Journal ArticleDOI
Renal, metabolic and cardiovascular considerations of SGLT2 inhibition
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TLDR
The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, however, with new studies demonstrating that inhibition of renal glucose reabsorption reduces blood pressure, ameliorates glucotoxicity and induces haemodynamic effects that lead to improved cardiovascular and renal outcomes in patients with type 2 diabetes mellitus.Abstract:
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, however, with new studies demonstrating that inhibition of renal glucose reabsorption reduces blood pressure, ameliorates glucotoxicity and induces haemodynamic effects that lead to improved cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. In this Review we examine the role of SGLT2 and SGLT1 in the regulation of renal glucose reabsorption in health and disease and the effect of SGLT2 inhibition on renal function, glucose homeostasis, and cardiovascular disease.read more
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Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies.
TL;DR: This Review highlights novel concepts related to diagnosis, risk prediction, and treatment of non-alcoholic fatty liver disease that could contribute to the development of a multidisciplinary approach for endocrinologists and hepatologists working together in the management of NAFLD.
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Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial.
Ofri Mosenzon,Stephen D. Wiviott,Avivit Cahn,Aliza Rozenberg,Ilan Yanuv,Erica L. Goodrich,Sabina A. Murphy,Hiddo J.L. Heerspink,Thomas A Zelniker,Jamie P. Dwyer,Deepak L. Bhatt,Lawrence A. Leiter,Darren K. McGuire,John P.H. Wilding,Eri Toda Kato,Ingrid Gause-Nilsson,Martin Fredriksson,Peter A. Johansson,Anna Maria Langkilde,Marc S. Sabatine,Itamar Raz +20 more
TL;DR: Both the cardiorenal and renal-specific composite outcomes were improved with dapagliflozin versus placebo across various prespecified subgroups, including those defined by baseline eGFR.
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Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study.
Jan W. Eriksson,Per Lundkvist,Per-Anders Jansson,Lars Johansson,Mats Kvarnström,Linda Moris,Tasso Miliotis,Gun-Britt Forsberg,Ulf Risérus,Lars Lind,Jan Oscarsson +10 more
TL;DR: Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content and monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.
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GLP-1 and the kidney : from physiology to pharmacology and outcomes in diabetes
Marcel H. A. Muskiet,Lennart Tonneijck,Mark M. Smits,Michaël J.B. van Baar,Mark H. H. Kramer,Ewout J. Hoorn,Jaap A. Joles,Daniël H. van Raalte +7 more
TL;DR: The role of GLp-1 and the actions of associated therapies on glucose metabolism, the gut–renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM are reviewed.
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Innate immunity in diabetic kidney disease.
Sydney C.W. Tang,Wai Han Yiu +1 more
TL;DR: The authors discuss the mechanisms by which innate immune pathways might contribute to DKD as well as the therapeutic potential of targeting these pathways.
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TL;DR: In this article, the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.
Journal Article
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.
R C Turner,C Fox,Matthews,H McElroy,Carole A. Cull,Rury R. Holman,P. A. Neil,D R Hadden,D Wright,E Manley,Irene M Stratton,UK Prospective Diabetes,E M Kohner,Frighi,Michael Gnant +14 more
TL;DR: The effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.
Journal ArticleDOI
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Bernard Zinman,Christoph Wanner,John M. Lachin,David Fitchett,Erich Bluhmki,Stefan Hantel,Michaela Mattheus,Theresa Devins,Odd Erik Johansen,Hans-Juergen Woerle,Uli C. Broedl,Silvio E. Inzucchi +11 more
TL;DR: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.
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