Should an SGLT2 Inhibitor Be Added to This Patient's Regimen?
Yes, add an SGLT2 inhibitor with proven cardiovascular benefit (empagliflozin or dapagliflozin) to this patient's current regimen of metformin and glipizide, even though the HbA1c is at goal, because the cardiovascular and renal benefits of SGLT2 inhibitors are independent of baseline A1C or glycemic control. 1
Rationale for Adding SGLT2 Inhibitor Despite Controlled A1C
The 2024 ADA Standards of Care explicitly state that SGLT2 inhibitors or GLP-1 receptor agonists can be initiated in people with type 2 diabetes and cardiovascular disease independent of the current A1C or A1C goal or metformin therapy. 1 The cardiovascular benefits are not contingent upon A1C lowering—these agents provide mortality reduction, cardiovascular event reduction, and renal protection through pleiotropic effects including weight loss, hemodynamic effects, blood pressure lowering, and anti-inflammatory changes. 1
Two specific strategies are recommended: 1
- If already on dual therapy (like this patient on metformin + glipizide) and not on an SGLT2 inhibitor or GLP-1 receptor agonist, consider switching to one of these agents with proven cardiovascular benefit
- Introduce SGLT2 inhibitors in people with CVD at A1C goal for cardiovascular benefit, independent of baseline A1C
Addressing the Impaired Renal Function
The presence of impaired renal function requires careful consideration but does not automatically preclude SGLT2 inhibitor use. SGLT2 inhibitors provide significant renal protective benefits in patients with chronic kidney disease. 1 However, specific dosing adjustments are required:
- Empagliflozin: Can be used if eGFR ≥30 mL/min/1.73 m²; use 10 mg daily if eGFR 30-44 mL/min/1.73 m²; contraindicated if eGFR <30 mL/min/1.73 m² 2
- Dapagliflozin: Similar renal dosing considerations apply 2
The exact eGFR must be assessed before initiating therapy to determine appropriate dosing or contraindications.
Managing the Sulfonylurea (Glipizide)
Consider discontinuing or significantly reducing glipizide when adding the SGLT2 inhibitor. 3 Sulfonylureas carry substantial hypoglycemia risk, particularly when combined with multiple glucose-lowering agents, and provide minimal additional benefit once more effective agents are added. 3 The combination of metformin and an SGLT2 inhibitor addresses both insulin resistance and provides cardiovascular protection without the hypoglycemia risk associated with sulfonylureas. 3
Practical approach: 3
- Either discontinue glipizide completely when initiating the SGLT2 inhibitor
- Or reduce glipizide dose by 50% initially, then discontinue within 1-2 weeks as the SGLT2 inhibitor takes effect
Specific SGLT2 Inhibitor Selection
Empagliflozin is the preferred SGLT2 inhibitor based on available evidence and overall benefit-risk balance. 1 Start at 10 mg daily, which has equivalent cardiovascular benefit to the 25 mg dose. 1, 2 Empagliflozin reduced cardiovascular death by 38% and all-cause mortality by 32% in patients with established atherosclerotic cardiovascular disease. 2
Dapagliflozin is an acceptable alternative with similar cardiovascular and renal benefits. 4, 5 Studies demonstrate that dapagliflozin combined with metformin provides superior glycemic control compared to sulfonylureas, with the added benefits of weight loss rather than weight gain. 4
Monitoring and Safety Considerations
Key monitoring parameters: 2
- Assess volume depletion risk, particularly if the patient is on diuretics for hypertension
- Monitor renal function (eGFR) periodically, as both metformin and SGLT2 inhibitors require dose adjustment with declining kidney function
- Educate about genital mycotic infection risk and importance of hygiene
- Monitor for euglycemic diabetic ketoacidosis symptoms, though risk is primarily in type 1 diabetes
- Reassess HbA1c in 3 months to evaluate overall glycemic control 3
Important Caveats
Avoid canagliflozin if the patient has severe peripheral artery disease, prior amputations, or peripheral neuropathy due to increased amputation risk demonstrated in the CANVAS trial. 2 Empagliflozin showed no increased amputation risk even in patients with peripheral artery disease. 2
Continue metformin as the foundation of therapy unless contraindicated (eGFR <30 mL/min). 1, 3 Metformin provides cardiovascular benefits and reduces insulin requirements when used in combination therapy. 3
The rare but serious risk of metabolic acidosis with the combination of metformin and SGLT2 inhibitors should be considered, though this remains uncommon. 6