The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors

ABSTRACT

Understanding the role of the kidneys in type 2 diabetes mellitus (T2DM) has taken on an increased importance in recent years with the arrival of sodium–glucose co-transporter 2 (SGLT2) inhibitors — antihyperglycemic agents (AHAs) that specifically target the kidneys. This review includes an update on the physiology of the kidneys, their role in the pathophysiology of T2DM, and the mechanisms implicated in the development and progression of diabetic kidney disease, such as glomerular hyperfiltration and inflammation. It also discusses renal issues that could influence the choice of AHA for patients with T2DM, including special populations such as patients with concomitant chronic kidney disease. The most recent data published on the clinical efficacy and safety of the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and their effects on renal function are presented, showing how the renally mediated mechanisms of action of these agents translate into clinical benefits, including the potential for renoprotection. The observed positive effects of these agents on measures such as glucose control, estimated glomerular filtration rate, albumin-to-creatinine ratio, blood pressure, and body weight in patients both with and without impaired renal function suggest that SGLT2 inhibitors represent an important extension to the diabetes treatment armamentarium.

KEYWORDS:

• Kidney
• Pathophysiology
• Type 2 diabetes mellitus
• T2DM
• Sodium–glucose co-transporter 2
• SGLT2
• Nephropathy

Financial and competing interests disclosure

Medical writing and editorial support was provided by Sandrine Buisson, PhD, and Adriana Stan, PhD, of Excerpta Medica, and was funded by Janssen Scientific Affairs, LLC. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation. This review was sponsored by Janssen Scientific Affairs, LLC. The author received no direct compensation related to the development of the manuscript. Janssen Scientific Affairs, LLC was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. M Weir reports receiving fees for serving on steering committees from Amgen and Sandoz and consulting fees from AbbVie, Akebia Therapeutics, Amgen, AstraZeneca, Boston Scientific, Janssen, and Merck Sharp and Dohme. The author has 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.