B. Memeti, F. Brombacher, L. Perger and S. Russmann (2025). Mottling as an Early Sign of Euglycemic Ketoacidosis Induced by SGLT-2 Inhibitors. European journal of case reports in internal medicine, 12(4), 005210. https://doi.org/10.12890/2025_005210

PubMed 40270662

[Abstract]
UNLABELLED: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have shown benefits in managing heart failure, renal insufficiency and type 2 diabetes, but euglycemic ketoacidosis, while rare, has been reported in several patients on those medications. Therefore, their potential for inducing ketoacidosis, even in the presence of normal glucose levels, requires careful monitoring. We describe the case of a 78-year-old woman with type 2 diabetes treated with the SGLT-2 inhibitor dapagliflozin and the biguanide metformin, who presented after several days of reduced food and fluid intake due to nausea and diarrhoea to the emergency department. A few hours after admission to the medical ward with a working diagnosis of infectious gastroenteritis her condition deteriorated, and mottling served as an early sign of life-threatening euglycemic ketoacidosis. The mottling score increased in parallel with the National Early Warning Score (NEWS). She was treated with intravenous fluids, continuous insulin therapy and supportive measures, resulting in rapid clinical improvement. This report highlights the importance of early recognition to prevent serious complications and underscores that mottling might be a valuable early sign in addition to classical tools such as the NEWS. Although rare, euglycemic ketoacidosis can be precipitated by factors such as starvation, dehydration or infections in patients taking SGLT-2 inhibitors. The risk might be higher in individuals on SGLT-2 inhibitors and metformin. Timely intervention and metabolic correction are essential for improving outcomes in these patients, particularly when they present with atypical symptoms.

LEARNING POINTS: Mottling can serve as an early clinical indicator of euglycemic ketoacidosis (EKA) in patients treated with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, even in the absence of circulatory shock, highlighting the importance of timely detection and intervention.Factors such as starvation, dehydration or infections can precipitate EKA in patients using SGLT-2 inhibitors, emphasising the need for careful monitoring in at-risk populations.Discontinuation of SGLT-2 inhibitors, rapid metabolic correction using fluids and insulin and avoidance of unnecessary antibiotics are essential for effective management and recovery from EKA.