Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control <i>via</i> different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes
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- Otsuka Yuichiro
- Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan
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- Yamaguchi Suguru
- Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan
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- Furukawa Asami
- Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan
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- Kosuda Minami
- Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan
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- Nakazaki Mitsuhiro
- Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan
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- Ishihara Hisamitsu
- Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo 173-8610, Japan
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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.
Journal
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- Endocrine Journal
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Endocrine Journal 62 (2), 133-143, 2015
The Japan Endocrine Society