Advances in Cardiovascular Pharmacotherapy. IV. Sodium-Glucose Cotransporter Type 2 Inhibitors, Part 2: Mechanisms...

This second part of a two-part review on the cardiovascular pharmacology of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) describes the mechanisms that have been proposed to explain how these drugs improve outcomes in heart failure and myocardial infarction and discusses their adverse effects and perioperative implications for patients with or without diabetes undergoing major surgery. The mechanism(s) by which SGLT2i exert beneficial cardiovascular actions are incompletely understood at present, but they are most likely multifactorial in origin, as no single factor has been proven definitive when considered alone. SGLT2i increase the risk of genital mycotic infections and diabetic ketoacidosis (DKA) in patients with diabetes, but the drugs do not cause severe hypoglycemia requiring intervention, urinary tract infection, hypovolemia, or acute kidney injury, among other postulated adverse outcomes. Perioperative euglycemic DKA (euDKA) is rare, but vigilance for its occurrence is required when an anion gap metabolic acidosis develops despite normal or only modestly elevated glucose concentration. Current guidelines recommend withholding SGLT2i for at least 48 hours to minimize the risk of DKA before elective major surgery in patients with but not without diabetes. The guidelines further emphasize the need to maintain a high index of suspicion for DKA and euDKA when SGLT2i therapy cannot be stopped because of urgent or emergent surgery so that appropriate treatment can be promptly initiated to prevent morbidity and mortality.