SGLT2 Inhibitors for Type 2 Diabetes Management

Introduction to SGLT2 Inhibitors

The American College of Cardiology recommends SGLT2 inhibitors as first-line therapy for patients with type 2 diabetes who have established cardiovascular disease, heart failure, or chronic kidney disease due to their proven benefits in reducing cardiovascular and renal outcomes 1, 2, 3

The American College of Cardiology recommends Canagliflozin 100 mg PO daily (can increase to 300 mg daily for glycemic control if eGFR ≥60 mL/min/1.73 m²) 1, 4
The American College of Cardiology recommends Dapagliflozin starting dose 5 mg PO daily for glycemic control (can increase to 10 mg daily); 10 mg PO daily for heart failure and kidney disease indications 1
The American College of Cardiology recommends Empagliflozin 10 mg PO daily (can increase to 25 mg daily for additional glycemic control) 1, 4
Canagliflozin is indicated to improve glycemic control in adults with type 2 diabetes as adjunct to diet and exercise 1
Canagliflozin is indicated to reduce risk of MI, stroke, or CV death in adults with type 2 diabetes and CV disease 1
Canagliflozin is indicated to reduce risk of end-stage kidney disease, doubling of serum creatinine, CV death, and hospitalization for heart failure in patients with type 2 diabetes and diabetic nephropathy with albuminuria 1, 5
Empagliflozin is indicated to improve glycemic control in adults with type 2 diabetes as adjunct to diet and exercise 1
Empagliflozin is indicated to reduce risk of CV death in adults with type 2 diabetes and established CV disease 1, 4

For patients with eGFR 30-59 mL/min/1.73 m², the maximum dose of Canagliflozin is 100 mg daily 1, 2
For patients with eGFR <30 mL/min/1.73 m², Canagliflozin is not recommended for glycemic control; may continue 100 mg daily if tolerated for kidney and CV benefit until dialysis 1, 2
For patients with eGFR <45 mL/min/1.73 m², Empagliflozin is not recommended for glycemic control 1, 4

History of serious hypersensitivity reaction to the specific SGLT2 inhibitor is a contraindication 1
Pregnancy or breastfeeding is a contraindication 1
Patients on dialysis (for Empagliflozin) is a contraindication 1
Discontinue SGLT2 inhibitors at least 3 days before planned surgery to prevent postoperative ketoacidosis 1
Consider pausing SGLT2 inhibitors during periods of acute illness or stressors 2

Risk of euglycemic ketoacidosis (minimal to no elevation in blood glucose) is increased with SGLT2 inhibitors 1, 2
Higher risk of diabetic ketoacidosis in patients with type 2 diabetes requiring insulin 2
Consider blood or urine ketone monitoring for detection of diabetic ketoacidosis 2
Discontinue SGLT2 inhibitor and seek immediate medical attention if ketoacidosis is suspected 2
Increased risk of genital mycotic infections compared to placebo (6% vs. 1%), higher in women than men 2
Daily hygienic measures may reduce risk of genital mycotic infections 2
Most genital mycotic infections are easily treated, but severe cases of Fournier gangrene have been reported 2
Urinary tract infections are a potential adverse effect of SGLT2 inhibitors 1
Lower limb ulcerations and soft tissue infections are potential adverse effects of SGLT2 inhibitors 1
Possible increased risk of bone fractures (particularly with Canagliflozin) 1

Glucose-lowering efficacy of SGLT2 inhibitors decreases as renal function declines, but cardiovascular and kidney benefits are preserved at lower eGFR levels 2, 6
SGLT2 inhibitors have demonstrated significant reductions in major adverse cardiovascular events, hospitalization for heart failure, and progression of kidney disease in multiple large randomized controlled trials 3, 4, 5
For cardiovascular risk reduction, SGLT2 inhibitors can be used independent of A1C levels and independent of metformin use 3