Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Department of Cardiovascular Medicine, NTT East Japan Sapporo Hospital, Sapporo, Japan.
Cardiovasc Diabetol. 2017 Oct 10;16(1):125. doi: 10.1186/s12933-017-0607-6.
Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin.
In this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500-750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed.
Ninety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (- 0.80 ± 0.38% vs. - 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (- 0.51 [- 1.08-0.06]% vs. - 0.58 [- 1.20-0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66-0.62; p < 0.01), the change did not differ significantly between the two groups (- 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01).
Regardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.
二肽基肽酶-4（DPP-4）抑制剂在 2 型糖尿病患者的动脉粥样硬化早期可能具有保护作用，尽管最近的随机安慰剂对照研究并未显示其在晚期动脉粥样硬化中有类似作用。因此，我们研究了与大剂量二甲双胍相比，DPP-4 抑制剂对内皮功能和血糖代谢的疗效。
本研究为多中心、开放标签、前瞻性、随机、平行组比较研究，纳入了正在接受低剂量二甲双胍（500-750mg/天）治疗的 2 型糖尿病患者，并随机分为维格列汀（一种 DPP-4 抑制剂）加量组（Vilda 组）或二甲双胍加倍组（高剂量组），治疗 12 周。治疗前后评估血流介导的舒张功能（FMD）和血清代谢标志物。此外，还评估了血糖控制和代谢参数。
共纳入 97 例患者（年龄 58.7±11.0 岁；体重指数 25.9±4.4kg/m2；糖化血红蛋白 7.3±0.5%；FMD 5.8±2.6%），8 例患者在研究结束时脱落。两组基线特征无显著差异。12 周后，Vilda 组的糖化血红蛋白水平较高剂量组显著改善（-0.80±0.38%比-0.40±0.47%；p<0.01）。然而，FMD 无显著差异（-0.51[-1.08-0.06]%比-0.58[-1.20-0.04]%）。尽管 Vilda 组载脂蛋白 B/载脂蛋白 A1 比值与基线相比显著降低（0.66-0.62；p<0.01），但两组间无显著差异（-0.04 比 0.00；p=0.27）。Vilda 组脂联素水平较高剂量组显著升高（0.75μg/ml 比 0.01μg/ml；p<0.01）。
无论血糖改善情况如何，维格列汀联合二甲双胍治疗并未影响内皮功能，但可能对 2 型糖尿病无晚期动脉粥样硬化患者的脂联素水平和血脂谱产生有利影响。
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