Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency characterized by insulin deficiency, ketonemia, and high–anion gap metabolic acidosis. Although traditionally associated with type 1 diabetes, DKA is increasingly recognized in Type 2 Diabetes Mellitus, particularly in the context of evolving therapies and metabolic stress.
A notable shift in recent years is the emergence of euglycemic diabetic ketoacidosis (euDKA), defined as DKA with blood glucose levels <250 mg/dL. This atypical presentation frequently delays diagnosis and contributes to under recognition.
The widespread use of SGLT2 inhibitors—including empagliflozin, dapagliflozin, and canagliflozin—has transformed diabetes management by improving glycemic control and providing cardiovascular and renal benefits. However, these agents are associated with an increased risk of DKA, often presenting in a euglycemic form. Although the absolute incidence remains low (~0.1–0.3%), studies suggest a 2-7-fold increased risk in certain populations.
The pathophysiology is multifactorial, involving reduced insulin levels, increased glucagon activity, enhanced lipolysis, and accelerated ketogenesis, combined with glycosuria-induced normoglycemia. Precipitating factors such as acute illness, surgery, fasting, dehydration, and insulin dose reduction further increase susceptibility.
Clinically, euDKA presents with nonspecific symptoms such as nausea, vomiting, abdominal pain, and dyspnea, often mimicking other acute conditions. The absence of marked hyperglycemia contributes to diagnostic delay unless ketones and acid–base status are promptly assessed.
This review synthesizes current evidence on epidemiology, pathophysiology, risk factors, diagnostic challenges, and prevention strategies of SGLT2 inhibitor–associated euDKA. Early recognition, structured prevention strategies, and appropriate patient selection are essential to optimize outcomes while preserving the therapeutic benefits of this drug class.