One Case of Euglycemic Diabetic Ketoacidosis Caused by Metformin Hydrochloride and Empagliflozin Tablets(Ⅰ)

doi:10.19803/j.1672-8629.20240845

Abstract

Abstract: Objective To explore the mechanisms of and risk factors for empagliflozin-induced euglycemic diabetic ketoacidosis (euDKA) so as to ensure the safety of medication. Methods One case of euDKA induced by metformin hydrochloride and empagliflozin tablets（Ⅰ）was retrospectively analyzed. Related literature was reviewed to find out more about the pathogenesis. Results The patient exhibited ketoacidosis with normal blood glucose levels, but his conditions were improved after discontinuation of the drug, fluid replacement, and insulin therapy. Literature suggested that euDKA was associated with insulin deficiency. Conclusion Empagliflozin may cause euDKA. The symptoms are usually insidious and prone to missed diagnosis. Clinically, high-risk patients deserve more attention. Pharmaceutical care should be enhanced to ensure the safety of patients.

Key words: Metformin Hydrochloride and Empagliflozin Tablets（Ⅰ）, Euglycemic Diabetic Ketoacidosis, SGLT2 Inhibitor, Diabetic Ketoacidosis, Adverse Drug Reaction

CLC Number:

R977
R994.11

ZHENG Guimei, XIE Zeyu, CHENG Xiaoling, LIU Jiang, ZHANG Yueyan, CAO Weiling. One Case of Euglycemic Diabetic Ketoacidosis Caused by Metformin Hydrochloride and Empagliflozin Tablets(Ⅰ)[J]. Chinese Journal of Pharmacovigilance, 2025, 22(6): 693-695.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240845

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I6/693

References

[1] SUN H, SAEEDI P, KARURANGA S, et al.IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045[J]. Diabetes Research and Clinical Practice, 2022, 183: 109119.
[2] LUKIC N, MACVANIN MT, GLUVIC Z, et al.SGLT-2 Inhibitors: The Next-Generation Treatment for Type 2 Diabetes Mellitus[J]. Current Medicinal Chemistry. 2024, 31(30): 4781-4806.
[3] American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024[J]. Diabetes Care, 2024, 47(Suppl 1): S158-S178.
[4] Chinese Diabetes Society, ZHU DL, GUO LX.Guidelines for the Prevention and Treatment of Diabetes Mellitus in China (2024 edition)[J]. Chinese Journal of Diabetes Mellitus(中华糖尿病杂志), 2025, 17(1): 1-100.
[5] QIU H, NOVIKOV A, VALLON V.Ketosis and Diabetic Ketoacidosis in Response to SGLT2 Inhibitors: Basic Mechanisms and Therapeutic Perspectives[J]. Diabetes/Metabolism Research & Reviews, 2017, 33(5): e2886.
[6] Revision Committee of Chinese Guidelines for Hypertension Prevention and Treatment, Hypertension Alliance (China), Hypertension Branch of China International Exchange, et al. Chinese Guidelines for Hypertension Prevention and Treatment (2024 Revision)[J]. Chinese Journal of Hypertension(中华高血压杂志), 2024, 32(7): 603-700.
[7] MORACE C, LORELLO G, BELLONE F, et al.Ketoacidosis and SGLT2 Inhibitors: a Narrative Review[J]. Metabolites, 2024, 14(5): 264.
[8] CHOW E, CLEMENT S, GARG R.Euglycemic Diabetic Ketoacidosis in the Era of SGLT-2 Inhibitors[J]. BMJ Open Diabetes Research & Care, 2023, 11(5): e003666.
[9] European Medicines Agency. SGLT2 Inhibitors: PRAC Makes Recommendations to Minimise Risk of Diabetic Ketoacidosis[EB/OL]. (2016-02-12)[2025-05-02]. https://www.ema.europa.eu/en/news/sglt2-inhibitors-prac-makes-recommendations-minimise-risk-diabetic-ketoacidosis.
[10] OGAWA W, SAKAGUCHI K.Euglycemic Diabetic Ketoacidosis Induced by SGLT2 Inhibitors: Possible Mechanism and Contributing Factors[J]. Journal of Diabetes Investigation, 2016, 7: 135-138.
[11] BLAU JE, TELLA SH, TAYLOR SI, et al.Ketoacidosis Associated with SGLT-2 Inhibitor Treatment: Analysis of FAERS Data[J]. Diabetes/Metabolism Research & Reviews, 2017, 33: e2924.
[12] LENG L, LIN JD, LI M.Interruption of Insulin Treatment in Type 2 Diabetes Patients with Euglycemic Diabetic Ketoacidosis Caused by Dapagliflozin: a Case Report[J]. Chinese Journal of Diabetes(中国糖尿病杂志), 2023, 15(Z2): 185-188.
[13] CAI J, WEI J, JI LW.Two Cases of Euglycemic Diabetic Ketosis Induced by Dapagliflozin Tablets[J]. Chinese Journal of Pharmaco-vigilance(中国药物警戒), 2021, 18(3): 271-273.
[14] CAI J, LIU SM, LI HXL, et al.Literature Analysis of Dapagliflozin-induced Euglycemic Diabetic Ketoacidosis[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2020, 17(11): 808-812.
[15] JIAO LT, ZOU F, WEI ML, et al.Euglycemic Diabetic Ketoacidosis Induced by Dapagliflozin: a Case Report[J]. Journal of Nanchang University (Medical Sciences)(南昌大学学报医学版), 2023, 63(5): 92-95.
[16] UMPIERREZ GE, DAVIS GM, ELSAYED NA, et al.Hyperglycemic Crises in Adults with Diabetes: a Consensus Report[J]. Diabetes Care, 2024, 47(8): 1257-1275.
[17] Goldenberg RM, Berard LD, Cheng AYY, et al.SGLT2 Inhibitor-Associated Diabetic Ketoacidosis: Clinical Review and Recomm-endations for Prevention and Diagnosis[J]. Clinical Therapeutics, 2016, 38: 2654-2664.
[18] DAVE CV, SCHNEEWEISS S, KIM D, et al.Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study[J]. Annals of Internal Medicine, 2019, 171(4): 248-256.