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
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
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DOI：
10.1507/endocrj.ej14-0148
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发表时间：
2015-02-20
影响因子：
2
通讯作者：
Ishihara, Hisamitsu
中科院分区：
文献类型：
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作者：
Otsuka, Yuichiro;Yamaguchi, Suguru;Ishihara, Hisamitsu
本研究旨在探讨二肽基肽酶-4抑制剂西格列汀和双胍类二甲双胍对日本2型糖尿病患者胰岛素、胰高血糖素分泌及肠促胰岛素水平的影响。这是一项单中心、随机、开放标签、平行组研究，纳入25名受试者。胰岛素单药治疗组11例患者（血红蛋白A1c [HbA1c] 8.40 +/- 0.96%）和10例患者（8.10 +/- 0.54%）分别完成西格列汀（50 mg）和二甲双胍（750 mg） 12周的治疗。在治疗前后，每个受试者都进行了饮食耐受试验。测定血浆葡萄糖、胰高血糖素样肽-1 （GLP-1）、葡萄糖依赖性胰岛素性多肽（GIP）、c肽和胰高血糖素对食物刺激的反应。西格列汀（0.76 +/- 0.18%）和二甲双胍（0.77 +/- 0.17%）治疗的患者HbA1c降低相似。在西格列汀组，在餐耐量试验期间葡萄糖漂移减少，并伴有活性GLP-1和活性GIP浓度升高。尽管葡萄糖反应降低，但c肽水平没有改变，而胰高血糖素反应明显受到抑制（-7.93 +/- 1.95%的基线）。在二甲双胍组，葡萄糖漂移和肠促胰岛素反应没有改变。c肽水平略有升高，但胰高血糖素反应不变。我们的数据表明西格列汀和二甲双胍对胰岛素单药治疗的日本2型糖尿病患者胰岛激素分泌有不同的影响。西格列汀抑制胰高血糖素的作用可能是改善胰岛素治疗控制不充分的患者血糖控制的因素之一。
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.