The Diabetes Unit, Hadassah University Hospital, Jerusalem, Israel; The Endocrine Service, Hadassah University Hospital, Jerusalem, Israel.
Diabetes Obes Metab. 2015 May;17(5):487-94. doi: 10.1111/dom.12445. Epub 2015 Feb 25.
To study the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on glycaemic stability and β-cell function in the SAVOR-TIMI 53 trial.
We randomized 16,492 patients with type 2 diabetes (T2D) to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of ≥ 0.5% post-randomization; (ii) the initiation of new antidiabetic medications for ≥ 3 months; or (iii) an increase in dose of oral antidiabetic medication or ≥ 25% increase in insulin dose for ≥ 3 months. β-cell function was assessed according to fasting homeostatic model 2 assessment of β-cell function (HOMA-2β) values at baseline and at year 2 in patients not treated with insulin.
Compared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68-0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of ≥ 0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA-2β values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001).
Saxagliptin improved glycaemia and prevented the reduction in HOMA-2β values. Saxagliptin may reduce the usual decline in β-cell function in T2D, thereby slowing diabetes progression.
研究二肽基肽酶-4 抑制剂沙格列汀对 SAVOR-TIMI 53 试验中血糖稳定性和β细胞功能的影响。
我们将 16492 例 2 型糖尿病（T2D）患者随机分为沙格列汀或安慰剂组，加用当前的降糖药物，并随访中位数 2.1 年。血糖不稳定定义为：（i）随机化后糖化血红蛋白（HbA1c）升高≥0.5%；（ii）≥3 个月开始使用新的降糖药物；或（iii）≥3 个月口服降糖药物剂量增加≥25%或胰岛素剂量增加≥25%。在未使用胰岛素治疗的患者中，根据基线和第 2 年的空腹稳态模型 2 评估β细胞功能（HOMA-2β）值评估β细胞功能。
与安慰剂相比，沙格列汀治疗组血糖不稳定的发展减少（风险比 0.71；95%置信区间 0.68-0.74；p<0.0001）。与安慰剂相比，沙格列汀治疗组 HbA1c 升高≥0.5%的发生率降低了 35.2%；胰岛素起始率降低了 31.7%，口服降糖药物或胰岛素剂量的增加分别降低了 19.5%和 23.5%（均 p<0.0001）。与安慰剂相比，第 2 年时，安慰剂组的 HOMA-2β 值下降了 4.9%，而沙格列汀组则增加了 1.1%（p<0.0001）。
沙格列汀改善了血糖，并防止了 HOMA-2β 值的降低。沙格列汀可能会降低 T2D 中β细胞功能的常见下降，从而减缓糖尿病的进展。
