Role of SGLT2 Inhibitors in Type 2 Diabetes with Cardiovascular Disease
SGLT2 inhibitors should be prescribed for all patients with type 2 diabetes who have established atherosclerotic cardiovascular disease (ASCVD), multiple ASCVD risk factors, or chronic kidney disease to reduce major adverse cardiovascular events, heart failure hospitalization, and mortality. 1
Patient Selection and Indications
SGLT2 inhibitors provide significant cardiovascular and renal benefits that extend beyond glycemic control. The American Diabetes Association strongly recommends their use in specific high-risk populations:
Primary Indications (Class A Evidence):
- Established ASCVD: Reduces major adverse cardiovascular events (MACE) 1
- Heart Failure: Particularly beneficial in heart failure with either preserved or reduced ejection fraction 1
- Reduces risk of worsening heart failure and cardiovascular death
- Improves symptoms, physical limitations, and quality of life
- Chronic Kidney Disease: Prevents progression of CKD, especially with albuminuria 1
Additional Benefits:
- Blood pressure reduction
- Weight loss
- Improved lipid profile
- Reduced arterial stiffness 2
Treatment Algorithm
Assess cardiovascular and renal risk:
- Check for established ASCVD (prior MI, stroke, unstable angina, revascularization)
- Evaluate for heart failure (especially with reduced ejection fraction)
- Screen for CKD (eGFR and albuminuria)
Initiate SGLT2 inhibitor if any of these conditions are present:
Select appropriate SGLT2 inhibitor:
- Empagliflozin: FDA-approved to reduce cardiovascular death in adults with T2DM and established cardiovascular disease 4
- Canagliflozin: FDA-approved to reduce MACE in adults with T2DM and established cardiovascular disease; also approved to reduce risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with T2DM and diabetic nephropathy with albuminuria 5
- Dapagliflozin: Demonstrated cardiovascular benefits in clinical trials 1
Monitoring and Precautions
Before Initiating:
- Assess renal function (do not initiate if eGFR <45 mL/min/1.73m² for empagliflozin) 4
- Evaluate volume status, especially in elderly patients or those on diuretics 4
- Consider risk of genital mycotic infections and urinary tract infections 4
Common Side Effects to Monitor:
- Genital mycotic infections (most common adverse event) 4
- Urinary tract infections 4
- Volume depletion, especially in elderly patients 4
- Risk of euglycemic diabetic ketoacidosis 6
Important Cautions:
- Use with caution in patients with foot ulcers or at high risk for amputation 1
- May need to reduce dose of insulin or sulfonylureas when used in combination to prevent hypoglycemia 7
- Discontinue if eGFR falls persistently below 45 mL/min/1.73m² 4
Evidence Quality and Considerations
The recommendation for SGLT2 inhibitors in cardiovascular risk reduction is supported by multiple large randomized controlled trials showing significant reductions in cardiovascular events 1. Meta-analyses confirm that SGLT2 inhibitors reduce the risk of MACE, heart failure hospitalization, and progression of kidney disease 1.
The American Diabetes Association's 2025 Standards of Care provides the strongest and most recent evidence supporting SGLT2 inhibitors for cardiovascular risk reduction, with a Grade A recommendation for their use in patients with established ASCVD, heart failure, or CKD 1.
While both SGLT2 inhibitors and GLP-1 receptor agonists show cardiovascular benefits, SGLT2 inhibitors have more robust evidence for heart failure and kidney disease outcomes 1, 8.