Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes

Abstract

DPP-4 inhibition promotes a distal tubular natriuresis in conjunction with increased levels of intact SDF-1α. 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.

Response to Comment on Lovshin et al. Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes. Diabetes Care 2017;40:1073-1081

“…We thank van Baar et al (1) for their interest in our study (2). We agree that the chronic natriuretic effect(s) of the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin occurred in the early postprandial state (3 h after a standardized liquid meal during a euglycemic clamp).…”

The renoprotective effect and safety of a DPP-4 inhibitor, sitagliptin, at a small dose in type 2 diabetic patients with a renal dysfunction when changed from other DPP-4 inhibitors: REAL trial

“…Activation and prolongation of their physiological activities by DPP-4 inhibition can lead to actions such as natriuresis, improvement of inflammation, suppression of the sympathetic nervous activity, suppression of the renin-angiotensin system, vasodilatation, and cytoprotection [33,34]. Natriuresis has been reported to occur by DPP-4 inhibitor independent of GLP-1 receptor [24] because DPP-4 inhibitors have directly reduced the expression of sodium-proton exchanger 3 (NHE3) protein [35], and promoted a distal tubular natriuresis through SDF-1α [36]. Furthermore, DPP-4 inhibitors may enhance the secretion of BNP or ANP from the atrium, resulting in natriuresis [37].…”

Renal Hyperfiltration in Adolescents with Type 2 Diabetes: Physiology, Sex Differences, and Implications for Diabetic Kidney Disease

“…In addition, SGLT2 inhibition improves insulin sensitivity in adults (17). Amongst newer antihyperglycemic agents, attenuation of hyperfiltration and improvement in intrarenal hemodynamic function appears to be unique to SGLT2 inhibitors, and has not been observed with glucagon-like peptide (GLP)1 receptor agonists or dipeptidyl pepetidase-4 inhibitors in adults with T2D (18–20). A better understanding of the mechanisms contributing to hyperfiltration and its relationship with IR and progression of DKD in youth-onset T2D is critical to inform medical decision making and improve the renal health and mortality of children with T2D.…”