Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are known to have cardioprotective effects. Their use can reduce major adverse cardiovascular events (MACE) both in patients with or without established cardiovascular disease. Euglycemic diabetic ketoacidosis (EDKA) is rare, but the advent of sodium-glucose cotransporter 2 inhibitors (SGLT2is) has been associated with an increase in its incidence. The most common side effects of GLP-1RAs are gastrointestinal, mainly nausea, but also vomiting and diarrhea. Dehydration is a precipitating factor of diabetic ketoacidosis (DKA). It is possible that the concomitant treatment with an SGLT2i and a GLP1-RA increases the risk of EDKA. We present a case series of that. Case Reports: Case 1: A 43-year-old woman with with a history of DM2 and hypertension was found to have EDKA after presenting with worsening of nausea and vomiting associated with a recent increase in the dose of tirzepatide. Her other DM2 medications included metformin, empagliflozin and insulin. She had a history of one prior DKA episode. Case 2: A 57-year-old man with a history of DM2, hypertension and hyperlipidemia was found to have EDKA after presenting with nausea and vomiting associated with a recent increase in the dose of dulaglutide. His other DM2 medications were metformin and empagliflozin. He had a history of a prior DKA episode. Case 3: A 65-year-old woman with a history of DM2 was found to have EDKA after presenting with nausea and vomiting associated with a recent initiation of semaglutide. Her other DM2 medications were metformin, empagliflozin and insulin. She had a history of a prior DKA episode. Discussion: All 3 patients had a temporal association between initiation or increasing the dose of the GLP-1RA and GI symptoms of nausea and vomiting that preceded EDKA. All 3 patients had uncontrolled diabetes mellitus (DM), and had a history of prior DKA. As both GLP-1RAs and SLGT2is are cardioprotective medications, it is important to identify the risk factors for DKA to guide the decision to treat patients who have them properly to minimize the possibility of this complication. Conclusion: Awareness of side effects of GLP-1RAs and SGLTis is key in attempting to minimize complications. It is important to identify patients at risk for EDKA, and to focus on educating patients on seeking medical care promptly should these side effects or concerns for EDKA develop.
Ibrahim Youssef (Tue,) studied this question.
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