SGLT2 inhibition and glucagon secretion in humans

Diabetes & Metabolism
C SaponaroCaroline Bonner

Abstract

With the increasing prevalence of type 2 diabetes (T2D), therapies aimed at delineating diabetes pathophysiology and understanding their mechanisms of action are of critical importance. As such, growing interest in the clinical pharmacology of sodium-glucose cotransporter 2 (SGLT2) and its inhibition by gliflozins in the treatment of T2D is becoming increasingly evident. SGLT2 inhibition results in urinary glucose excretion, thereby reducing blood glucose levels. The importance of this homoeostasis mechanism is evident from several clinical trials demonstrating that patients taking this class of compounds have reductions in glycaemia, body weight and blood pressure compared with other antidiabetic agents. Yet, while such outcomes are very encouraging, some studies have reported elevated plasma glucagon levels and endogenous glucose production (EGP), two traits that are already prevalent in T2D. However, these findings were later explained by the specific expression of SGLT2 by pancreatic alpha cells, where glucagon secretion is directly regulated. Although conflicting data are now emerging on SGLT2 regulation of glucagon secretion, as SGLT2 is not expressed in the intestines, circulating glucagon concentrations are most likely ...Continue Reading

Associated Clinical Trials

May 30, 2019·Aldo Ferreira Hermosillo

Citations

Mar 6, 2019·The Journal of Clinical Endocrinology and Metabolism·Peter S HamblinLeon A Bach
Apr 18, 2020·The Journal of Clinical Endocrinology and Metabolism·Nicola FlemingElif I Ekinci
Aug 21, 2019·International Journal of Environmental Research and Public Health·Anastasios TentolourisNikolaos Tentolouris
Jun 10, 2020·JGH Open : an Open Access Journal of Gastroenterology and Hepatology·Thomas MarjotJeremy W Tomlinson
Feb 1, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jose Luis GórrizMaria Jose Soler
May 8, 2019·JACC. Basic to Translational Science·Alessandro Pocai
Feb 4, 2021·Heart Failure Reviews·Maja NikolicVladimir Jakovljevic
Oct 3, 2020·Diabetes·Sofie HædersdalTina Vilsbøll
Feb 11, 2021·Postgraduate Medical Journal·Priti MeenaAlok Mantri

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