title: Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control via different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes.
abstract: This study aimed to explore the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin and the biguanide metformin on the secretion of insulin and glucagon, as well as incretin levels, in Japanese subjects with type 2 diabetes mellitus poorly controlled with insulin monotherapy. This was a single-center, randomized, open-label, parallel group study, enrolling 25 subjects. Eleven patients (hemoglobin A1c [HbA1c] 8.40 ± 0.96%) and 10 patients (8.10 ± 0.54%) on insulin monotherapy completed 12-week treatment with sitagliptin (50 mg) and metformin (750 mg), respectively. Before and after treatment, each subject underwent a meal tolerance test. The plasma glucose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), C-peptide, and glucagon responses to a meal challenge were measured. HbA1c reductions were similar in patients treated with sitagliptin (0.76 ± 0.18%) and metformin (0.77 ± 0.17%). In the sitagliptin group, glucose excursion during a meal tolerance test was reduced and accompanied by elevations in active GLP-1 and active GIP concentrations. C-peptide levels were unaltered despite reduced glucose responses, while glucagon responses were significantly suppressed (-7.93 ± 1.95% of baseline). In the metformin group, glucose excursion and incretin responses were unaltered. C-peptide levels were slightly increased but glucagon responses were unchanged. Our data indicate that sitagliptin and metformin exert different effects on islet hormone secretion in Japanese type 2 diabetic patients on insulin monotherapy. A glucagon suppressing effect of sitagliptin could be one of the factors improving blood glucose control in patients inadequately controlled with insulin therapy.
authors.affiliation: Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Asami
authors.initials: A
authors.lastname: Furukawa
authors.forename: Minami
authors.initials: M
authors.lastname: Kosuda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakazaki
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000819:agonists / Q000097:blood; D005934:Glucagon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000097:blood; D050416:Glucagon-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D019518:Postprandial Period; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human