Sato Ai, Takei Masahiro, Hiramatsu Kunihide, Takeda Teiji, Miyamoto Takahide, Yamazaki Masanori, Sato Yoshihiko, Komatsu Mitsuhisa
Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
AS and MT equally contributed to this study.
J Clin Med Res. 2019 Jan;11(1):15-20. doi: 10.14740/jocmr3632. Epub 2018 Dec 3.
This prospective randomized, multicenter, open-label, comparative study was performed to analyze the effects of sitagliptin on glycemic control and maintenance of beta-cell function in patients with poorly controlled type 2 diabetes treated with low-dose glimepiride.
Forty-one patients with type 2 diabetes mellitus treated with low-dose glimepiride (≤ 2 mg/day) were prospectively enrolled in this study (age: 20 - 75 years; hemoglobin A1c (HbA1c): 7.4- 9.4%). The patients were randomized into two groups: the glimepiride (G) group, in which glimepiride dose was increased gradually to 6 mg/day, and the sitagliptin (S) group, in which sitagliptin was added at a dose of 50 mg/day.
HbA1c level was significantly decreased after 24 weeks, but not 12 weeks, in the G group, while a significant decrease was seen after 12 weeks in the S group. Although there were no significant differences in HbA1c level at 24 weeks between the two groups (P = 0.057). The overall trend of changes in HbA1c level suggested that the glucose-lowering effects were superior in the S group. Furthermore, a significant change in fasting glucose was seen in the S group, but not in the G group. Glycemic control target was achieved in 36.7% and 16.7% patients in the S group and the G group, respectively. The proinsulin/insulin (P/I) ratio was significantly increased in the G group, whereas it tended to decrease in the S group. After 24 weeks of treatment, no significant difference was observed in the P/I ratio between the two groups, whereas a significant difference was noted in the ΔP/I (amount of change). Albuminuria tended to increase in the G group compared with the S group.
The results of the present study suggested that sitagliptin effectively lowered hyperglycemia and that it may have a protective effect on pancreatic beta-cells when combined with a low dose of glimepiride. Therefore, sitagliptin may represent a useful combination therapy with low-dose sulfonylurea, not only for achieving glycemic control but also for protection of pancreatic beta-cells.
本前瞻性随机、多中心、开放标签的对照研究旨在分析西他列汀对接受低剂量格列美脲治疗的2型糖尿病控制不佳患者血糖控制及β细胞功能维持的影响。
41例接受低剂量格列美脲（≤2mg/天）治疗的2型糖尿病患者前瞻性纳入本研究（年龄：20 - 75岁；糖化血红蛋白（HbA1c）：7.4 - 9.4%）。患者被随机分为两组：格列美脲（G）组，格列美脲剂量逐渐增加至6mg/天；西他列汀（S）组，加用50mg/天的西他列汀。
G组在24周后HbA1c水平显著降低，但12周时未降低，而S组在12周后即出现显著降低。尽管两组在24周时HbA1c水平无显著差异（P = 0.057）。HbA1c水平变化的总体趋势表明S组的降糖效果更佳。此外，S组空腹血糖有显著变化，而G组无。S组和G组分别有36.7%和16.7%的患者达到血糖控制目标。G组胰岛素原/胰岛素（P/I）比值显著升高，而S组则呈下降趋势。治疗24周后，两组间P/I比值无显著差异，但在ΔP/I（变化量）方面存在显著差异。与S组相比，G组蛋白尿有增加趋势。
本研究结果表明，西他列汀可有效降低高血糖，与低剂量格列美脲联合使用时可能对胰腺β细胞有保护作用。因此，西他列汀可能是一种有用的与低剂量磺脲类药物的联合治疗方法，不仅可实现血糖控制，还可保护胰腺β细胞。
