Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES I 6-19

• 40% reduction in overall decline in kidney function (eGFR, need for dialysis or renal death) • NNT: Was not reported The Diabetes Canada CPGs have determined the level of evidence for canagliflozin for CV protection to be weaker (in comparison to empagliflozin) due to the lack of benefit on all-cause or CV mortality and the increased risk of fractures and amputation (24). Of note: Although in CANVAS, canagliflozin was associated with a 1.97-fold increased risk of lower extremity amputation compared with placebo, in the more recent C anagliflozin and R enal E ndpoints in D iabetes with E stablished N ephropathy C linical E valuation (CREDENCE) trial, canagliflozin was not associated with an increased risk for amputations nor fractures. To address these findings in practice, for ALL people on SGLT2i therapy, good foot care is always recommended – particularly in those with high-risk feet (i.e. loss of protective sensation, previous foot ulcer or amputation). The C anagliflozin and R enal E ndpoints in D iabetes with E stablished N ephropathy C linical E valuation (CREDENCE) trial was the first trial to evaluate the effect of a SGLT2i on progression of kidney disease as a primary outcome in people with type 2 diabetes and established CKD with significant proteinuria. Eligibility criteria: • ≥30 y.o. with type 2 diabetes with eGFR 30 to 90 mL/min/1.73m 2 and albuminuria → This was the first trial to demonstrate the safety and benefit of the use of SGLT2i in baseline eGFR as low as 30mL/min/1.73m 2

Treatment with canagliflozin 100mg resulted in a: • 30% reduction in progression of CKD (statistical significance, primary outcome) • 20% reduction in MACE (statistical significance, secondary outcome)

The Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes Study ( DECLARE ) demonstrated noninferiority in CV events compared to placebo treatment (209). Treatment with dapagliflozin resulted in a: • No significant reduction in CV death, non-fatal MI or non-fatal stroke • 27% reduction in secondary outcome of reduction in HHF • 24% reduction in overall decline in kidney function (eGFR, new ESRD or renal death), secondary outcome • NNT: Was not reported