Ketoacidosis at Hypoglycemic and Low Glucose Levels Associated with SGLT2 Inhibitor Use: A Descriptive Systematic Review of Published Cases
- 1Division of Emergency and Disaster Medicine, Tohoku Medical and Pharmaceutical University Hospital, 1-12-1 Fukumuro, Miyaginoku, Sendai 983-8512, Miyagi, Japan
Abstract
Background/Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly used for heart failure and chronic kidney disease beyond type 2 diabetes, increasing exposure among people without diabetes. Ketoacidosis is a recognized complication, but presentations at low blood glucose (<100 mg/dL) fall outside the familiar euglycemic diabetic ketoacidosis (DKA) alert and are easily missed. We aimed to describe the clinical phenotype of such cases; this review was not registered. Methods: We systematically searched PubMed and Web of Science (to 25 June 2026) and included only peer-reviewed case reports and case series describing ketoacidosis with a documented blood glucose <100 mg/dL at or near diagnosis during ongoing SGLT2 inhibitor use or within approximately two weeks after discontinuation. Reporting completeness was assessed with the CARE (Case Report) checklist; analyses were descriptive. Results: Fifteen cases met the criteria (median age 61 years; 6/15 nondiabetic; 6/15 receiving it for heart failure). Median glucose was 68 mg/dL (n = 15; 10/15 <70). Metabolic acidosis was frequently marked (median pH 7.17 [n = 14], anion gap 19.9 [n = 13], β-hydroxybutyrate 5.0 mmol/L [n = 11]). Fasting or poor oral intake was the commonest precipitant (11/15). Among six cases with extractable timing, three occurred within 24 h. Blood glucose was not correlated with β-hydroxybutyrate in this small exploratory sample (Spearman ρ = −0.20; n = 11; p = 0.56). One death occurred (aspiration). Conclusions: This descriptive synthesis characterizes ketoacidosis occurring at hypoglycemic and low glucose levels reported in SGLT2 inhibitor users, including nondiabetic and cardiorenal patients. The design cannot establish incidence, risk, or causality (very low certainty of evidence); clinicians should nonetheless consider ketoacidosis in exposed patients with anion-gap acidosis or ketosis even without hyperglycemia.
Related
- Euglycemic SGLT2 Inhibitor-Associated Ketoacidosis in a Nondiabetic Patient: A Case Report.
- Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in an adolescent with type 2 diabetes.
- Favorable CGM metrics do not exclude SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis: an educational case report with narrative review of literature
- Rapid-onset type 1 diabetes mellitus and diabetic ketoacidosis : A case series of programmed cell death 1 inhibitor-associated endocrine toxicity in China : Four case reports
- Immune Checkpoint Inhibitor‐Induced Diabetic Ketoacidosis in a Patient With Pre‐Existing Type 2 Diabetes: A Case Report
BibTeX
@article{itagaki2026ketoacidosis,
title = {{Ketoacidosis at Hypoglycemic and Low Glucose Levels Associated with SGLT2 Inhibitor Use: A Descriptive Systematic Review of Published Cases}},
author = {Hideya Itagaki and Tomoyuki Endo},
journal = {Journal of Clinical Medicine},
year = {2026},
month = sep,
doi = {10.3390/jcm15197595},
url = {https://www.mdpi.com/2077-0383/15/19/7595},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ketoacidosis at Hypoglycemic and Low Glucose Levels Associated with SGLT2 Inhibitor Use: A Descriptive Systematic Review of Published Cases
AU - Hideya Itagaki
AU - Tomoyuki Endo
PY - 2026
DA - 2026/09/30
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15197595
UR - https://www.mdpi.com/2077-0383/15/19/7595
AB - Background/Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly used for heart failure and chronic kidney disease beyond type 2 diabetes, increasing exposure among people without diabetes. Ketoacidosis is a recognized complication, but presentations at low blood glucose (<100 mg/dL) fall outside the familiar euglycemic diabetic ketoacidosis (DKA) alert and are easily missed. We aimed to describe the clinical phenotype of such cases; this review was not registered. Methods: We systematically searched PubMed and Web of Science (to 25 June 2026) and included only peer-reviewed case reports and case series describing ketoacidosis with a documented blood glucose <100 mg/dL at or near diagnosis during ongoing SGLT2 inhibitor use or within approximately two weeks after discontinuation. Reporting completeness was assessed with the CARE (Case Report) checklist; analyses were descriptive. Results: Fifteen cases met the criteria (median age 61 years; 6/15 nondiabetic; 6/15 receiving it for heart failure). Median glucose was 68 mg/dL (n = 15; 10/15 <70). Metabolic acidosis was frequently marked (median pH 7.17 [n = 14], anion gap 19.9 [n = 13], β-hydroxybutyrate 5.0 mmol/L [n = 11]). Fasting or poor oral intake was the commonest precipitant (11/15). Among six cases with extractable timing, three occurred within 24 h. Blood glucose was not correlated with β-hydroxybutyrate in this small exploratory sample (Spearman ρ = −0.20; n = 11; p = 0.56). One death occurred (aspiration). Conclusions: This descriptive synthesis characterizes ketoacidosis occurring at hypoglycemic and low glucose levels reported in SGLT2 inhibitor users, including nondiabetic and cardiorenal patients. The design cannot establish incidence, risk, or causality (very low certainty of evidence); clinicians should nonetheless consider ketoacidosis in exposed patients with anion-gap acidosis or ketosis even without hyperglycemia.
SN - 2077-0383
ER -