SGLT2 inhibitors increase the risk of diabetic ketoacidosis developing in the community and during hospital admission
Open accessAbstract
CONTEXT: Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVE: To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. DESIGN: Retrospective, multicenter, controlled cohort study. SETTING: All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. PATIENTS: Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes. MAIN OUTCOME MEASURES: In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. RESULTS: There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). CONCLUSIONS: SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.
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To date, few cases have been reported of euDKA associated with SGLT2 inhibitor use and ketogenic diets in patients with T2DM.
“To date, few cases have been reported of euDKA associated with SGLT2 inhibitor use and ketogenic diets in patients with T2DM.”
From Euglycemic Diabetic Ketoacidosis Caused by SGLT2 Inhibitors and a Ketogenic Diet: A Case Series and Review of Literature (2021) · cites this paper as [19]
The Results (p. 2) report DKA in SGLT2 inhibitor users with type 2 diabetes, including cases with glucose below 250 mg/dL; the Methods (p. 2) recognize euglycemic DKA. The paper does not report how many published cases involved ketogenic diets or establish that there were few such cases. Its discussion of reduced carbohydrate intake concerns fasting, not ketogenic diets. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe risk of peri-operative DKA in patients taking an SGLT2 inhibitor is higher than in those who are not (1.02 vs. 0.69 per 1000 patients, OR 1.48, 95%CI 1.02-2.15, p=0.037).
“Data suggest that the risk of peri‐operative DKA in those patients taking an SGLT2 inhibitor is higher than in those who are not (1.02 vs. 0.69 per 1000 patients, OR 1.48, 95%CI 1.02–2.15, p = 0.037) [92].”
The Results summary (p. 2) reports the quoted rates, odds ratio, confidence interval and p-value for DKA overall in SGLT2i users versus nonusers—not for peri-operative DKA specifically. The Key finding (p. 7) says most DKA cases developing during admission occurred in the context of surgery and fasting, supporting the peri-operative concern but not those numerical estimates for that setting. (LLM, conf=0.90)
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References 25 · Cited by 126
- Authors
- Hamblin, P. S., Wong, R., Ekinci, E. I., Fourlanos, S., Shah, S., Jones, A. R., Hare, M. J. L., Calder, G. L., Epa, D. S., George, E. M., Giri, R., Kotowicz, M. A., Kyi, M., Lafontaine, N., MacIsaac, R. J., Nolan, B. J., O’Neal, D. N., Renouf, D., Varadarajan, S., Wong, J., Xu, S., & Bach, L. A.
- Affiliations
- The University of Melbourne (AU)
- Eastern Health (AU)
- The Royal Melbourne Hospital (AU)
- Monash Medical Centre (AU)
- Western Health (AU)
- The Alfred Hospital (AU)
- St Vincent's Hospital Melbourne (AU)
- Barwon Health (AU)
- Northern Health (AU)
- Werribee Mercy Hospital, Werribee, Victoria, Australia
- Peninsula Health (AU)
- Corresponding author
- Hamblin, Peter S
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-03-05
- Volume
- 104
- Issue
- 8
- Pages
- 3077-3087
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2920630596
- Semantic Scholar
- 7c9ba35e6dc821ccf378b593041cafc7078fc2be
- Cited by
- 126
- References
- 25
- Citations by year
- 2026: 7 · 2025: 21 · 2024: 16 · 2023: 17 · 2022: 13 · 2021: 19 · 2020: 26 · 2019: 7
- FWCI
- 13.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- 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 › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- diabetic ketoacidosis, SGLT2 inhibitors, type 2 diabetes, hospitalization, adverse drug reactions, hospitalized patients, drug safety, antidiabetic drugs
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Adult, Aged, Aged, 80 and over, Blood Glucose, Diabetes Mellitus, Type 2, Female, Hospitalization, Humans, Male, Middle Aged, Retrospective Studies, Diabetic Ketoacidosis
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