New insights into cellular links between sodium–glucose cotransporter‐2 inhibitors and ketogenesis

Sodium–glucose cotransporter‐2 inhibitors (SGLT2is) are a newly developed class of highly effective antidiabetic therapies that normalize hyperglycemia via urinary glucose excretion. However, they may be accompanied by certain side effects that negatively impact their therapeutic benefits. SGLT2is i...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2022-12, Vol.123 (12), p.1879-1890
Main Authors: Yaribeygi, Habib, Maleki, Mina, Butler, Alexandra E., Jamialahmadi, Tannaz, Sahebkar, Amirhossein
Format: Article
Language:English
Subjects:
beta‐oxidation
Diabetes mellitus
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Diabetic Ketoacidosis - chemically induced
Diabetic Ketoacidosis - drug therapy
Fatty acids
free fatty acids
gluconeogenesis
Glucose
Humans
Hyperglycemia
Hypoglycemic Agents - adverse effects
Ketoacidosis
Ketogenesis
Ketone Bodies - therapeutic use
ketone body
Lipolysis
Side effects
Sodium
Sodium-glucose cotransporter
Sodium-Glucose Transporter 2 Inhibitors - adverse effects
sodium–glucose cotransporter‐2 inhibitors
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Summary:Sodium–glucose cotransporter‐2 inhibitors (SGLT2is) are a newly developed class of highly effective antidiabetic therapies that normalize hyperglycemia via urinary glucose excretion. However, they may be accompanied by certain side effects that negatively impact their therapeutic benefits. SGLT2is induce a metabolic shift from glucose to fatty acids and thus increase lipolysis which, in turn, induces ketogenesis. The complete pathways linking SGLT2is to ketoacidosis have not yet been fully elucidated, though much is now known. Therefore, in this mechanistic study, we present the current knowledge and shed light upon the possible cellular pathways involved. A deeper understanding of the possible links between SGLT2is and ketogenesis could help to prevent adverse side effects in diabetic patients treated with these drugs.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.30327