Intensification With SGLT2 Inhibitors for Type 2 Diabetes
An A1c of 9.5% is above the usual individualized glycemic goal for many nonpregnant adults, which is an A1c <7% when safe. [1] For adults with type 2 diabetes with A1c ≥1.5% above the individualized goal, initial combination pharmacotherapy is recommended. [2] SGLT2 inhibitors are appropriate add-on options to existing sulfonylurea therapy when metformin is refused. [2]
Appropriate SGLT2 Inhibitors (Agent Options)
The following SGLT2 inhibitors are listed as options in the ADA pharmacologic treatment framework: [3]
- Canagliflozin [3]
- Empagliflozin [3]
- Dapagliflozin [3]
- Ertugliflozin [3]
Medication Selection Algorithm
For glycemic management in combination with a sulfonylurea, SGLT2 inhibitor selection should be aligned with the patient’s renal function and comorbidity priorities. [2] SGLT2 inhibitors should be used for cardiovascular and kidney risk management in appropriate patients irrespective of A1c. [4] When SGLT2 inhibitor benefits for CKD or cardiovascular risk are prioritized, continuing or initiating SGLT2 inhibitor therapy is recommended when eGFR is above the label-specified threshold (ADA practice point uses an eGFR >20 mL/min/1.73 m2 threshold for cardiovascular and kidney benefit). [3]
Monotherapy Versus Combination Therapy
Combination therapy is recommended when A1c is ≥1.5% above the individualized goal. [2] Adding an SGLT2 inhibitor to a sulfonylurea constitutes combination therapy. [2]
Treatment Initiation Thresholds and Practical Constraints
An SGLT2 inhibitor can be started for cardiovascular and kidney benefit when eGFR is ≥20 mL/min/1.73 m2. [3] The glucose-lowering effect is reduced at eGFR <45 mL/min/1.73 m2, but cardiovascular and kidney benefit may persist. [3]
Hypoglycemia and Weight Considerations
SGLT2 inhibitors are characterized by no hypoglycemia risk when used without insulin or insulin secretagogues. [3] Weight effects are expected to be weight loss (intermediate) with SGLT2 inhibitors. [3]
Common Pitfalls to Avoid
SGLT2 inhibitors should be discontinued in settings that increase risk for diabetic ketoacidosis, including perioperative periods and critical illness or prolonged fasting. [3] Sick-day planning should be used to reduce euglycemic diabetic ketoacidosis risk in predisposed individuals. [3] Genital mycotic infections should be prevented with genital hygiene strategies and avoidance in high-risk individuals when applicable. [3]
Target Blood Pressure
Not applicable to SGLT2 inhibitor selection based on the provided data (no blood pressure target information provided). [1]
Glycemic Goal Targets
A reasonable A1c goal for many nonpregnant adults is <7%. [1] An A1c of 9.5% meets the ADA threshold for recommending treatment intensification with combination pharmacotherapy because it is likely ≥1.5% above the individualized goal. [1,2]
Medication Recommendation Summary
An SGLT2 inhibitor (canagliflozin, empagliflozin, dapagliflozin, or ertugliflozin) is an appropriate add-on to current glipizide extended-release when metformin is refused. [2,3] SGLT2 inhibitor selection should incorporate kidney function for dosing feasibility and retention of kidney/cardiovascular benefits, using an eGFR ≥20 mL/min/1.73 m2 threshold for cardiovascular and kidney benefit in ADA practice guidance. [3]