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Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors

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Diabetes: from Research to Clinical Practice

Part of the book series: Advances in Experimental Medicine and Biology ((AIM,volume 1307))

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 inhibitors, current status of SGLT2 inhibitors in the management of type 2 diabetes and their beneficial effects in addition to glycemic control.

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Abbreviations

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

CANVAS:

Canagliflozin Cardiovascular Assessment Study

CK:

cytokeratin

CKD:

chronic kidney disease

CV:

cardiovascular

CVD:

cardiovascular disease

CVD-REAL:

Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors

CVOT:

cardiovascular outcome trial

DECLARE TIMI 58:

Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58

DKA:

diabetic ketoacidosis

eGFR:

estimated glomerular filtration rate

E-LIFT:

Effect of Empagliflozin on Liver Fat

EMA:

European Medicines Agency

EMPA-REG OUTCOME:

Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose

FGF 21:

fibroblast growth factor 21

FRG:

familial renal glucosuria

GGT:

gamma glutamyl transpeptidase

GLP-1r:

glucagon like peptide-1 receptor

GLUT:

glucose transporter

HbA1C:

glycated hemoglobin

HGO:

hepatic glucose output

MACE:

major adverse cardiovascular events

MRI:

magnetic resonance imaging

NAFLD:

nonalcoholic fatty liver disease

NASH:

nonalcoholic steatohepatitis

NHE:

sodium hydrogen exchanger

PCT:

proximal convoluted tubule

PDFF:

proton density fat fraction

SGLT2:

sodium-glucose cotransporter 2

UGE:

urinary glucose excretion

US FDA:

The United States Food and Drug Administration

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Acknowledgements

The authors would like to acknowledge Ganesh Jevalikar (Medanta The Medicity Hospital) for his valuable inputs for the manuscript.

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No funding was received from any source.

Conflict of Interest

Mohammad Shafi Kuchay, Khalid Jamal Farooqui, Sunil Kumar Mishra and Ambrish Mithal declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Division of Endocrinology and Diabetes, Medanta The Medicity Hospital, Gurugram, Haryana, India

    Mohammad Shafi Kuchay, Khalid Jamal Farooqui, Sunil Kumar Mishra & Ambrish Mithal

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  1. Mohammad Shafi Kuchay
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  2. Khalid Jamal Farooqui
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  3. Sunil Kumar Mishra
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Correspondence to Mohammad Shafi Kuchay .

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  1. Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden, Department of Emergency Care and Internal Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden

    Md. Shahidul Islam

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Kuchay, M.S., Farooqui, K.J., Mishra, S.K., Mithal, A. (2020). Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors. In: Islam, M.S. (eds) Diabetes: from Research to Clinical Practice. Advances in Experimental Medicine and Biology(), vol 1307. Springer, Cham. https://doi.org/10.1007/5584_2020_479

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