Cardiovascular Benefits of SGLT2 Inhibitors

Introduction to SGLT2 Inhibitor Benefits

The American Heart Association acknowledges that empagliflozin demonstrates significant cardiovascular benefits in patients with type 2 diabetes and established cardiovascular disease, including a 14% reduction in major adverse cardiovascular events (MACE), 38% reduction in cardiovascular mortality, 35% reduction in heart failure hospitalizations, and 32% reduction in all-cause mortality 1
The American College of Cardiology and the American Diabetes Association recommend initiating SGLT2 inhibitors in patients with type 2 diabetes and established cardiovascular disease to reduce the risk of cardiovascular death, heart failure hospitalizations, and improve survival 2, 3, 4, 5, 6

Empagliflozin shows a 39% reduction in progression of chronic kidney disease, with benefits observed regardless of baseline glycemic control or blood sugar levels 1
SGLT2 inhibitors are recommended for patients with type 2 diabetes and chronic kidney disease (eGFR ≥45 mL/min/1.73 m²) to reduce the risk of cardiovascular death, heart failure hospitalizations, and improve survival 2, 3, 4, 5, 6

Patients with acute myocardial infarction and type 2 diabetes should be initiated on SGLT2 inhibitors when clinically stable before discharge 2, 7
The American College of Cardiology recommends SGLT2 inhibitors for all patients with heart failure, regardless of ejection fraction, as they significantly reduce cardiovascular mortality and heart failure hospitalizations across the spectrum of heart failure 4, 8
GLP-1 receptor agonists may be considered for DM treatment in patients with heart failure (Class IIb recommendation), and are recommended as alternative if SGLT2 inhibitor contraindicated by the American College of Cardiology 9, 10, 11

The recommended dosage for SGLT2 inhibitors is 10 mg PO daily for empagliflozin (Jardiance) and dapagliflozin, and 100 mg PO daily for canagliflozin 3
Consider reducing diuretic dose if patient is on diuretic therapy to prevent volume depletion 3

Contraindications for SGLT2 inhibitors include history of serious hypersensitivity to the drug, pregnancy or breastfeeding, type 1 diabetes, severe renal impairment (eGFR <30 mL/min/1.73 m²), and end-stage renal disease or dialysis 3, 12, 8
Precautions include discontinuing at least 3 days before planned surgery to prevent postoperative ketoacidosis, and using with caution in patients with prior amputation, severe peripheral neuropathy, or peripheral vascular disease 3, 13, 12

Monitor renal function, signs of genital mycotic infections, volume status, symptoms of diabetic ketoacidosis, and lower limb ulcerations in patients on SGLT2 inhibitors 3, 12, 4, 8, 7
Common adverse effects of SGLT2 inhibitors include genital mycotic infections, urinary tract infections, and volume depletion, particularly in elderly patients or those on diuretics 12
Rare but serious adverse effects include euglycemic diabetic ketoacidosis, bone fractures, and lower limb amputations, especially with canagliflozin in patients with peripheral vascular disease 12

SGLT2 inhibitors are relatively expensive compared to older diabetes medications, with median monthly AWP ranging from $354-$627, although prices vary by medication and dosage 16
In-hospital initiation of SGLT2 inhibitors improves post-discharge medication adherence and reduces early post-discharge events, with failure to initiate SGLT2 inhibitors during hospitalization resulting in >75% chance of therapy never being started within the next year 7
The European Society of Cardiology recommends SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiovascular benefit in patients with type 2 diabetes and peripheral artery disease to reduce cardiovascular events, independent of baseline or target HbA1c and concomitant glucose-lowering medication (Class I, Level A recommendation) 11