary efficacy endpoints included the changes in fasting plasma glucose, insulin secretion capacity, and β-cell function. Safety endpoints included hypoglycemia and any adverse event. Despite dose reduction of glimepiride, combination therapy with sitagliptin induced significant improvements in HbA1c levels (-0.8%, p < 0.001). Insulin secretion parameters (CPI, SUIT) also increased significantly. There were no significant differences between groups in changes from baseline HbA1c, insulin secretion capacity, and β-cell function (proinsulin/insulin) at 24 weeks of combination therapy. Multivariate analysis showed that baseline HbA1c was the only predictor for efficacy of combination therapy with sitagliptin and low-dose glimeripide. No changes in body weight were noted and no symptomatic hypoglycemia was documented. These findings indicate that combination therapy with sitagliptin and low-dose glimepiride (0.5 mg/day) is both effective for glycemic control and safe in Japanese patients with type 2 diabetes inadequately controlled with high-dose glimepiride.
authors.affiliation: Center for Diabetes, Endocrinology and Metabolism, Shizuoka General Hospital, Shizuoka 420-8527, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Umayahara
authors.forename: Takako
authors.initials: T
authors.lastname: Yonemoto
authors.forename: Chika
authors.initials: C
authors.lastname: Kyou
authors.forename: Kae
authors.initials: K
authors.lastname: Morishita
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Tatsuhide
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D003928:Diabetic Nephropathies / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D054795:Incretins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007564:Japan; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D054795:Incretins; D007328:Insulin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D014230:Triazoles; C517652:hemoglobin A1c protein, human; C057619:glimepiride