The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptydilpeptidase-4 Inhibitors on Blood Pressure and Cardiovascular Complications in Diabetes

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of newly introduced antidiabetic medications that potentially lower blood glucose by several molecular pathways. DPP-4 inhibitors are the other type of novel antidiabetic medications which act by preventing GLP-1 inactivation and thereby increasing the activity levels of GLP-1, leading to more glucose-induced insulin release from islet β-cells and suppression of glucagon release. Most patients with diabetes have concurrent hypertension and cardiovascular disorder. If antihyperglycemic agents can attenuate the risk of hypertension and cardiovascular disease, they will amplify their overall beneficial effects. There is conflicting evidence on the cardiovascular benefits of GLP-1R induction in laboratory studies and clinical trials. In this study, we have reviewed the main molecular mechanisms by which GLP-1R induction may modulate the cardiovascular function and the results of cardiovascular outcome clinical trials.

The effect of glucagon‐like peptide‐1 receptor agonists on serum uric acid concentration: A systematic review and meta‐analysis

“…Since their first approval in 2005, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have been widely prescribed for type 2 diabetes mellitus (T2DM) and obesity 1 . Their promising results in glycaemic control and weight loss, together with a low risk of inducing hypoglycaemia and a favourable cardiovascular and renal safety profile, have made them desirable therapies for the treatment of T2DM as well as its comorbidities and complications 2–8 . Since their introduction, several different formulations of these antidiabetic agents have been brought to market; to date, seven injectable analogues (twice‐daily exenatide immediate‐release, once‐weekly exenatide extended‐release, once‐daily liraglutide, once‐daily lixisenatide, once‐weekly albiglutide [currently off‐market due to a decline in sales], once‐weekly dulaglutide and once‐weekly semaglutide) and one orally‐administered analogue (once‐daily semaglutide) have been approved by the Food and Drug Administration (FDA) 9 .…”

“…1 Their promising results in glycaemic control and weight loss, together with a low risk of inducing hypoglycaemia and a favourable cardiovascular and renal safety profile, have made them desirable therapies for the treatment of T2DM as well as its comorbidities and complications. [2][3][4][5][6][7][8] Since their introduction, several different formulations of these antidiabetic agents have been brought to market; to date, seven injectable analogues (twicedaily exenatide immediate-release, once-weekly exenatide extendedrelease, once-daily liraglutide, once-daily lixisenatide, once-weekly albiglutide [currently off-market due to a decline in sales], onceweekly dulaglutide and once-weekly semaglutide) and one orallyadministered analogue (once-daily semaglutide) have been approved by the Food and Drug Administration (FDA). 9 Besides GLP-1 receptor as their putative target, numerous molecular targets have been identified for GLP-1 RAs, [10][11][12][13][14][15][16][17][18][19] which justifies their potential for wider medical applications.…”

Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease

“…DPP-IV inhibitors or gliptins, a new family of hypoglycemic medicines, increase the production of GLP-1 by inhibiting its deactivation and enhancing its action. As a result, glucagon release is reduced, and more glucose-induced insulin is secreted by islet cells [ 57 ]. DPP-IV inhibition possibly leads to the formation of Akt/endothelial NO synthase (eNOS), resulting in increased formation of NO and enhancement of fibroblast growth factor 2 (FGF-2)/early growth response protein 1 (EGR-1)/vascular endothelial growth factor A (VEGF-A) signaling [ 58 ].…”

Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?

“…Endothelial cells play a key role in BP control. GLP-1RAs stimulate acetylcholine-induced vasodilation and promote nitric oxide release, thus reducing vascular tone with benefits to both systolic and diastolic BP [44]. A recent study demonstrated that acute pharmacological stimulation of GLP-1R increases eGFR by promoting diuresis and natriuresis through the inhibition of the major renal proximal tubule sodium reabsorption pathway.…”