SGLT‑2 Inhibitors Reduce Cardiovascular Events and Slow Kidney Disease Progression in Adults with Type 2 Diabetes and Atherosclerotic Cardiovascular Risk

Agent‑Specific Cardiovascular Benefits

Empagliflozin is strongly recommended for adults with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) to lower heart‑failure hospitalization and cardiovascular death. Strong recommendation. 1
In the EMPA‑REG OUTCOME trial, empagliflozin reduced heart‑failure hospitalization by 33 % compared with placebo. High‑quality evidence. 4
Dapagliflozin is strongly recommended for adults with type 2 diabetes and ASCVD, with particular benefit in patients > 50 years who have additional cardiovascular risk factors. Strong recommendation. 1
In patients with chronic kidney disease, dapagliflozin lowered all‑cause mortality by 31 % (hazard ratio 0.69). High‑quality evidence. 2
Canagliflozin is strongly recommended for adults with type 2 diabetes and ASCVD and is especially effective in those with albuminuric renal disease, reducing heart‑failure hospitalization by 33 %. Strong recommendation. 1

Empagliflozin can be initiated when estimated glomerular filtration rate (eGFR) is ≥ 20 mL/min/1.73 m². 1
Dapagliflozin may be started at eGFR ≥ 25 mL/min/1.73 m² and can be continued at lower eGFR values once therapy is established. 5
Canagliflozin is approved for use down to eGFR 30 mL/min/1.73 m² for diabetic kidney disease. 6

eGFR ≥ 30 mL/min/1.73 m² – all three agents (empagliflozin, dapagliflozin, canagliflozin) are appropriate. 1
eGFR 25–29 mL/min/1.73 m² – dapagliflozin is the preferred choice. 2
eGFR 20–24 mL/min/1.73 m² – empagliflozin or dapagliflozin may be used (limited data). 1

Heart‑failure with reduced ejection fraction – dapagliflozin or empagliflozin are strongly preferred. 1
Albuminuric kidney disease – canagliflozin or dapagliflozin are preferred. 1
General ASCVD – any of the three agents may be used. 1

Canagliflozin should be avoided in patients with a history of amputation, severe peripheral arterial disease, active diabetic foot ulcers, or osteoporosis. 6
All SGLT‑2 inhibitors are contraindicated in type 1 diabetes and in individuals with recurrent diabetic ketoacidosis. 1

Prior to starting therapy, reduce sulfonylurea dose by ≈ 50 % or insulin dose by ≈ 20 % when HbA1c is well‑controlled or hypoglycemia risk is present. 6
Assess volume status; consider lowering diuretic dose if the patient shows signs of dehydration. 6
Counsel patients that genital mycotic infections occur in 10–15 % of women; these are usually managed with topical antifungals without stopping the SGLT‑2 inhibitor. 1
Expect a temporary eGFR decline of up to 15 %, typically resolving within 1–3 months after initiation. 1
Monitor renal function and electrolytes closely during the first 4 weeks, especially in patients also receiving insulin or sulfonylureas. 6
The risk of hypoglycemia is low unless the SGLT‑2 inhibitor is combined with insulin or secretagogues. 1

Do not delay initiation of an SGLT‑2 inhibitor while awaiting “optimal” background therapy; early use yields significant residual cardiovascular risk reduction. 1
Do not discontinue the drug solely for a transient eGFR dip unless acute kidney injury is suspected; continuation at lower eGFR is safe. 1
Do not prescribe any SGLT‑2 inhibitor to patients with type 1 diabetes (absolute contraindication). 1
Do not overlook sick‑day management; advise patients to hold the medication during acute illness with reduced oral intake. 1