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SGLT2 Inhibitors for Kidney Disease

Sep 1, 2020

Author: Tracie Comer, PharmD Candidate 2020  | Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP 

 A 56-year old male with type 2 diabetes and stage 3 chronic kidney disease contacted us recently regarding his new prescription for the SGLT2 inhibitor canagliflozin (Invokana). While his diabetes was reasonably well controlled, with an A1C of 7.2%, his provider felt he may benefit from the kidney protective effects of canagliflozin (his most recent eGFR was 47 mL/min/1.73 m2, which has been stable over the last year). When the new prescription for canagliflozin was written, his medication regimen was as follows: 

  • Metformin ER 500 mg twice daily 
  • Insulin glargine 14 units mg once daily in the morning 
  • Lisinopril 20 mg once daily             
  • Atorvastatin 20 mg once daily      
  • Melatonin 1 mg once daily as needed 
  • Multivitamin (Centrum Silver) 1 tablet once daily 

After reading over the medication leaflet, the patient became concerned as he read canagliflozin has been associated with “reports of sudden worsening of kidney function” in people with type 2 diabetes.1 


To address his concerns, we educated him about recent evidence showing that canagliflozin can slow the progression of kidney disease in people with type 2 diabetes.2 While there is a theoretical risk of volume depletion and acute kidney injury (AKI) with SGLT2 inhibitors, evidence from kidney outcome trials suggests that the risk of AKI is actually reduced with SGLT2 inhibitor use.3 It is prudent, however, to exercise caution in patients at high risk for AKI, such as those on diuretics who may be prone to dehydration. We discussed the importance of adequate hydration and encouraged him to contact his prescriber and/or pharmacist with any other concerns. We also counseled him to check his blood glucose more frequently after starting canagliflozin and to be aware of signs and symptoms of hypoglycemia. While SGLT2 inhibitors lower blood glucose less in those with reduced kidney function, it is still important to be cautious about potential hypoglycemia when adding an SGLT2 inhibitor to background insulin or sulfonylurea therapy. 

Lessons learned: 

  • Agents from the SGLT2 inhibitor class of medications have shown benefit in slowing progression of diabetic kidney disease, with a reduced risk of AKI noted in kidney outcome trials. 
  • People with kidney disease started on an SGLT2 inhibitor to slow kidney disease progression should be counseled about why the medication is being used and strategies for risk mitigation, such as avoidance of dehydration and hypoglycemia. 



  1. Invokana (canagliflozin) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, INC; Revised January 2020 
  2. Perkovic V, Jardine M, Neal B et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019;380(24):2295-2306. doi:10.1056/nejmoa1811744 
  3. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Enocrinol2019;7:845-854 


Tracie Comer, PharmD Candidate 2020 

Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP 


See more about SGLT2 inhibitors in our therapy center.