SGLT2 inhibitors, sodium and off-target effects: an overview
- PDF / 1,563,951 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 7 Downloads / 217 Views
REVIEW
SGLT2 inhibitors, sodium and off‑target effects: an overview Antonio De Pascalis1 · Giuseppe Cianciolo2 · Irene Capelli2 · Giuliano Brunori3 · Gaetano La Manna2 Received: 17 May 2020 / Accepted: 14 August 2020 © Italian Society of Nephrology 2020
Abstract Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs that in addition to emerging as an effective antihyperglycemic treatment have been shown to improve, in several trials, both renal and cardiovascular outcomes. In consideration of the renal site of action and the associated osmotic diuresis, a negative sodium balance has been postulated during SGLT2i administration. Actually, sodium and water depletion may contribute to some positive actions of SGLT2i but evidence is far from being conclusive and the real physiologic effects of SGLT2i on sodium remain largely unknown. Indeed, no study has yet investigated how SGLT2i change sodium balance in the long term and especially the pathways through which the natriuretic effect is expressed. Furthermore, several experimental studies have recently identified different pathways, not directly linked to tubular sodium handling, which could contribute to the renal and cardiovascular benefits associated with SGLT2i. This paper will review the evidence of SGLT2i action on sodium transporters, their offtarget effects and their potential role on kidney protection. Keywords Diabetic nephropathy · Sodium · Sodium-glucose cotransporter 2 inhibitors
Introduction Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs that in addition to emerging as an effective antihyperglycemic treatment have been shown to improve, in several trials, both renal and cardiovascular outcomes. Until recently, diabetologists have not routinely prescribed SGLT2i , which were thought of solely as glucose-lowering drugs. However, the totality of the data would suggest that SGLT2i are agents that reduce cardiorenal risk and lower glucose as a side effect. Actually, none of the initially published trials had planned kidney events as a primary endpoint nor had they been designed to provide definitive information on the potential renal protection
* Antonio De Pascalis [email protected] 1
Nephrology, Dialysis and Renal Transplantation Unit, Vito Fazzi Hospital, Lecce, Italy
2
Nephrology, Dialysis and Renal Transplant Unit, Department of Experimental Diagnostic and Specialty Medicine (DIMES), S. Orsola‑Malpighi Hospital, University of Bologna, Bologna, Italy
3
Nephrology and Dialysis Unit, Hospital of Trento, Trento, Italy
associated with SGLT2 inhibition [1–6]. Before these agents could be routinely employed as first-line therapy in patients with diabetic kidney disease (DKD), further results from clinical trials designed ad hoc were necessary. The CREDENCE study expanded our understanding by showing a significant reduction (30%) in the risk of the composite endpoint of end-stage kidney disease (dialysis, transplantation, or a sustained es
Data Loading...
