Anest. intenziv. Med. 2024;35(2):116-121 | DOI: 10.36290/aim.2024.019

Euglycemic ketoacidosis associated with SGLT2 inhibitors and DPP4 inhibitors - discussion of case reportsCase Report

©itina M.1-3, ©rámek V.1
1 Anesteziologicko­‑resuscitační klinika, FN u sv. Anny, Brno
2 Oddělení Biostatistiky, International Clinical Research Center, FN u sv. Anny, Brno
3 Ústav patologické fyziologie, Lékařská fakulta, Masarykova univerzita, Brno

Euglycemic ketoacidosis is a rare but potentially fatal complication of treatment with SGLT2 inhibitors (gliflozins). However, similar euglycemic ketoacidosis may rarely occur with other antidiabetic drugs or conditions such as pregnancy or alcohol abuse. We describe 3 cases of our patients with euglycemic ketoacidosis associated with gliflozins and 1 case associated with the DPP4 inhibitor sitagliptin and discuss in detail the acid-base disturbances present and the distinction of euglycemic ketoacidosis from classical ketoacidosis in type 1 diabetes.

Keywords: gliflozins, SGLT2 inhibitors, euglycemic ketoacidosis, hyperchloremic acidosis, diabetes mellitus.

Received: February 7, 2024; Revised: March 25, 2024; Accepted: April 16, 2024; Prepublished online: May 7, 2024; Published: June 24, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
©itina M, ©rámek V. Euglycemic ketoacidosis associated with SGLT2 inhibitors and DPP4 inhibitors - discussion of case reports. Anest. intenziv. Med. 2024;35(2):116-121. doi: 10.36290/aim.2024.019.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023 Oct 1;44(37):3627-3639. doi: 10.1093/eurheartj/ehad195. Erratum in: Eur Heart J. 2024 Jan 1;45(1):53. PMID: 37622666. Go to original source... Go to PubMed...
    2. Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations. Kidney Int Rep. 2022;7(11):2546-2547. doi:10.1016/j.ekir.2022. 08. 016. Go to original source...
    3. Long B, Lentz S, Koyfman A, Gottlieb M. Euglycemic diabetic ketoacidosis: Etiologies, evaluation, and management. Am J Emerg Med. 2021;44:157-160. doi:10.1016/j.ajem.2021. 02. 015. Go to original source...
    4. Li N, Chen R, Liu K. Sodium­‑Glucose Cotransporter Inhibitors for the Treatment of Type 1 Diabetes Mellitus. Clin Drug Investig. 2020;40(11):991-1000. doi:10.1007/s40261-020-00949-9. Go to original source... Go to PubMed...
    5. Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System. Diabetologia. 2017;60(8):1385-1389. doi:10.1007/s00125-017-4301-8. Go to original source... Go to PubMed...
    6. Gibb FW, Teoh WL, Graham J, Lockman KA. Risk of death following admission to a UK hospital with diabetic ketoacidosis. Diabetologia. 2016;59(10):2082-2087. doi:10.1007/s00125-016-4034-0. Go to original source... Go to PubMed...
    7. Sitina M, Lukes M, Sramek V. Empagliflozin­‑associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis. BMC Endocr Disord. 2023;23(1):81. doi:10.1186/s12902-023-01339-w. Go to original source... Go to PubMed...
    8. Palmer BF, Clegg DJ. Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy. Clin J Am Soc Nephrol CJASN. 2021;16(8):1284-1291. doi:10.2215/CJN.17621120. Go to original source... Go to PubMed...
    9. Thiruvenkatarajan V, Meyer EJ, Nanjappa N, Van Wijk RM, Jesudason D. Perioperative diabetic ketoacidosis associated with sodium­‑glucose co­‑transporter-2 inhibitors: a systematic review. Br J Anaesth. 2019;123(1):27-36. doi:10.1016/j.bja.2019. 03. 028. Go to original source...
    10. ©itina M, ©rámek V. Patogeneze euglykemické ketoacidózy asociované se SGLT2 inhibitory. Anest intenziv Med. 2024;35(2):98-103. doi:10.36290/aim.2024.019. Go to original source...
    11. Figge J, Rossing TH, Fencl V. The role of serum proteins in acid­‑base equilibria. J Lab Clin Med. 1991;117(6):453-467.
    12. Figge J, Mydosh T, Fencl V. Serum proteins and acid­‑base equilibria: a follow­‑up. J Lab Clin Med. 1992;120(5):713-719.
    13. Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of Metabolic Acid-Base Disturbances in Critically Ill Patients. Am J Respir Crit Care Med. 2000;162(6):2246-2251. doi:10.1164/ajrccm.162. 6. 9904099. Go to original source...
