title: New treatments for type 2 diabetes: cardiovascular protection beyond glucose lowering?
abstract: The health burden of type 2 diabetes mellitus (T2DM) is increasing worldwide, with a substantial portion of this burden being due to the development of cardiovascular (CV) disease. Multiple individual randomised clinical trials of intensive versus conventional glucose control, based on the use of traditional oral hypoglycaemic agents, have failed to convincingly show that intensive glucose control significantly reduces CV disease outcomes. In recent times, two new approaches to lowering glucose levels have become available. One targets the "incretin effect" which involves the modulation of peptide hormones that normally regulate glucose levels when nutrients are given orally. The other approach is based on inhibiting the sodium-glucose co-transporter 2 (SGLT-2) in the tubules of the kidney to promote glycosuria. Incretin-based therapies, especially glucagon-like peptide-1 receptor analogues, reduce glucose levels, with a low risk of hypoglycaemia, by increasing insulin secretion, inhibiting glucagon release and increasing satiety. Clinical and experimental studies have also shown favourable effects on CV disease risk factors such as dyslipidaemia, blood pressure, and improvements in endothelial function and cardiac contractility. Similarly, SGLT-2 inhibitors reduce glucose levels with a low risk for hypoglycaemia and have positive effects on multiple CV disease risk factors. Whether the beneficial effects of these new glucose lowering approaches on surrogate markers of CV disease risk translates to an improvement in CV events remains unknown. Several CV outcome trials are currently being performed to show that at a minimum, these novel glucose lowering agents are safe, but also have positive CV benefits.
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Australia.
authors.forename: Dilshani
authors.initials: D
authors.lastname: Jayawardene
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Australia.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Ward
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Australia.
authors.forename: David N
authors.initials: DN
authors.lastname: O'Neal
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Australia.
authors.forename: Geetha
authors.initials: G
authors.lastname: Theverkalam
authors.affiliation: Department of Cardiology, St Vincent's Hospital Melbourne & University of Melbourne, Australia.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: MacIsaac
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Australia. Electronic address: r.macisaac@unimelb.edu.au.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: MacIsaac
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D007684:Kidney Tubules / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001786:Blood Glucose; D054795:Incretins; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D052216:Glucagon-Like Peptide 1
keywords: Cardiovascular; DPP-4; GLP-1; Glucose; SGLT-2; Type 2 diabetes