What is the role of SGLT2 inhibitors in the treatment of diabetic nephropathy?

Updated: Oct 09, 2019
  • Author: Vecihi Batuman, MD, FASN; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

There are several SGLT2 inhibitors under development or consideration by the US Food and Drug Administration (FDA), and canagliflozin (Invokana) is the first SGLT2 inhibitor approved for use in the United States. Canagliflozin inhibits renal glucose absorption in the proximal tubule, the site in the kidney where approximately 90% of glucose reabsorption occurs. This leads to increased excretion of glucose in the urine, which may help subjects lose up to 5 kg of weight over a year. The decreased glucose reabsorption is also accompanied by increased urinary excretion of sodium, which, in turn, may help with further blood pressure lowering, which could be an advantage in patients with diabetic kidney disease and hypertension.

At this time, the maximum dose in patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 is 100 mg once daily and it is not recommended in patients with an eGFR of less than 45 mL/min/1.73 m2. Increased glucosuria is believed to increase the risk of urinary tract infections, especially candidal infections, and more frequently in women. [31]

In April 2019, it was reported that the CREDENCE trial, a multicenter, randomized, double-blind, placebo-controlled study of 4401 patients, had shown that canagliflozin leads to a 30% reduction in the likelihood that patients with type 2 diabetes and chronic kidney disease will progress to end-stage kidney disease, and also significantly decreases the chances for major cardiovascular events. [32]


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