    14. Kellum JA. Clinical review: reunification of acid­‑base physiology. Crit Care Lond Engl. 2005;9(5):500-507. doi:10.1186/cc3789. Go to original source... Go to PubMed...
    15. Helmersson-Karlqvist J, Höög Hammarström K, Palmberg K, Backman-Johansson C. Evaluation of Nova StatStrip and FreeStyle Precision Pro blood ketone tests using 3-hydroxybutyrate doped samples. J Clin Lab Anal. 2019;33(4):e22851. doi:10.1002/jcla.22851. Go to original source... Go to PubMed...
    16. Oh MS, Banerji MA, Carroll HJ. The mechanism of hyperchloremic acidosis during the recovery phase of diabetic ketoacidosis. Diabetes. 1981;30(4):310-313. doi:10.2337/diab.30. 4. 310. Go to original source...
    17. Charoenpiriya A, Chailurkit L, Ongphiphadhanakul B. Comparisons of biochemical parameters and diabetic ketoacidosis severity in adult patients with type 1 and type 2 diabetes. BMC Endocr Disord. 2022;22(1):7. doi:10.1186/s12902-021-00922-3. Go to original source... Go to PubMed...
    18. Warming­‑Larsen A. Renal excretion of ketone bodies. II. Acta Med Scand. 1952;144(3):197-200. doi:10.1111/j.0954-6820.1952.tb15684.x Go to original source... Go to PubMed...
    19. Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. 14th edition. Elsevier; 2021.
    20. Adrogué HJ, Wilson H, Boyd AE, Suki WN, Eknoyan G. Plasma acid­‑base patterns in diabetic ketoacidosis. N Engl J Med. 1982;307(26):1603-1610. doi:10.1056/NEJM198212233072603. Go to original source... Go to PubMed...
    21. Schwetz V, Eisner F, Schilcher G, Eller K, Plank J, Lind A, et al. Combined metformin­‑associated lactic acidosis and euglycemic ketoacidosis. Wien Klin Wochenschr. 2017 Sep;129(17-18):646-649. doi: 10.1007/s00508-017-1251-6. Epub 2017 Sep 1. PMID: 28865058; PMCID: PMC5599436. Go to original source... Go to PubMed...
    22. Bonsignore A, Pozzi F, Fraternali Orcioni G, Ventura F, Palmiere C. Fatal metformin overdose: case report and postmortem biochemistry contribution. Int J Legal Med. 2014;128(3):483-492. doi:10.1007/s00414-013-0927-3. Go to original source... Go to PubMed...
    23. Qi H, Nielsen PM, Schroeder M, Bertelsen LB, Palm F, Laustsen C. Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats. Diabetologia. 2018;61(2):445-454. doi:10.1007/s00125-017-4445-6. Go to original source... Go to PubMed...
    24. Kubera B, Hubold C, Wischnath H, Zug S, Peters A. Rise of ketone bodies with psychosocial stress in normal weight men. Psychoneuroendocrinology. 2014;45:43-48. doi:10.1016/j.psyneuen.2014. 03. 008. Go to original source...
    25. Christopher MM, Broussard JD, Fallin CW, Drost NJ, Peterson ME. Increased serum d­‑lactate associated with diabetic ketoacidosis. Metabolism. 1995;44(3):287-290. doi:10.1016/0026-0495(95)90156-6. Go to original source... Go to PubMed...
    26. Bo J, Li W, Chen Z, Wadden DG, Randell E, Zhou H, et al. D­‑lactate: a novel contributor to metabolic acidosis and high anion gap in diabetic ketoacidosis. Clin Chem. 2013 Sep;59(9):1406-7. doi: 10.1373/clinchem.2013.208777. Epub 2013 Jul 8. PMID: 23836843. Go to original source... Go to PubMed...
    27. Lu J, Zello GA, Randell E, Adeli K, Krahn J, Meng QH. Closing the anion gap: Contribution of d­‑lactate to diabetic ketoacidosis. Clin Chim Acta. 2011;412(3-4):286-291. doi:10.1016/j.cca 2010. 10. 020. Go to original source...
    28. Stewart GW. Pyroglutamate acidosis 2023. A review of 100 cases. Clin Med Lond Engl. 2024;24(2):100030. doi:10.1016/j.clinme.2024.100030. Go to original source... Go to PubMed...
    29. Douros A, Lix LM, Fralick M, Dell'Aniello S, Shah BR, Ronksley PE, et al; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Sodium­‑Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Ann Intern Med. 2020 Sep 15;173(6):417-425. doi: 10.7326/M20-0289. Epub 2020 Jul 28. PMID: 32716707. Go to original source... Go to PubMed...
    30. Omar B, Ahrén B. Pleiotropic Mechanisms for the Glucose­‑Lowering Action of DPP-4 Inhibitors. Diabetes. 2014;63(7):2196-2202. doi:10.2337/db14-0052. Go to original source... Go to PubMed...

    Return to the content


    Anesteziologie a intenzivní medicína

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.