期刊
DIABETES CARE
卷 40, 期 8, 页码 1073-1081出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc17-0061
关键词
-
资金
- Merck Sharp Dohme
- Diabetes Action Canada
- Strategic Patient-Oriented Research initiative by Canadian Institutes of Health Research
OBJECTIVE Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium-glucose cotransporter 2 (SGLT2) inhibitors, we examined whether and how sitagliptin modulates fractional sodium excretion and renal and systemic hemodynamic function. RESEARCH DESIGN AND METHODS We studied 32 patients with type 2 diabetes in a prospective, double-blind, randomized, placebo-controlled trial. Measurements of renal tubular function and renal and systemic hemodynamics were obtained at baseline, then hourly after one dose of sitagliptin or placebo, and repeated at 1 month. Fractional excretion of sodium and lithium and renal hemodynamic function were measured during clamped euglycemia. Systemic hemodynamics were measured using noninvasive cardiac output monitoring, and plasma levels of intact versus cleaved stromal cell-derived factor (SDF)-1 alpha were quantified using immunoaffinity and tandem mass spectrometry. RESULTS Sitagliptin did not change fractional lithium excretion but significantly increased total fractional sodium excretion (1.32 +/- 0.5 to 1.80 +/- 0.01% vs. 2.15 +/- 0.6 vs. 2.02 +/- 1.0%, P = 0.012) compared with placebo after 1 month of treatment. Moreover, sitagliptin robustly increased intact plasma SDF-1 alpha 1-67 and decreased truncated plasma SDF-1 alpha 3-67. Renal hemodynamic function, systemic blood pressure, cardiac output, stroke volume, and total peripheral resistance were not adversely affected by sitagliptin. CONCLUSIONS DPP-4 inhibition promotes a distal tubular natriuresis in conjunction with increased levels of intact SDF-1 alpha 1-67. Because of the distal location of the natriuretic effect, DPP-4 inhibition does not affect tubuloglomerular feedback or impair renal hemodynamic function, findings relevant to using DPP-4 inhibitors for treating type 2 diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据