Perioperative Considerations for the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes

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Oral antihyperglycemic agents traditionally target restoring β-cell function, increasing insulin secretion, restoring insulin sensitivity, and promoting tissue glucose uptake for treating type 2 diabetes. A newer class of oral antihyperglycemic agents, called sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2is), frequently referred to as “gliflozins” or “glucoretics,” reduce blood glucose by promoting urinary glucose excretion through inhibiting SGLT2 channels located on the luminal side of the renal proximal tubules (Figure).1 In patients with type 2 diabetes, SGLT2is reduce the reabsorption of the filtered urinary glucose load by ~50%. This translates into an absolute reduction in hemoglobin A1c (HbA1c) (%) by −0.5 to −0.8.1 These drugs are currently not indicated for use in patients with type 1 diabetes.
Unlike conventional blood glucose–lowering agents, such as sulfonylureas, the glucoregulatory effects of SGLT2i are independent of insulin secretion, resulting in a low risk for hypoglycemia.2,3 Part of the attraction of using SGLT2is in type 2 diabetes is the associated body weight loss (approximately −2 to −3 kg) due to the negative energy balance from the daily caloric losses associated with glycosuria.2 With moderate glycemic lowering, favorable patient tolerability and safety profiles, and once-daily oral administration, these drugs are now increasingly used in the routine management of type 2 diabetes. Moreover, in the recent EMPA-REG OUTCOME trial,4 a safety study for the SGLT2i empagliflozin looking at cardiovascular (CV) outcomes and mortality in type 2 diabetes, there was a significant reduction in mortality (relative risk reduction [RRR], 32%; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.57–0.82, P < .001), lowered rates of hospitalization for heart failure (RRR, 35%; HR, 0.65; 95% CI, 0.50–0.85; P = .002), and attenuated nephropathy events (RRR, 39%; HR, 0.61; 95% CI, 0.55–0.69, P < .001)5 in patients with type 2 diabetes and CV disease. These results have already had an impact on management algorithms for type 2 diabetes patients with clinical CV disease, and have led to regulatory changes around the use of empagliflozin as a CV protective therapy.6 This is likely to culminate in anesthesiologists encountering these drugs more frequently.
This raises important questions around specific clinical considerations for the use of SGLT2is during the perioperative period. Despite extensive literature searches in Embase, MEDLINE, and PubMed using the keywords sodium-glucose transporter 2 inhibitors, anesthesia, type 2 diabetes, and diabetic ketoacidosis (DKA), we found a paucity of manuscripts addressing this aspect of clinical care.
While generally well tolerated, clinicians should be aware of class-wide safety precautions for SGLT2i use. The most common adverse effects are urinary tract and genital infections due to increased glycosuria, especially with mycotic infections from candida species.1 In this commentary, we review the nonglycemic effects of SGLT2is and underscore the potential for adverse effects that may occur during the perioperative period. These include specific prescribing indications for SGLT2i use in patients with type 2 diabetes with renal function impairment, and potential adverse effects, including hemodynamic consequence and metabolic effects. Finally, we provide specific suggestions for the perioperative management of patients taking SGLT2is who are undergoing surgery.

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