P-26 DIABETIC KETOACIDOSIS: A POTENTIAL RISK OF SGLT2 INHIBITOR USE
Authors: Yahia Seif Eldin , Tierney Blathine , Terrance Steffy , Oyegunle Adeolu 
Published: January 2025

Abstract

Introduction
Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors have been increasingly linked to the development of ketoacidosis in individuals with presumed Type 2 Diabetes, despite the positive cardiorenal effects that have made SGLT2 inhibitors popular in managing Type 2 Diabetes. The clinical presentation of SGLT2 inhibitor-induced diabetic ketoacidosis (DKA) can be subtle, and patients may not necessarily exhibit hyperglycemia. Diagnosis can be complicated by other comorbidities, precipitating factors, and concurrent medications. Additionally, primary care clinicians may lack the means for early detection of rising blood ketone levels, and patients might inadvertently neglect the "sick day" rule.
Moreover, a study in Australia found that 21% of Type 2 Diabetes patients on SGLT2 inhibitors who developed DKA were later diagnosed with Type 1 Diabetes or LADA. This highlights the need for clinicians to maintain a high index of suspicion for SGLT2 inhibitor-related DKA, ensuring prompt referral for evaluation and careful consideration of discontinuing the medication based on clinical outcomes.

Clinical Case
We reported a case of a 72-year-old woman with a 13-year history of Type 2 Diabetes Mellitus (DM) presented to the Emergency Department with reduced oral intake, generalized weakness, shortness of breath, and worsening pedal swelling. Her medical history included diabetic neuropathy, hypertension, a prior transient ischemic attack, and osteoarthrosis. She was on multiple medications, including empagliflozin, valsartan, and metformin. On examination, the patient was tachypneic with oral thrush, sacral edema, and dry mucosa. Initial investigations showed hyperglycemia (20.4 mmol/L), acidosis (pH 7.25), high blood ketones (7.2 mmol/L), and severe hypokalemia (2.2 mmol/L), leading to a diagnosis of diabetic ketoacidosis. She was transferred to the ICU, and an elevated D-dimer (1.4 µg/mL) prompted investigation for a possible pulmonary embolism.
Further tests revealed an HbA1c of 91 mmol/mol, negative results for islet cell antibodies, GAD 65 antibodies, and C-peptide. The anti-factor Xa level was 1.19 IU/mL and antinuclear antibody specificity was normal. CT pulmonary angiography confirmed a small subsegmental pulmonary embolism. Empagliflozin was discontinued and the patient was started on Metformin, Gliclazide and Tresiba. Edoxaban was prescribed for pulmonary embolism. Upon discharge, her general practitioner was informed that she was no longer a candidate for SGLT2 inhibitors.

Conclusion
The report advises clinicians to remain alert for ketoacidosis associated with SGLT2 inhibitors in Type 2 DM patients, even when euglycemic. Emphasizing adherence to the "sick day rule" and discontinuing the medication at least four days prior to any surgery is essential. Patients who experience DKA related to SGLT2 inhibitors should be considered as inappropriate candidates for continued use of these agents.
Funding: none
No conflicts of interestFigure 1:Mechanism of action of SGLT2 inhibitorsSGLT2 inhibitors, like canagliflozin and empagliflozin, work by blocking the SGLT2 protein in the kidneys, leading to increased glucose excretion in the urine and lower blood glucose levels. They help preserve pancreatic beta-cell function, reduce stress on these cells, and slow beta-cell dysfunction. Additionally, they protect the kidneys by lowering intraglomerular pressure and albuminuria, slowing diabetic nephropathy. These inhibitors also offer cardiovascular benefits, including reduced risk of heart failure, likely due to effects on blood pressure, fluid volume, and glucose control. Furthermore, they aid in weight loss by increasing glucose excretion, which reduces body fat mass and improves metabolic health. Taken from reference {3} Table 1:FDA approved SGLT2 inhibitors and their outcomes Abbreviations: FDA, Food and Drug Administration: SGLT2, Sodium-Glucose Cotransporter-2; HbAlc, Hemoglobin Alc; BP, blood pressure; MI, myocardial infarction, LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol. Taken from reference [2}