SGLT2 Inhibitor-Associated Ketoacidosis Complicated by Semaglutide or Cardiac Surgery Requires Vigilant ICU Management

Type 2 diabetes (T2D) management has evolved to include agents like SGLT2 inhibitors (SGLT2i), which offer cardiovascular and renal benefits beyond glycemic control. However, SGLT2i use carries a risk of diabetic ketoacidosis (DKA), a severe complication, particularly in critically ill patients. A significant diagnostic challenge arises because SGLT2i-associated DKA often presents as euglycemic DKA, with plasma glucose levels below the typical DKA threshold, leading to delayed recognition and management in the intensive care unit (ICU). This gap highlights the need for improved awareness and protocols.

This report details two case studies of male patients with Type 2 diabetes who developed SGLT2i-associated ketoacidosis under different stressors. The first patient experienced DKA following coronary artery bypass graft (CABG) surgery. The second patient developed DKA after semaglutide was added to his existing therapeutic regimen. Both cases involved presentation with high anion gap metabolic acidosis, ketonuria, and plasma glucose levels < 200 mg/dL. Management for both patients required intravenous insulin protocols and glucose supplementation to reverse the ketotic state.

The two presented cases underscore critical diagnostic and management pitfalls of SGLT2i-associated ketoacidosis in the ICU. > Both patients, despite having Type 2 diabetes and being on SGLT2i, developed DKA with plasma glucose levels < 200 mg/dL, a key feature of euglycemic DKA that can delay diagnosis. The first patient developed DKA post-CABG surgery, indicating surgical stress as a potential trigger. The second patient developed DKA after the addition of semaglutide, a GLP-1R agonist, to his regimen, suggesting a potential interaction or additive risk factor. In both instances, the patients exhibited high anion gap metabolic acidosis and ketonuria. Effective management consistently required aggressive intravenous insulin protocols combined with glucose supplementation to successfully resolve the ketosis. These cases highlight the importance of recognizing atypical DKA presentations.