Impact of SGLT2 inhibitors on the kidney in people with type 2 diabetes and severely increased albuminuria

ABSTRACT

Introduction

Diabetes is the most common cause of end-stage kidney disease. Therapies such as sodium-glucose co-transporter-2 inhibitors have been identified over the last decade as effective oral hypoglycemic agents that also confer additional cardio and kidney protection. Knowledge of their mechanism of action and impact on patients with diabetes and albuminuria is vital in galvanizing prescriber confidence and increasing clinical uptake.

Areas covered

This manuscript discusses the pathophysiology of diabetic kidney disease, patho-physiological mechanisms for sodium-glucose co-transporter-2 inhibitors, and their impact on patients with type 2 diabetes mellitus and albuminuric kidney disease.

Expert opinion

Sodium-glucose co-transporter-2 inhibitors reduce albuminuria with consequent benefits on cardiovascular and kidney outcomes in patients with diabetes and severe albuminuria. While they have been incorporated into guidelines, the uptake of these agents into clinical practice has been slow. Increasing the uptake of these agents into clinical practice is necessary to improve outcomes for the large number of patients with diabetic kidney disease globally.

P LAIN LANGUAGE SUMMARY

People with type 2 diabetes and severe urinary protein loss are at high risk of progression to kidney failure requiring dialysis or transplantation. Preventing or slowing down loss of kidney function is crucial to preventing kidney failure. This review will discuss how diabetic kidney disease occurs, how a new family of glucose-lowering agents, the sodium-glucose co-transporter-2 inhibitors, work and how they affect people with type 2 diabetes mellitus who also have protein leaking from their kidneys. It will also detail the current data that underpins the guideline recommendations for use of these agents in the management of patients with and without diabetes.

KEYWORDS:

• Diabetes
• kidney disease
• albuminuria sodium-glucose co-transporter-2 inhibitors
• hypoglycemic agents

Article highlights

• Interventions that reduce albuminuria have a significant impact on reducing the progression of renal disease in patients with diabetic kidney disease.

• Multiple large randomized clinical trials have provided conclusive evidence that SGLT2-inhibitors reduce albuminuria and have notable cardiovascular and kidney protective effects.

• The evidence suggests that the kidney protection benefits extend beyond those purely from albuminuria regression.

• Despite the inclusion of SGLT-2 inhibitors in guideline recommendations, uptake in clinical practice has been limited.

• Improved access, better uptake, along with a more detailed understanding of their mechanism of action will be critical in realizing their true potential to curb the worsening global burden of chronic kidney disease.

Declaration of interest

V Perkovic has led or served on the Steering Committees of trials funded by the National Health and Medical Research Council of Australia, Janssen, AbbVie, Bayer, GSK, Boehringer Ingelheim, Eli Lilly, Gilead, Novartis, Novo Nordisk, Retrophin/Travere, Tricida and Pfizer; has received honoraria for scientific presentations and/or advisory board attendance from AbbVie, Amgen, AstraZeneca, Bayer, Baxter, Boehringer Ingelheim, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pharmalink, Pfizer, Reata, Relypsa, Roche, Sanofi and Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.