title: Efficacy and safety of repaglinide added to sitagliptin in Japanese patients with type 2 diabetes: A randomized 24-week open-label clinical trial.
abstract: Although sitagliptin and repaglinide monotherapies improve postprandial hyperglycemia, the long-term effects and safety of their combination has not been examined. In this randomized 24-week trial of Japanese patients with poor control (HbA1c 7.0-8.5%) by sitagliptin, we divided 40 patients randomly into two equal groups of the repaglinide add-on to sitagliptin (ADD-ON, n=20), or sitagliptin switched to repaglinide (SWITCH, n=20). The meal tolerance test was carried out at weeks 0 and 24. The primary outcomes were changes in HbA1c and area under the curves (AUC) of glucose from the baseline to week 24. The mean change in HbA1c from baseline to week 24 was larger in the ADD-ON (-0.87±0.63%, mean±SD), compared with the SWITCH (0.03±0.65%, p=0.000). Significant improvements were noted in the mean changes in fasting glucose and AUCs of glucose in the ADD-ON vs. SWITCH (p=0.007 and p=0.000). Insulin secretion relative to glucose elevation (ISG; defined as AUC insulin/AUC glucose) increased significantly in the ADD-ON, although the mean change in fasting insulin level was significantly decreased in the ADD-ON (p=0.015 and p=0.026). The AUC of glucagon was significantly lower at 24-week relative to baseline in the ADD-ON, but was not significant in the two groups (p=0.047 and p=0.056, respectively). The combination therapy produced significant reductions in HbA1c, AUC of glucose and fasting glucose compared with switching to repaglinide without weight gain or severe hypoglycemia. The improved glycemic control with this combination therapy may be at least in part due to augmentation of repaglinide-induced insulin secretion by sitagliptin.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishimura
authors.forename: Shuki
authors.initials: S
authors.lastname: Usui
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumashiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchino
authors.forename: Azusa
authors.initials: A
authors.lastname: Yamato
authors.forename: Daijiro
authors.initials: D
authors.lastname: Yasuda
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Mori
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D019518:Postprandial Period; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human; C072379:repaglinide