Glucose-Lowering Agents Developed in the Last Two Decades and Their Perioperative Implications

The last two decades have provided far more options f both patients and their physicians in the treatment of diabetes mellitus. While dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been approved for nearly two decades, sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are relatively new. Of interest to perioperative physicians, these drugs present specific perioperative concerns, prompting many societies to issue guidelines. Retained gastric contents due to slow gastric emptying is a significant drawback of GLP-1RAs, increasing the risk of aspiration. Recommendations include withholding GLP-1RAs for a predefined period of time, performing gastric ultrasound to evaluate gastric contents, modifying anesthesia management, particularly with regard to the airway, or canceling the scheduled (elective) surgery or procedure. SGLT-2is are known to increase the risk of euglycemic ketoacidosis. The benefits of both GLP-1RAs and SGLT-2is extend beyond the treatment of diabetes. As a result, perioperative physicians may encounter their use outside of their traditional indications. SGLT-2is are being used extensively to treat heart failure and obesity, for example. There have been other developments as well. For instance, Imeglimin, a variant of metformin available in Japan and India, Icodec, a once-weekly basal insulin formulation, and IcoSema, a once-weekly combination of Icodec plus semaglutide, are all being explored, although in their early stages or facing approval challenges.