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SGLT2 Inhibitors Between Benefits and Euglycemic Ketoacidosis: A Concise Review.
Luminita-Georgeta Confederat1,2, Alin-Constantin Pînzariu1,2, Ionela Lacramioara Serban1
1Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania.
International Journal of Molecular Sciences
|June 26, 2026
Summary
Sodium-glucose co-transporter 2 (SGLT2) inhibitors offer significant cardio-renal benefits for diabetes management. While concerns about euglycemic diabetic ketoacidosis (EDKA) exist, understanding risk factors allows for safe use.
Area of Science:
- Endocrinology and Metabolism
- Pharmacology
- Nephrology
Background:
- Diabetes mellitus management has evolved beyond glycemic control to include risk factor management with novel antihyperglycemic agents.
- Sodium-glucose co-transporter 2 (SGLT2) inhibitors possess pleiotropic effects, offering significant cardiovascular and renal benefits.
- Despite benefits, SGLT2 inhibitor use is sometimes limited by concerns over potential side effects, notably euglycemic diabetic ketoacidosis (EDKA).
Purpose of the Study:
- To review the multifaceted benefits of SGLT2 inhibitors.
- To critically assess the risk of EDKA associated with SGLT2 inhibitors.
- To provide guidance on balancing benefits and risks for safe SGLT2 inhibitor utilization.
Main Methods:
- Comprehensive literature search across PubMed, Web of Science, and Scopus.
- Inclusion of randomized controlled trials, retrospective studies, systematic reviews, and meta-analyses published between 2014 and 2024.
- Focused evaluation on studies detailing SGLT2 inhibitor benefits and EDKA risk factors and mechanisms.
Main Results:
- SGLT2 inhibitors are recommended as first-line therapy for patients with cardiovascular disease, heart failure, and chronic kidney disease.
- Data on the prevalence and clinical relevance of SGLT2 inhibitor side effects remain contradictory.
- Euglycemic diabetic ketoacidosis (EDKA) is a serious adverse event linked to SGLT2 inhibitors, potentially caused by mechanisms involving insulin reduction and increased glucagon.
Conclusions:
- SGLT2 inhibitors demonstrate substantial cardio-renal protective effects, establishing them as crucial in managing complex diabetes cases.
- Awareness of EDKA risk factors (e.g., carbohydrate restriction, illness, alcohol) and symptoms is vital for prompt management.
- With careful patient selection and monitoring, SGLT2 inhibitors can be used safely, maximizing their therapeutic advantages while mitigating risks.
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