DOI: 10.12890/2025_005210
Mottling as an early sign of euglycemic ketoacidosis induced by SGLT-2 inhibitors
Authors
besart-memeti@hotmail.com
Keywords
Euglycemic ketoacidosis, SGLT-2 inhibitors, mottling, dapagliflozin, diabetes managementAbstract
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.
References
- Prytherch DR, Smith GB, Schmidt PE, Featherstone PI. ViEWS—Towards a national early warning score for detecting adult inpatient deterioration. Resuscitation 2010;81:932–937.
- Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium–glucose cotransporter 2 inhibition. Diabetes Care 2015;38:1687–1693.
- Blau JE, Tella SH, Taylor SI, Rother KI. Ketoacidosis associated with SGLT2 inhibitor treatment: analysis of FAERS data. Diabetes Metab Res Rev 2017;33:10.
- Rawla P, Vellipuram AR, Bandaru SS, Raj J. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. Endocrinol Diabetes Metab Case Rep 2017;2017:17-0081.
- Ahmed I, Raja UY, Wahab MU, Rehman T, Ishtiaq O, Aamir AH, et al. Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study. BMC Endocr Disord 2022;22:247.
- Garay PS, Zuniga G, Lichtenberg R. A case of euglycemic diabetic ketoacidosis triggered by a ketogenic diet in a patient with type 2 diabetes using a sodium–glucose cotransporter 2 inhibitor. Clin Diabetes 2020;38:204–207.
- Hawkins AM, Jackson RV, White H, Vardesh DL. SGLT2-Inhibitor induced euglycemic ketoacidosis in acute surgical patients. J Case Rep Images in Surg 2017;3:41–46.
- Hariri G, Joffre J, Leblanc G, Bonsey M, Lavillegrand JR, Urbina T, et al. Narrative review: clinical assessment of peripheral tissue perfusion in septic shock. Ann Intensive Care 2019;9:37.
- Ait-Oufella H, Lemoinne S, Boelle PY, Galbois A, Baudel JL, Lemant J, et al. Mottling score predicts survival in septic shock. Intensive Care Med 2011;37:801–807.
- Dumas G, Lavillegrand JR, Joffre J, Bigé N, de-Moura EB, Baudel JL, et al. Mottling score is a strong predictor of 14-day mortality in septic patients whatever vasopressor doses and other tissue perfusion parameters. Crit Care 2019;23:211.
