RT Journal Article
SR Electronic
T1 Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α<sup>1-67</sup> in Patients With Type 2 Diabetes
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 1073
OP 1081
DO 10.2337/dc17-0061
VO 40
IS 8
A1 Lovshin, Julie A.
A1 Rajasekeran, Harindra
A1 Lytvyn, Yulyia
A1 Lovblom, Leif E.
A1 Khan, Shajiha
A1 Alemu, Robel
A1 Locke, Amy
A1 Lai, Vesta
A1 He, Huaibing
A1 Hittle, Lucinda
A1 Wang, Weixun
A1 Drucker, Daniel J.
A1 Cherney, David Z.I.
YR 2017
UL http://care.diabetesjournals.org/content/40/8/1073.abstract
AB 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)-1α 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-1α1-67 and decreased truncated plasma SDF-1α3-67. 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-1α1-67. 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.