Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES | 6-

with an eGFR > 30mL/min/1.73m 2 at baseline. At an equal grading of level of evidence: • canagliflozin 100mg/300mg (CANVAS) • dapagliflozin 10mg (DECLARE TIMI 58)

CV outcomes in persons with Heart Failure (HF) : SGLT2i evidence :

Studies investigating the use of SGLT2i agents in people with a history of HF with an eGFR > 30mL/min/1.73m 2 at baseline can be summarized from strongest evidence to least strong evidence as: • dapagliflozin 10mg (DAPA-HF → in persons with reduced ejection fraction, HFrEF) o first CVOT to test SGLT2i in a majority population without type 2 diabetes (42% had T2DM at baseline) o association with lower risk of worsening HF and all-cause mortality • canagliflozin 100mg/300mg (CANVAS) • empagliflozin 10mg/25mg (EMPA REG OUTCOME) Of note, the results of EMPEROR-REDUCED and EMPEROR-PRESERVED were not available at the time of the Diabetes Canada Pharmacologic Glycemic Management of Type 2 Diabetes in Adults: 2020 update and are therefore not discussed.

Cardiorenal outcomes in persons with CKD : GLP-1 RA evidence : Two GLP-1 RA have demonstrated reduced MACE outcomes: • Liraglutide 1.8mg (LEADER) • Semaglutide 0.5mg or 1mg (SUSTAIN-6)

SGLT2i evidence : Studies investigating the use of SGLT2i agents in people with CKD and an eGFR > 30mL/min/1.73m 2 at baseline can be summarized from strongest evidence to least strong evidence to reduce the risk of progression of nephropathy as: • Canagliflozin 100mg (CREDENCE) o first trial to evaluate SGLT2i on progression of kidney disease as a primary outcome in people with T2DM and established CKD with significant proteinuria o demonstrated → reduction in progression of primary outcome of CKD → lower risk of the secondary outcome of MACE • dapagliflozin 10mg (DECLARE TIMI 58) • empagliflozin 10mg (EMPA REG OUTCOME)

Zelniker et. al’s metanalysis ranked the following SGLT2i equally strong, Grade A, Level 1, as having evidence to show that SGLT2i can reduce the risk of HHF among adults with type 2 diabetes with CKD with an eGFR > 30mL/min/1.73m 2 at baseline

• Canagliflozin 100mg • dapagliflozin 10mg • empagliflozin 10mg