Diabetes Centre, Department of Internal Medicine, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands.
Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, The Netherlands.
Diabetes Obes Metab. 2021 Aug;23(8):1851-1858. doi: 10.1111/dom.14410. Epub 2021 May 14.
To evaluate the effects of separate and combined use of the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin and the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on measures of kidney function.
In this prespecified secondary analysis of the DECREASE trial, we enrolled 66 obese patients with type 2 diabetes in a 16-week randomized double-blind placebo-controlled clinical trial to investigate the effects of dapagliflozin and exenatide twice daily, alone or in combination, versus placebo on 24-hour urinary albumin:creatinine ratio (UACR), creatinine and cystatin C-estimated glomerular filtration rate (GFR) and kidney injury molecule-1:creatinine ratio (KIM-1:Cr).
At week 16, the mean UACR change from baseline was -39.6% (95% confidence interval [CI] -58.6, -11.9; P = 0.001) in the combined exenatide-dapagliflozin group, -18.1% (95% CI -43.1, 18.0; P = 0.278) in the dapagliflozin group, -15.6% (95% CI -41.4, 21.6; P = 0.357) in the exenatide group and - 11.0% (95% CI -39.8, 31.5; P = 0.552) in the placebo group. Compared to placebo, UACR difference at week 16 in the exenatide-dapagliflozin group was -32.2% (95% CI -60.7, 16.9; P = 0.159). Effects were similar in 37 participants who were using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at baseline. Compared to placebo, in the exenatide-dapagliflozin group, an acute dip in estimated GFR was observed with creatinine-estimated GFR (-4.0 mL/min/1.73 m [95% CI -9.3, 1.2]; P = 0.129) and cystatin C-estimated GFR (-10.4 mL/min/1.73 m [95% CI -14.9, -5.8]; P < 0.001). The mean KIM-1:Cr difference in the combined treatment arm versus placebo was -43.8% (95% CI -73.5, 18.9; P = 0.129).
This prespecified secondary analysis suggests that combined therapy with exenatide and dapagliflozin may have synergistic effects on markers of kidney function compared to either therapy alone or placebo in obese patients with type 2 diabetes.
评估钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂达格列净和胰高血糖素样肽-1 受体激动剂（GLP-1RA）艾塞那肽单独和联合使用对肾功能指标的影响。
在 DECREASE 试验的这项预设二次分析中，我们招募了 66 名肥胖的 2 型糖尿病患者，进行了为期 16 周的随机双盲安慰剂对照临床试验，以研究达格列净和艾塞那肽每日两次、单独或联合使用与安慰剂相比对 24 小时尿白蛋白与肌酐比值（UACR）、肌酐和胱抑素 C 估计肾小球滤过率（eGFR）以及肾损伤分子-1 与肌酐比值（KIM-1:Cr）的影响。
在第 16 周时，与基线相比，联合使用艾塞那肽和达格列净组的 UACR 平均变化为 -39.6%（95%置信区间 [CI] -58.6，-11.9；P=0.001），达格列净组为 -18.1%（95% CI -43.1，18.0；P=0.278），艾塞那肽组为 -15.6%（95% CI -41.4，21.6；P=0.357），安慰剂组为 -11.0%（95% CI -39.8，31.5；P=0.552）。与安慰剂相比，在联合使用艾塞那肽和达格列净组，第 16 周时 UACR 的差异为 -32.2%（95% CI -60.7，16.9；P=0.159）。在基线时使用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂的 37 名参与者中，观察到的效果相似。与安慰剂相比，在联合使用艾塞那肽和达格列净组，使用肌酐估计肾小球滤过率（-4.0 mL/min/1.73 m [95% CI -9.3，1.2]；P=0.129）和胱抑素 C 估计肾小球滤过率（-10.4 mL/min/1.73 m [95% CI -14.9，-5.8]；P<0.001）时，估计肾小球滤过率会出现急性下降。与安慰剂相比，联合治疗组的平均 KIM-1:Cr 差异为 -43.8%（95% CI -73.5，18.9；P=0.129）。
这项预设的二次分析表明，与单独使用任何一种药物或安慰剂相比，肥胖的 2 型糖尿病患者联合使用艾塞那肽和达格列净可能对肾功能标志物具有协同作用。
