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

Overview

Journal J Diabetes Res

Publisher Wiley

Specialty Endocrinology

Date 2021 Jul 14

PMID 34258291

Citations 9

Authors

Habib Yaribeygi

Farin Rashid Farrokhi

Mohammed Altigani Abdalla

Thozhukat Sathyapalan

Maciej Banach

Tannaz Jamialahmadi

Amirhossein Sahebkar

Affiliations

Soon will be listed here.

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 -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.

Citing Articles

Microvascular Dysfunction Following Cardioplegic Arrest and Cardiopulmonary Bypass: Impacts of Diabetes and Hypertension.

Kanuparthy M, Manthana R, Kaushik H, Xiang K, Hamze J, Marimekala D Biomedicines. 2025; 13(2).

PMID: 40002822 PMC: 11853148. DOI: 10.3390/biomedicines13020409.

Unexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study.

Lin C, Chen J, Meyerowitz-Katz G, Huang Y, Su P Diabetes Obes Metab. 2025; 27(4):1980-1991.

PMID: 39806559 PMC: 11885080. DOI: 10.1111/dom.16191.

A Specific Collagen Hydrolysate Improves Postprandial Glucose Tolerance in Normoglycemic and Prediabetic Mice and in a First Proof of Concept Study in Healthy, Normoglycemic and Prediabetic Humans.

Grasset E, Briand F, Virgilio N, Schon C, Wilhelm M, Cudennec B Food Sci Nutr. 2024; 12(11):9607-9620.

PMID: 39619994 PMC: 11606891. DOI: 10.1002/fsn3.4538.

Recent Advances and Therapeutic Benefits of Glucagon-Like Peptide-1 (GLP-1) Agonists in the Management of Type 2 Diabetes and Associated Metabolic Disorders.

Olukorode J, Orimoloye D, Nwachukwu N, Onwuzo C, Oloyede P, Fayemi T Cureus. 2024; 16(10):e72080.

PMID: 39574978 PMC: 11579408. DOI: 10.7759/cureus.72080.

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

Jalil J, Gabrielli L, Ocaranza M, MacNab P, Fernandez R, Grassi B Int J Mol Sci. 2024; 25(8).

PMID: 38673991 PMC: 11049921. DOI: 10.3390/ijms25084407.

References

Kuniss N, Freyer M, Muller N, Kielstein V, Muller U . Expectations and fear of diabetes-related long-term complications in people with type 2 diabetes at primary care level. Acta Diabetol. 2018; 56(1):33-38. DOI: 10.1007/s00592-018-1217-9. View

Bian K, Doursout M, Murad F . Vascular system: role of nitric oxide in cardiovascular diseases. J Clin Hypertens (Greenwich). 2008; 10(4):304-10. PMC: 8109995. DOI: 10.1111/j.1751-7176.2008.06632.x. View

Marney A, Kunchakarra S, Byrne L, Brown N . Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans. Hypertension. 2010; 56(4):728-33. PMC: 3305047. DOI: 10.1161/HYPERTENSIONAHA.110.156554. View

Romacho T, Vallejo S, Villalobos L, Wronkowitz N, Indrakusuma I, Sell H . Soluble dipeptidyl peptidase-4 induces microvascular endothelial dysfunction through proteinase-activated receptor-2 and thromboxane A2 release. J Hypertens. 2016; 34(5):869-76. DOI: 10.1097/HJH.0000000000000886. View

Gardiner S, March J, Kemp P, Bennett T . Mesenteric vasoconstriction and hindquarters vasodilatation accompany the pressor actions of exendin-4 in conscious rats. J Pharmacol Exp Ther. 2005; 316(2):852-9. DOI: 10.1124/jpet.105.093104. View

Howard B, Roman M, Devereux R, Fleg J, Galloway J, Henderson J . Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial. JAMA. 2008; 299(14):1678-89. PMC: 4243925. DOI: 10.1001/jama.299.14.1678. View

Liu L, Liu J, Huang Y . Protective Effects of Glucagon-like Peptide 1 on Endothelial Function in Hypertension. J Cardiovasc Pharmacol. 2014; 65(5):399-405. DOI: 10.1097/FJC.0000000000000176. View

Liu J, Yin F, Zheng X, Jing J, Hu Y . Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. Neurochem Int. 2007; 51(6-7):361-9. DOI: 10.1016/j.neuint.2007.04.021. View

Garber A, Henry R, Ratner R, Garcia-Hernandez P, Rodriguez-Pattzi H, Olvera-Alvarez I . Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2008; 373(9662):473-81. DOI: 10.1016/S0140-6736(08)61246-5. View

10.

Lovshin J, Barnie A, DeAlmeida A, Logan A, Zinman B, Drucker D . Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes. Diabetes Care. 2014; 38(1):132-9. DOI: 10.2337/dc14-1958. View

11.

Woo J, Kim W, Ha S, Kim J, Kim S, Kim W . Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study. Arterioscler Thromb Vasc Biol. 2013; 33(9):2252-60. DOI: 10.1161/ATVBAHA.113.301586. View

12.

Hernandez A, Green J, Janmohamed S, DAgostino Sr R, Granger C, Jones N . Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018; 392(10157):1519-1529. DOI: 10.1016/S0140-6736(18)32261-X. View

13.

ONeal K, Johnson J, Panak R . Recognizing and Appropriately Treating Latent Autoimmune Diabetes in Adults. Diabetes Spectr. 2016; 29(4):249-252. PMC: 5111528. DOI: 10.2337/ds15-0047. View

14.

Lee M, Tsai K, Hsu J, Shin S, Wu J, Yeh J . Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways. Sci Rep. 2016; 6:31788. PMC: 5007506. DOI: 10.1038/srep31788. View

15.

Cosenso-Martin L, Giollo-Junior L, Barufi Fernandes L, Cesarino C, Arruda Nakazone M, Machado M . Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial. Acta Diabetol. 2018; 55(12):1237-1245. DOI: 10.1007/s00592-018-1204-1. View

16.

Papaetis G . Incretin-based therapies in prediabetes: Current evidence and future perspectives. World J Diabetes. 2014; 5(6):817-34. PMC: 4265868. DOI: 10.4239/wjd.v5.i6.817. View

17.

Russell-Jones D, Vaag A, Schmitz O, Sethi B, Lalic N, Antic S . Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia. 2009; 52(10):2046-55. PMC: 2744824. DOI: 10.1007/s00125-009-1472-y. View

18.

Koren S, Shemesh-Bar L, Tirosh A, Peleg R, Berman S, Hamad R . The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients. Diabetes Technol Ther. 2012; 14(7):561-7. DOI: 10.1089/dia.2011.0296. View

19.

Skov J, Dejgaard A, Frokiaer J, Holst J, Jonassen T, Rittig S . Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men. J Clin Endocrinol Metab. 2013; 98(4):E664-71. DOI: 10.1210/jc.2012-3855. View

20.

Bergenstal R . Glycemic Variability and Diabetes Complications: Does It Matter? Simply Put, There Are Better Glycemic Markers!. Diabetes Care. 2015; 38(8):1615-21. DOI: 10.2337/dc15-0099. View