Efficacy and safety profile of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease

Expert Opin Drug Saf. 2020 Mar;19(3):243-256. doi: 10.1080/14740338.2020.1733967. Epub 2020 Mar 2.

Abstract

Introduction: Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have a complex relationship with the kidney so that their use in patients with type 2 diabetes (T2DM) and diabetic kidney disease (DKD) has long been challenged.Areas covered: SGLT2is in patients with DKD are discussed: renal mechanisms of action, PK/PD characteristics, clinical use in patients with stage 3 DKD, effects on estimated glomerular filtration rate (eGFR) and albuminuria, cardiovascular, and renal outcomes according to renal function, overall and renal safety, SGLT2is new place in updated guidelines.Expert opinion: Whereas initial concerns (reduced glucose-lowering efficacy, early reduction in eGFR) led to restrictions in the use of SGLT2is in patients with DKD, recent positive observations have completely reversed the scene. Indeed, albuminuria is reduced and eGFR is preserved in the long term by SGLT2is. A significant reduction in cardiovascular events and hard renal outcomes was reported even in patients with eGFR 30-60 mL/min/1.73 m2. The overall safety profile of SGLT2is is not altered in patients with mild to moderate DKD, with a reduced (rather than increased) risk of acute renal injury. This positive benefit/risk balance led recent guidelines to recommend SGLT2is in patients with T2DM and mild to moderate DKD, especially if albuminuria.

Keywords: Cardiovascular disease; SGLT2 inhibitor; chronic kidney disease; gliflozin; guidelines; safety; type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / drug therapy*
  • Glomerular Filtration Rate / drug effects
  • Guidelines as Topic
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use
  • Kidney / drug effects
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacokinetics
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors