Ketoacidosis associated with SGLT2 inhibitor treatment: analysis of FAERS data
Open accessAbstract
Background: Regulatory agencies have concluded that sodium glucose cotransporter 2 (SGLT2) inhibitors lead to ketoacidosis, but published literature on this point remains controversial. Methods: We searched the FDA Adverse Event Reporting System (FAERS) for reports of acidosis in patients treated with canagliflozin, dapagliflozin, or empagliflozin (from the date of each drug's FDA approval until May 15, 2015). We compared the number of SGLT2 inhibitor‐related reports to reports of acidosis in patients treated with the 2 most commonly used DPP4 inhibitors: sitagliptin and saxagliptin. We estimated relative risks of acidosis by relating the number of reports to cumulative drug sales (a surrogate for patient exposure). Results: FAERS contained 259 reports of acidosis (including 192 reports of ketoacidosis) for SGLT2 inhibitors compared with 477 reports of acidosis for DPP4 inhibitors (including 71 reports of ketoacidosis). Based on estimated patient exposure, the overall risk of developing acidosis was ~14‐fold higher for SGLT2 inhibitors. Among 51 SGLT2 inhibitor‐related reports with quantifiable metabolic information, 20 cases occurred in patients with type 1 diabetes (T1D), 25 in type 2 diabetes (T2D), and 6 in patients with unspecified type of diabetes. After excluding patients with T1D and focusing on patients identified as having T2D, we estimate that SGLT2 inhibitors were associated with ~7‐fold increase in developing acidosis. Seventy‐one percent had euglycemic ketoacidosis. Conclusions: Our results support the FDA's warning that SGLT2 inhibitors lead to ketoacidosis, as evidenced by an increased reporting rate for acidosis above that in a comparator population treated with DPP4 inhibitors.
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A review of SGLT2 inhibitor-associated ketoacidosis revealed that 71% of the cases were euDKA.
“A review of SGLT2 inhibitor-associated ketoacidosis revealed that 71% of the cases were euDKA. 2”
From Euglycemic Diabetic Ketoacidosis Caused by SGLT2 Inhibitors and a Ketogenic Diet: A Case Series and Review of Literature (2021) · cites this paper as [2]
In one study, 71% of people treated with SGLT2 inhibitors who developed DKA presented with glucose levels ≤250 mg/dL.
“Up to a third of people treated with SGLT2 inhibitors who developed DKA present with glucose levels <200 mg/dL (11.1 mmol/L) (239), and in one study 71% presented with glucose levels #250 mg/dL (13.9 mmol/L) (240)”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [240]
Very-low-carbohydrate eating plans should be used with caution in those taking SGLT2 inhibitors because of the potential risk of ketoacidosis.
“In addition, verylow-carbohydrate eating plans are not currently recommended for individuals who are pregnant or lactating, children, people who have renal disease, or people with or at risk for disordered eating, and these plans should be used with caution in those taking sodium-glucose cotransporter 2 inhibitors because of the potential risk of ketoacidosis (169,170).”
From 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes:<i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [170]
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- Authors
- Blau, J. E., Tella, S. H., Taylor, S. I., & Rother, K. I.
- Affiliations
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Blau, Jenny E.
- Venue
- Diabetes/Metabolism Research and Reviews
- Publisher
- Wiley
- Published
- 2017-09-29
- Volume
- 33
- Issue
- 8
- ISSN
- 1520-7552 (ISSN-L)
- 1520-7560
- PMC
- PMC5950709
- OpenAlex
- W2738105394
- Semantic Scholar
- cb9871a78fb983383e6b9af0aae1697f1a23bde2
- Cited by
- 271
- References
- 25
- Citations by year
- 2026: 26 · 2025: 29 · 2024: 51 · 2023: 32 · 2022: 37 · 2021: 29 · 2020: 26 · 2019: 21 · 2018: 18 · 2017: 2
- FWCI
- 14.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Diabetes/Metabolism Research and Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- Foundation for Anesthesia Education and Research
- National Institutes of Health (Z99 DK999999)
- National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK047049)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- SGLT2 inhibitors, ketoacidosis, euglycemic diabetic ketoacidosis, adverse drug reactions, canagliflozin, dapagliflozin, empagliflozin, DPP-4 inhibitors, sitagliptin, saxagliptin, type 2 diabetes, type 1 diabetes, drug safety, FDA Adverse Event Reporting System
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Humans, Hypoglycemic Agents, Ketosis, Databases, Factual
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