The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Euglycemic Ketoacidosis in Two Patients Without Diabetes After Introduction of Sodium–Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction
Open accessAbstract
OBJECTIVE: Ketoacidosis induced by sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment has been consistently observed in clinical practice in patients with type 2 diabetes despite minimal indication from the landmark cardiovascular outcome trials. It has been postulated that individuals without diabetes will not develop this complication due to an adequate insulin secretory capacity, which will protect against significant ketone formation. Cardiovascular outcome trials examining SGLT2i use in individuals with heart failure but not diabetes have not reported ketoacidosis. RESEARCH DESIGN AND METHODS: We describe the first two case reports of severe nondiabetic ketoacidosis after initiation of an SGLT2i for the treatment of heart failure with reduced ejection fraction, and we describe the management strategies employed and implication for the pathophysiology of SGLT2i-associated ketoacidosis. RESULTS: Each individual presented with ketoacidosis triggered by reduced oral nutrition intake. For both individuals, ketoacidosis resolved with intravenous glucose administration, encouragement of consumption of oral glucose-containing fluid, and minimal insulin administration. CONCLUSIONS: These two cases demonstrate that SGLT2i-associated ketoacidosis is possible in individuals without diabetes.
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“Until recently, it was thought that people without diabetes mellitus had sufficient insulin concentrations to prevent significant ketosis, but two recent publications have challenged this [98, 99].”
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
Wiviott, S. D., Raz, I., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Silverman, M. G., Zelniker, T. A., Kuder, J. F., Murphy, S. A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812389 · Cited by 6,382
Cardiovascular and renal outcomes with empagliflozin in heart failure
Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., Januzzi, J., Verma, S., Tsutsui, H., Brueckmann, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022190 · Cited by 5,206
Empagliflozin in heart failure with a preserved ejection fraction
Anker, S. D., Butler, J., Filippatos, G., Ferreira, J. P., Bocchi, E., Böhm, M., Brunner–La Rocca, H.-P., Choi, D.-J., Chopra, V., Chuquiure-Valenzuela, E., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107038 · Cited by 4,874
Davies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetes Care · doi:10.2337/dci18-0033 · Cited by 3,518
Rossing, P., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2022) · Kidney International · doi:10.1016/j.kint.2022.06.013 · Cited by 274
Research works printed but not linked: 10
- Fralick, 2017, Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor, N Engl J Med, 376, 2300, 10.1056/NEJMc1701990 · DOI · Paper page
- Meyer, 2018, SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis: a South Australian clinical case series and Australian spontaneous adverse event notifications, Diabetes Care, 41, e47, 10.2337/dc17-1721 · DOI
- Hamblin, 2019, SGLT2 inhibitors increase the risk of diabetic ketoacidosis developing in the community and during hospital admission, J Clin Endocrinol Metab, 104, 3077, 10.1210/jc.2019-00139 · DOI · Paper page
- Peters, 2015, Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition, Diabetes Care, 38, 1687, 10.2337/dc15-0843 · DOI · Paper page
- Heidenreich, 2022, 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines, J Am Coll Cardiol, 79, 1757, 10.1016/j.jacc.2021.12.011 · DOI · Paper page
- ADS-ANZCA, 2022, Perioperative Diabetes and Hyperglycaemia Guidelines (Adults) [Position statement], ADS-ANZCA-Perioperative-Diabetes-and-Hyperglycaemia-Guidelines-Adults-November-2022-v2-Final.pdf
- Seki, 2022, Postoperative ketoacidosis with hypoglycemia in a nondiabetic patient taking dapagliflozin for heart failure: a case report, A A Pract, 16, e01570, 10.1213/XAA.0000000000001570 · DOI
- Hattersley, 2015, Type 2 diabetes, SGLT2 inhibitors, and glucose secretion, N Engl J Med, 373, 974, 10.1056/NEJMcibr1506573 · DOI
- Cohen, 1956, Renal tubular reabsorption of acetoacetate, inorganic sulfate and inorganic phosphate in the dog as affected by glucose and phlorizin, Am J Physiol, 184, 91, 10.1152/ajplegacy.1955.184.1.91 · DOI
- Thiruvenkatarajan, 2022, Sodium-glucose cotransporter 2 inhibitor-linked pericolonoscopy hyperketonemia: a retrospective study, Diabetes Care, 45, e91, 10.2337/dc21-1870 · DOI
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El‐Boghdadly, K., Dhesi, J., Fabb, P., Levy, N., Lobo, D. N., McKechnie, A., Mustafa, O., Newland‐Jones, P., Patel, A., Pournaras, D. J., et al. (2025) · Anaesthesia · doi:10.1111/anae.16541 · Cited by 147
Metadata
- Authors
- Umapathysivam, M. M., Gunton, J., Stranks, S. N., & Jesudason, D.
- Affiliations
- Flinders Medical Centre (AU)
- Flinders University (AU)
- Basil Hetzel Institute (AU)
- Corresponding author
- Umapathysivam, Mahesh M.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-11-21
- Volume
- 47
- Issue
- 1
- Pages
- 140-143
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10733652
- OpenAlex
- W4388869249
- Cited by
- 57
- References
- 6
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 19 · 2023: 1
- FWCI
- 11.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- heart failure with reduced ejection fraction, SGLT2 inhibitors, insulin secretion, insulin therapy
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Glucose, Heart Failure, Humans, Hypoglycemic Agents, Insulin, Ketosis, Sodium, Stroke Volume, Diabetic Ketoacidosis
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