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  ACUTE AND CHRONIC KIDNEY DISEASE: SGLT2 inhibitors & risk of diabetic ketoacidosis (Sep. 2020)   A cohort study from Canad...


ACUTE AND CHRONIC KIDNEY DISEASE: SGLT2 inhibitors & risk of diabetic ketoacidosis (Sep. 2020)


A cohort study from Canada & UK that conducting almost 350,000 ptns in addition to 500 diabetic ketoacidosis (DKA) events, SGLT2 inhibitors (dapagliflozin (Forxiga), canagliflozin, empagliflozin), in comparison with dipeptidyl peptidase 4 (DPP-4) inhibitors, were currently complicated by a higher risk of DKA (a reported incidence 2.03 vs 0.75 /1000 person-ys). SGLT2 inhibitors should NOT be used with type 1 DM or with type 2 DM that was accompanied with factors that enhance the DKA development (e.g., pancreatic malfunction, drug addiction or alcohol abuse).  


Dose of Dapagliflozin (Forxiga) in adults with Renal dysfunction:

I. eGFR > 45 mL/minute/1.73 m2: No dosage adjustment necessary.    😚


II. eGFR 30 - <45 mL/minute/1.73 m2:

DM type II:

Ø  Hyperglycemia: The US manufacturer does NOT recommend use; use in other countries is variable   (ADA 2020).

Ø  Ptns with heart failure and/or atherosclerotic CVS: No dosage adjustment necessary for ptns with HF. The manufacturer in US states there is insufficient data supporting a dose recommendation in ptns without HF.

Ø  Diabetic kidney disease (off-label use): Some experts use dapagliflozin off label at a dose of 5 mg once/day in ptns with heavy albuminuria (e.g., urinary albumin >300 mg/d). (Perkovic 2020; Neuen 2019; Wiviott 2019).

Ø  Heart failure with EF decline: No dose adjustment is required.


III. eGFR <30 mL/minute/1.73 m2:

DM, type II: for hyperglycemia control: contraindicated.   

Use in ptns with HF and/or ptns with or at risk for atherosclerotic CVS disease: The US manufacturer states there is insufficient data to support a dose recommendation.                                                                                                                              Use in ptn with diabetic kidney disease (off-label use): Dapagliflozin should NOT be started; in ptns previously established on dapagliflozin, some experts continue use off-label with dose of 5 mg once daily (Perkovic 2020).                                                     

 HF with low EF:  no sufficient data to support dose recommendation.                                                         

ESRD, HDX: contraindicated.  

Douros A, Lix LM, Fralick M, et al. Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis: A Multicenter Cohort Study. Ann Intern Med 2020; 173:417.