SGLT-2 inhibitors associated euglycemic and hyperglycemic DKA in a multicentric cohort
Open accessAbstract
Euglycemic diabetic ketoacidosis (EuDKA) secondary to Sodium-glucose co-transporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2D) is a rare but increasingly reported phenomenon. Not much is known about the burden of EuDKA in patients on SGLT2i or the associated factors. This retrospective cohort study tries to delineate the differences in factors associated with the development of EuDKA as compared to hyperglycemic DKA. We conducted a multicentre, retrospective study across three tertiary care centers under Weill Cornell affiliated-Hamad Medical Corporation, Qatar. The cohort comprised of T2D patients on SGLT2i who developed DKA between January 2015 to December 2020. The differences between the subjects who developed EuDKA or hyperglycaemic DKA (hDKA) were analyzed. A total of 9940 T2D patients were on SGLT2i during 2015–2020, out of which 43 developed DKA (0.43%). 25 developed EuKDA, whereas 18 had hDKA. The point prevalence of EuDKA in our cohort was 58.1%. EuDKA was most common in patients using canagliflozin, followed by empagliflozin and Dapagliflozin (100%, 77%, and 48.3%, respectively). Overall, infection (32.6%) was the most common trigger for DKA, followed by insulin non-compliance (13.7%). Infection was the only risk factor with a significant point estimate between the two groups, being more common in hDKA patients (p-value 0.006, RR 2.53, 95% CI 1.07–5.98). Canagliflozin had the strongest association with the development of EuDKA and was associated with the highest medical intensive care unit (MICU) admission rates (66.6%). In T2D patients on SGLT2i, infection is probably associated with an increased risk of developing EuDKA. The differential role of individual SGLT2i analogs is less clear and will need exploration by more extensive prospective studies.
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Euglycemic diabetic ketoacidosis (DKA) is a rare but potentially serious phenomenon associated with treatment with SGLT2 inhibitors, especially in those with multimorbidity who reside in post-acute and long-term care (PALTC) settings, with infection being the most common trigger.
“Euglycemic diabetic ketoacidosis (DKA) is a rare but potentially serious phenomenon associated with treatment with SGLT2 inhibitors, especially in those with multimorbidity who reside in post-acute and long-term care (PALTC) settings, with infection being the most common trigger”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [147]
The Discussion calls SGLT2 inhibitor–associated EuDKA rare, and the Conclusion reports that infection primarily triggered DKA in the cohort, including EuDKA. The Results (Precipitating factors; page unavailable) specify that infection was more common in hyperglycemic DKA than EuDKA. The study examined patients admitted to three tertiary-care hospitals, not PALTC residents; its suggestion that people with more complicated diabetes may be prone to EuDKA does not establish particular risk in PALTC residents with multimorbidity. (LLM, conf=0.88)
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- Authors
- Ata, F., Yousaf, Z., Khan, A. A., Razok, A., Akram, J., Ali, E. A. H., Abdalhadi, A., Ibrahim, D. A., Al Mohanadi, D. H. S. H., & Danjuma, M. I.
- Affiliations
- Hamad General Hospital (QA)
- Hamad Medical Corporation (QA)
- Corresponding author
- Yousaf, Zohaib
- ORCID
- Venue
- Scientific Reports
- Published
- 2021-05-13
- Volume
- 11
- Issue
- 1
- Pages
- 10293-10293
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8119406
- OpenAlex
- W3163812846
- Cited by
- 87
- References
- 55
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 18 · 2023: 18 · 2022: 15 · 2021: 3
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Qatar University QSpace (Qatar University) (submittedVersion)
- Qatar National Library (cc-by)
- Funders
- Hamad Medical Corporation
- Qatar National Library
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Keywords
- SGLT2 inhibitors, euglycemic diabetic ketoacidosis, type 2 diabetes, canagliflozin, empagliflozin, dapagliflozin, infection as risk factor, intensive care unit admission
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Blood Glucose, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Male, Middle Aged, Cohort Studies, Diabetic Ketoacidosis
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