Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors and Glucagon-Like Peptide-1 (GLP-1) Analogs

Educational Objectives

The goal of this program is to improve the perioperative management of patients on sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) analogs. After hearing and assimilating this program, the clinician will be better able to:

1. Identify the adverse effects of SGLT-2 inhibitors.
2. Implement the American Society of Anesthesiologists Consensus-based guidelines on the preoperative management of patients on GLP-1 analogs.

Summary

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors

Indications: include type 2 diabetes mellitus (T2DM), heart failure with reduced ejection fraction, and nondiabetic kidney disease; use of SGLT-2 inhibitors is increasing because of cardiovascular and kidney benefits

Adverse effects (AEs)

Euglycemic diabetic ketoacidosis (EDKA): a rare but serious complication of SGLT-2 inhibitors; blood glucose level is 100 to 180 mg/Dl; patients are usually critically ill, have undergone gastric bypass surgery (reduced reserve), on nothing by mouth (NBM) or prolonged NBM, on catecholamines, or have undergone major surgeries; if EDKA is suspected, test for ketones; treatment — provide insulin plus dextrose to prevent hypoglycemia

Dehydration: SGLT-2 inhibitors cause glucosuria (release glucose in the urine) and increased urine volume; patients may be critically ill, have nausea and vomiting, or are undergoing preoperative preparation and may be more dehydrated than expected; intraoperatively, a decrease in preload and hypotension may occur; patients may not appear hypovolemic clinically

Preoperative management: many European societies recommend continuing SGLT-2 inhibitors, with a high suspicion for EDKA perioperatively, as the risk for EDKA is low; the US Food and Drug Administration recommends discontinuation of SGLT-2 inhibitors (eg, empagliflozin) 3 days before surgery

Glucagon-Like Peptide-1 (GLP-1) Analogs

Indications: include T2DM and weight loss (body mass index [BMI] >30 or BMI >27 with obesity-related complications); patients in weight loss clinics may be on GLP-1 analogs (even when not clinically indicated) and may not report it on their medication list; inquire about use of GLP-1 analogs during preoperative assessment

Benefits: include glycemic control, weight loss, reduced cardiovascular mortality, and reduced risk for stroke

Adverse effects: gastrointestinal (GI) Aes include nausea, vomiting, gastroparesis, diarrhea, and constipation; gastroparesis may occur during the initiation of GLP-1 analogs (usually resolves after 8-12 wk); GI Aes would have resolved in patients who were initiated on GLP-1 analogs >6 mo prior; patients may present with gallbladder disease from the rapid weight loss

Anesthetic implications: patients on GLP-1 analogs are at increased risk for aspiration (may be related to gastroparesis); preoperative assessment is vital; patients with gastroparesis may have residual gastric contents (RGC; data on the volume of RGC leading to aspiration unclear); no increased risk for postoperative nausea or vomiting; small studies and case reports indicate that patients with GI symptoms are at increased risk for RGC

The American Society of Anesthesiologists (ASA) consensus recommendations (for elective procedures): for patients with GI symptoms, reschedule or proceed with “full stomach” precautions (risk for aspiration is high); for patients with no GI symptoms when GLP-1 analogs are withheld as advised, proceed as usual; for patients with no GI symptoms when GLP-1 analogs are not withheld, proceed with full stomach precautions or consider gastric ultrasonography (GUS); if the stomach appears empty on GUS, proceed as usual; if the stomach is full on GUS or inconclusive, reschedule or proceed with full stomach precautions

Gastric ultrasonography: the curvilinear probe is placed in the subxiphoid area, with the indicator pointed cephalad; structures that can be visualized include liver, antrum of the stomach, pancreas, superior mesenteric artery, aorta, and inferior vena cava; solid contents in stomach — significant hyperechoic material can be seen; gastric air appears as shadowing; fluid in stomach — no consensus on the amount of fluid that causes aspiration; ≈1.5 Ml/kg fluid is expected in an empty stomach; the volume of the liquid can be calculated by multiplying the cross-sectional area of the antrum by the patient’s age (to assess whether the stomach is full)

Discontinuing GLP-1 analogs before surgery: ASA recommendations — for patients on daily dosing, consider holding GLP-1 analogs on the day of the procedure or surgery; for patients on weekly dosing, consider holding GLP-1 agonists 1 wk prior to the procedure or surgery (or consider holding the next dose before surgery); European and Australian societies — recommend continuing GLP-1 analogs; Society for Perioperative Assessment and Quality Improvement — recommend holding GLP-1 analogs for ≈1 wk in the presence of GI symptoms or before a bowel surgery

The half-life of GLP-1 analogs: the half-life of long-acting medications is ≈7 days; as ≈4 half-lives are required for complete elimination, the medication should be paused for ≈1 mo to allow symptoms to resolve; gastroparesis may persist even after 1 mo (may take 3-4 mo to resolve); however, if the GLP-1 analog is held for 1 mo, perioperative glycemic control becomes difficult; because the patient may require consultation with an endocrinologist or their primary care physician to start insulin, many societies recommend continuing GLP-1 agonists before surgery

GI endoscopy: a study found low incidence of aspiration during GI endoscopy in patients on GLP-1 analogs with GI symptoms; use clinical judgment on the need for intubation to prevent aspiration

Reducing aspiration risk: ASA recommends considering prokinetic agents for patients at increased risk for aspiration; data on the efficacy of H₂ blockers in patients with gastroparesis are lacking; prolonged fasting with a clear liquid diet for 24, 48, or 72 hr has been suggested

Readings

Are Serious Anesthesia Risks of Semaglutide and Other GLP-1 Agonists Under-Recognized? Case Reports of Retained Solid Gastric Contents in Patients Undergoing Anesthesia. Anesthesia Patient Safety Foundation. https://www.apsf.org/article/are-serious-anesthesia-risks-of-semaglutide-and-other-glp-1-agonists-under-recognized/; Patel K, Nair A. A literature review of the therapeutic perspectives of sodium-glucose cotransporter-2 (SGLT2) inhibitor-induced euglycemic diabetic ketoacidosis. Cureus. 2022;14(9):e29652. Published 2022 Sep 27. doi:10.7759/cureus.29652; Ushakumari DS, Sladen RN. ASA Consensus-based guidance on preoperative management of patients on glucagon-like peptide-1 receptor agonists. Anesthesiology. 2024;140(2):346-348. doi:10.1097/ALN.0000000000004776; van Zuylen ML, Siegelaar SE, Plummer MP, et al. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration. Br J Anaesth. 2024;132(4):644-648. doi:10.1016/j.bja.2024.01.001.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Freeman was recorded at the Texas Society of Anesthesiologists 2023 Annual Meeting, held September 7-10, 2023, in Round Rock, TX, and presented by the Texas Society of Anesthesiologists. For information on upcoming CME activities from this presenter, please visit tsa.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

AN663002

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.