Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors
In type 2 diabetes, the maladaptive upregulation of sodium-glucose cotransporter 2 (SGLT2) protein expression and activity contribute to the maintenance of hyperglycemia. By inhibiting these proteins, SGLT2 inhibitors increase urinary glucose excretion (U
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Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors Mohammad Shafi Kuchay, Khalid Jamal Farooqui, Sunil Kumar Mishra, and Ambrish Mithal Abstract
In type 2 diabetes, the maladaptive upregulation of sodium-glucose cotransporter 2 (SGLT2) protein expression and activity contribute to the maintenance of hyperglycemia. By inhibiting these proteins, SGLT2 inhibitors increase urinary glucose excretion (UGE) that leads to fall in plasma glucose concentrations and improvement in all glycemic parameters. Clinical studies have demonstrated that in patients with type 2 diabetes, SGLT2 inhibitors resulted in sustained reductions in glycated hemoglobin (HbA1C), body weight, blood pressure and serum uric acid levels. Interestingly, the cardiovascular (CV) and renal outcome trials revealed the beneficial effects of SGLT2 inhibitors on CV and renal functions. Because the benefits were seen soon after initiation of SGLT2 inhibitors, these observations are explained by effects beyond their glucose lowering capacity. SGLT2 inhibitors also reduce liver fat in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. This chapter describes the basic information about SGLT2 M. S. Kuchay (*), K. J. Farooqui, S. K. Mishra, and A. Mithal Division of Endocrinology and Diabetes, Medanta The Medicity Hospital, Gurugram, Haryana, India e-mail: drshafi[email protected]
inhibitors, current status of SGLT2 inhibitors in the management of type 2 diabetes and their beneficial effects in addition to glycemic control. Keywords
Canagliflozin · Cardiovascular health · Dapagliflozin · Empagliflozin · Ertugliflozin · Gliflozins · Ipragliflozin · Luseogliflozin · Nonalcoholic fatty liver disease · Remogliflozin · Sodium-glucose cotransporter 2 inhibitors · Tofogliflozin · Type 2 diabetes
Abbreviations ALT AST CANVAS CK CKD CV CVD CVD-REAL
CVOT
alanine aminotransferase aspartate aminotransferase Canagliflozin Cardiovascular Assessment Study cytokeratin chronic kidney disease cardiovascular cardiovascular disease Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT2 Inhibitors cardiovascular outcome trial
M. S. Kuchay et al.
DECLARE TIMI 58
DKA eGFR E-LIFT EMA EMPA-REG OUTCOME
FGF 21 FRG GGT GLP-1r GLUT HbA1C HGO MACE MRI NAFLD NASH NHE PCT PDFF SGLT2 UGE US FDA
Dapagliflozin Effect on Cardiovascular EventsThrombolysis in Myocardial Infarction 58 diabetic ketoacidosis estimated glomerular filtration rate Effect of Empagliflozin on Liver Fat European Medicines Agency Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus PatientsRemoving Excess Glucose fibroblast growth factor 21 familial renal glucosuria gamma glutamyl transpeptidase glucagon like peptide-1 receptor glucose transporter glycated hemoglobin hepatic glucose output major adverse cardiovascular events magnetic resonance imaging nonalcoholic fatty liver disease nonalcoholic steato
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