A Case of Diabetic Ketoacidosis in a Patient on an SGLT2 Inhibitor and a Ketogenic Diet: A Critical Trio Not to Be Missed

Abstract

Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DKA in a patient on an SGLT2 inhibitor and ketogenic diet (KD). A 47-year-old male with a history of poorly controlled T2DM on metformin and empagliflozin presented to the emergency department (ED) with several days of pharyngitis, dyspnea, emesis, abdominal pain, and anorexia. Of note, one month prior to this event, he presented to the ED with malaise and was found to have an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, 3+ ketonuria, and a glucose level of 7 mmol/L (127 mg/dl). Additional workup was negative, and findings were attributed to his KD. His use of empagliflozin was not identified on his medication list. At second presentation, the patient was tachypneic and tachycardic and had mild abdominal tenderness. Labs revealed anion gap 28, bicarbonate 5 mmol/l, pH 6.94, 3+ ketonuria, glucose 14.9 mmol/L (269 mg/dl), and beta-hydroxybutyrate 8.9 mmol/L. The patient was diagnosed with DKA and was treated accordingly. With closure of anion gap, the patient was transitioned to insulin and metformin, and his empagliflozin was discontinued indefinitely. Before prescribing this medication class, physicians should inquire about low-carbohydrate diets given the higher risk for DKA, though knowledge of this risk is still not widespread.

Postoperative Euglycemic Ketoacidosis in Type 2 Diabetes Associated with Sodium-Glucose Cotransporter 2 Inhibitor: Insights Into Pathogenesis and Management Strategy

“…Most patients developing euglycemic DKA may have a precipitating event. The commonly reported factors include surgery, infections including COVID-19, pericarditis, concurrent ketogenic/low carbohydrate diets, a recent change of diabetic regimen with reduction or omission of insulin dosages, nausea and vomiting, gastroparesis, pregnancy, and acute pancreatitis [12][13][14][15][16][17][18][19]. Diagnosis is often delayed or missed in these settings, like in our case presentation.…”

“…Typically, from most of the reported cases, eu-DKA has been managed similar to hyperglycemic DKA with intravenous insulin, fluids, and frequent monitoring of serum electrolytes until anion gap acidosis resolution [12][13][14][15][16][17][18][19]. But, patients could be conservatively managed like in our case.…”

“…Diagnosis is often delayed or missed in these settings, like in our case presentation. The reported blood glucose in these cases ranged from 127-212 mg/dL [12][13][14][15][16][17][18][19].…”

Euglycemic Diabetic Ketoacidosis after Discontinuing SGLT2 Inhibitor

“…No case report was found of a patient who developed EDKA following the start of keto diet for three days duration and stopped all of their oral medication for 2 days. Multiple case reports discussed the development of EDKA in patients who are on a SGLT2 inhibitor after introducing a ketogenic diet for at least one week [ 13 – 16 ]. In our case, the patient's normal level of lactic acid rules out lactic acidosis as a side effect of metformin use as a cause of DKA.…”

Sodium-Glucose Co-transporter 2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis After Bariatric Surgery: A Case and Literature Review

“…Meyer et al exposed identifiable precipitants in a series of SGLT2i-associated DKA cases, which indicated risk mitigation potential [31]. In the literature review, there are few similar DKA cases available regarding patients taking SGLT2i against the backdrop of a low carbohydrate diet [32][33][34][35]. Shaikh et al and Tauseef et al both share EDKA examples of diabetics on SGLT2i and ketogenic diets between one to three weeks [32,34].…”