Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES | 6- Graded at an equal level of evidence, the following has demonstrated a reduction in the risk of HHF among persons with type 2 diabetes with pre-existing CVD with an eGFR > 30mL/min/1.73m 2 at baseline and is further supported by the meta-analysis by Zelniker et. al., • Canagliflozin 100mg/300mg (CANVAS program, including CANVAS and CANVAS-R) • Dapagliflozin 10mg (DECLARE TIMI 58) • Empagliflozin 10mg/25mg (EMPA-REG OUTCOME) Graded at an equal level of evidence, the following has been shown to reduce progression of nephropathy as a secondary outcome in people with CVD with an eGFR > 30mL/min/1.73m 2 at baseline and is further supported by the meta-analysis by Zelniker et. al., • Canagliflozin 100mg/300mg (CANVAS program, including CANVAS and CANVAS-R) • Dapagliflozin 10mg (DECLARE TIMI 58) • Empagliflozin 10mg/25mg (EMPA-REG OUTCOME)

Primary CV prevent ion in persons with ASCVD : GLP-1 RA evidence :

Studies investigating the cardiorenal benefits of antihyperglycemic agents have included individuals who do not have established ASCVD, CKD, nor heart failure with, in order of strongest to less strong evidence for:

• Dulaglutide 1.5mg (REWIND) → 68.5% did not have CVD at baseline • Liraglutide 1.8mg (LEADER) → 18% did not have CVD at baseline

• Semaglutide 0.5mg or 1mg (SUSTAIN-6) → 41% did not have CVD at baseline, but lower grading of evidence than LEADER as the hypothesis for CV benefit superiority was not prespecified in SUSTAIN-6 SGLT2i evidence : All EMPA-REG and the majority of CANVAS participants had ASCVD — and of the one-third of participants in CANVAS who did not have CVD, a significant decrease in the primary endpoint was only found in those with CVD. However, DECLARE TIMI 58 was the first SGLT2i CVOT to include a majority of participants with CV risk factors (59%) . While DECLARE TIMI 58 did not find statistical significance for reduction of MACE, the results allowed for evidence to support: • Dapagliflozin 10mg (DECLARE TIMI 58) o no statistical significance for reduction of MACE o association with reduction of HHF and progression of kidney disease in people without existing CVD (statistical significance, but not a primary outcome of the trial) Evidence to support a reduction in the risk of HHF among persons with type 2 diabetes without pre-existing CVD with an eGFR > 30mL/min/1.73m 2 at baseline is provided by the meta-analysis by Zelniker et. al. At an equal grading of level of evidence:

• dapagliflozin 10mg (DECLARE TIMI 58) • canagliflozin 100mg/300mg (CANVAS)

Zelniker et. al’s metanalysis also provided evidence to show that SGLT2i can reduce progression of nephropathy as a secondary outcome in people with multiple CV risk factors