Table 7.4. Recommendations for use of SGLT2 inhibitors in preventing hospitalizations for HF in type 2 diabetes patients.

Recommendations	Class	LE	Comments	Table 2018	Ref.
SGLT2 inhibitors (canagliflozin, dapagliflozin or empagliflozin) to prevent hospitalization for HF in patients with type 2 diabetes and cardiovascular risk factors for atherosclerosis or established atherosclerotic cardiovascular disease.	I	A	NEW: SGLT2i are useful to reduce hospitalization for heart failure in patients with DM2.	Item 5.2 (page 451)	99–101
SGLT2 inhibitors (dapagliflozin or empagliflozin) as initial antidiabetic medication associated or not with metformin in HFrEF patients.	I	A	NEW: SGLT2i are useful for diabetes treatment and reduction of cardiovascular and renal events.	New	102
The benefits of SGLT2i in type 2 diabetes (DM2) patients were first described in the EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, published in 2015, which assessed empagliflozin use in patients with DM2, established cardiovascular disease, and receiving standard treatment.99 Among those who received the medication, there was a significant reduction in major adverse cardiovascular events (MACE = CV death, nonfatal MI or nonfatal stroke) (HR: 0.86 (CI] 95%: 0.74-0.99), and a surprising reduction in hospitalization for heart failure (HHF) (HR: 0.65 (95% CI: 0.50-0.85). The CANVAS-Program (Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes) trial, published in 2017, assessed canagliflozin in patients with DM2 at high risk for cardiovascular events receiving standard treatment. There was a reduction in combined primary outcomes (MACE = CV death, nonfatal MI or nonfatal stroke) and a 33% reduction in HHF (HR = 0.67, 95% CI: 0.52-0.87) as well as combined renal events.100 The DECLARE-TIMI 58 (Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes) trial assessed dapagliflozin in patients with DM2 and atherosclerotic disease or multiple risk factors for atherosclerotic disease receiving standard treatment. There was no reduction in the combined primary endpoint (MACE = CV death, myocardial infarction or stroke). There was a 17 percent reduction in the combined endpoint of cardiovascular death and HHF, and 27 percent (HR: 0.73 (95% CI 0.61-0.88) for HHF.101 Recently, the VERTIS-CV (Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes) trial assessed the use of ertugliflozin (not yet commercially available in Brazil) for patients with DM2, established cardiovascular disease, and receiving standard treatment. There was no reduction in the combined primary endpoint (MACE = CV death, myocardial infarction or stroke). However, a 30% decrease in HHF was observed.100 As a whole, the available data show the efficacy of SGLT2i in reducing the incidence of HF in groups of patients with DM2.102

DM2: type 2 diabetes mellitus; HHF: hospitalization for heart failure; MI: myocardial infarction; SGLT2i: sodium-glucose cotransporter-2 inhibitors.