Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the perioperative setting

Excerpt

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are the newest class of oral antihyperglycemic agents approved for treating type 2 diabetes mellitus (T2DM). Mechanistically, SGLT-2i reduce blood glucose by promoting glucosuria through inhibition of sodium-glucose co-transporter-2 (SGLT-2) channels in the epithelium of the renal proximal tubules. SGLT-2i modestly reduce blood glucose concentrations (HbA1c ~ −0.7 to −1.0%),1 with glucoregulatory effects that occur independent of insulin secretion; hence, they are associated with a low risk of hypoglycemia relative to insulin secretory agents.2 In light of their favourable benefit-to-risk profile, ease of use (once daily oral administration), and ancillary benefits on total body weight loss (~3 kg) and blood pressure (BP) reduction (systolic BP -4 to -6 mmHg, diastolic BP −1 to −2 mmHg), SGLT-2i are now routinely used in practice. Some agents in this drug class are now prioritized (e.g., empagliflozin) as preferred second line therapy in patients with clinical cardiovascular disease, after metformin.1,3 These recommendations followed the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial, a cardiovascular safety study in (T2DM) patients with established clinical cardiovascular disease.4 Empagliflozin significantly reduced the risk of cardiovascular mortality (38%), hospitalization for heart failure (35%),4 and nephropathy events (39%).5 The combined results of two more recent cardiovascular safety studies with the SGLT-2i, canagliflozin (CANagliflozin cardioVascular Assessment Study [CANVAS] and CANagliflozin cardioVascular Assessment Study-Renal [CANVAS-R]), known collectively as the CANVAS program, were also consistent with cardiac and renal protection in a large T2DM population at high cardiovascular risk.6 In light of these clinical trial data, SGLT-2i will likely be encountered more frequently by anesthesiologists in the perioperative period.

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