Role of SGLT2 Inhibitors in Type 2 Diabetes with Cardiovascular Disease
SGLT2 inhibitors should be considered first-line therapy for patients with type 2 diabetes who have established atherosclerotic cardiovascular disease (ASCVD), multiple ASCVD risk factors, or diabetic kidney disease to reduce major adverse cardiovascular events, heart failure hospitalization, and mortality. 1, 2
Patient Selection for SGLT2 Inhibitors
SGLT2 inhibitors provide significant benefits beyond glycemic control, particularly in high-risk populations:
- Established ASCVD: Patients with established cardiovascular disease should receive an SGLT2 inhibitor to reduce major adverse cardiovascular events (MACE) 1
- Heart Failure: Particularly beneficial in patients with heart failure with preserved or reduced ejection fraction 2
- Chronic Kidney Disease: Recommended for patients with CKD if eGFR ≥30 mL/min/1.73m² to prevent progression of kidney disease, especially with albuminuria 2
Cardiovascular Benefits
The cardiovascular benefits of SGLT2 inhibitors are well-documented in major clinical trials:
- Empagliflozin: Reduced the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease 3
- Canagliflozin: Reduces the risk of major adverse cardiovascular events, end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure 4
- Dapagliflozin: Demonstrated cardiovascular benefits including reduced MACE in adults with type 2 diabetes and established cardiovascular disease 2
Mechanism of Cardiovascular Protection
The cardiovascular benefits of SGLT2 inhibitors appear to be mediated through multiple mechanisms:
- Hemodynamic effects through osmotic diuresis and natriuresis 5
- Improved glomerular hemodynamic function 6
- Reduced blood pressure and body weight 7
- Decreased inflammation and lipid peroxidation 8
Practical Considerations for Initiation and Monitoring
When starting an SGLT2 inhibitor, consider the following:
- Hypoglycemia risk: If A1C is well-controlled at baseline, reduce dose of sulfonylurea by 50% or basal insulin by 20% 1
- Volume status: May need to reduce diuretic doses; monitor for symptoms of hypotension 1
- Ketoacidosis risk: Educate patients about symptoms (nausea, vomiting, weakness) and that ketoacidosis can occur even with blood glucose in the 150-250 mg/dL range 1
- Genital mycotic infections: Educate patients about this potential side effect 1
- Renal function: Monitor kidney function; discontinue if eGFR falls persistently below 45 mL/min/1.73m² 3
Special Precautions
- Foot care: Particular caution with canagliflozin in patients with history of amputation, severe peripheral arterial disease, neuropathy, or diabetic foot ulcers 1
- Osteoporosis: Consider avoiding canagliflozin in patients with osteoporosis 1
- Contraindications: Avoid in patients with history of diabetic ketoacidosis, severe renal impairment (eGFR <30 mL/min/1.73m²), or end-stage renal disease 3, 4
Algorithm for SGLT2 Inhibitor Selection
For patients with established ASCVD or multiple risk factors:
- Start with an SGLT2 inhibitor with proven cardiovascular benefit (empagliflozin, canagliflozin, dapagliflozin)
For patients with heart failure:
- SGLT2 inhibitors are strongly recommended to reduce risk of worsening heart failure and cardiovascular death
For patients with CKD:
- Use SGLT2 inhibitor if eGFR ≥30 mL/min/1.73m², particularly with albuminuria
For patients with multiple indications:
- Choose agent based on specific evidence for the predominant condition
- Consider empagliflozin for patients with osteoporosis or amputation risk
SGLT2 inhibitors have transformed the clinical care of type 2 diabetes by providing benefits that extend well beyond glycemic control, making them essential components of treatment for patients with cardiovascular disease.