Generic placeholder image

Current Hypertension Reviews

Editor-in-Chief

ISSN (Print): 1573-4021
ISSN (Online): 1875-6506

General Review Article

Cardiovascular Effects of Liraglutide

Author(s): Nasser Mikhail*

Volume 15, Issue 1, 2019

Page: [64 - 69] Pages: 6

DOI: 10.2174/1573402114666180507152620

Price: $65

Abstract

Background: Liraglutide is a glucagon-like 1 (GLP-1) agonist approved for treatment of type 2 diabetes and obesity.

Objective: To review the cardiovascular effects of liraglutide including macrovascular and microvascular events, its use in heart failure, and its effects on heart rate and blood pressure.

Results: The impact of liraglutide on cardiovascular outcomes was examined in a large welldesigned study published in 2016, the LEADER trial. This study included 9,340 patients with advanced type 2 diabetes and high baseline cardiovascular risk. The primary outcome was the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 3.8 years, patients randomized to liraglutide had significant reduction in the composite primary outcome compared to patients randomized to placebo, hazard ratio (HR) 0.87; 95% CI 0.78-0.97. Death from cardiovascular causes was significantly reduced with liraglutide therapy (HR, 0.78; 95% CI 0.66-0.93), as well as death from any cause (HR, 0.85; 95% CI 0.74-0.97). In 2017, the LEADER investigators reported that nephropathy events were significantly lower after liraglutide therapy than placebo (HR 0.78; 95% CI 0.67-0.92), but there was no significant difference in retinopathy events. Meanwhile, other studies suggested that the use of liraglutide may be harmful in patients with severe heart failure, in part due to increase in heart rate.

Conclusion: Liraglutide is a useful therapy in patients with advanced type 2 diabetes complicated by cardiovascular disease, except patients with severe heart failure. Further studies are needed to evaluate the long-term effects of liraglutide, and to see whether its beneficial effects extend to patients with type 2 diabetes and low cardiac risk.

Keywords: Liraglutide, cardiovascular events, nephropathy, heart failure, heart rate, blood pressure.

[1]
Victoza (Liraglutide) Prescribing information Novo Nordisk Inc Plainsboro, NJ, USA, August 25, 2017
[2]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee:LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375(4): 311-22.
[3]
Rizzo M, Chandalia M, Patt AM, et al. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol 2014; 13(49): 1-5.
[4]
Li J, Liu X, Fang Q, et al. Liraglutide attenuates atherosclerosis via inhibiting ER-induced macrophage derived microvesicles production in T2DM rats. Diabetol Metab Syndr 2017; 9(94): 1-8.
[5]
Shi L, Ji Y, Jiang X, et al. Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK 1/2 and PI3K/Akt signaling pathways. Cardiovasc Diabetol 2015; 14(18): 1-13.
[6]
Mann JFE, Orsted DD, Brown-Frendson K, et al. , for the LEADER Steering Committee and investigatorsLiraglutide and renal outcomes in type 2 diabetes. N Engl J Med 2017; 377(9): 839-48.
[7]
Marso SP, Bain SC, Consoli A, et al. for the SUSTAIN-6 Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375(19): 1834-44.
[8]
Hillis GS, Hata J, Woodward M, et al. Resting heart rate and the risk of microvascular complications in patients with type 2 diabetes mellitus. J Am Heart Assoc 2012; 1(5): e002832.
[9]
Zhang JY, Wang XY, Wang X. Effects of liraglutide on hemodynamic parameters in patients with heart failure. Oncotarget 2017; 8(37): 62693-702.
[10]
Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)- a multicenter, double-blind, randomized, placebo-controlled trial. Eur J Heart Fail 2017; 19: 69-77.
[11]
Dobre D, Borer JS, Fox K, et al. Heart rate: a prognostic factor and therapeutic target in chronic heart failure. The distinct roles of drugs with heart rate-lowering properties. Eur J Heart Fail 2014; 16: 76-85.
[12]
Margulies KB, Hernandez AF, Redfield MM, et al. for the NHLBI Heart Failure Clinical Research Network.Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction. A randomized clinical trial. JAMA 2016; 316(5): 500-8.
[13]
Lorenz M, Lawson F, Owens D, et al. Differential effects of glucagon-like peptide receptor agonists on heart rate. Cardiovasc Diabetol 2017; 16(6): 1-10.
[14]
Kumarathurai P, Anholm C, Fabricius-Bjerre A, et al. Effects of the glucagon-like peptide-1 receptor agonist liraglutide on 24-hambulatory blood pressure in patients with type 2 diabetes and stable coronary artery disease: a randomized, double-blind, placebo-controlled crossover study. J Hypertens 2017; 35(5): 1070-8.
[15]
Nakatani Y, Kawabe AQ, Matsumara M, et al. Effects of GLP-1 receptor agonists on heart rate and the autonomic nervous system using Holter electrocardiography and power spectrum analysis of heart rate variability. Diabetes Care 2016; 39: e22-3.
[16]
Pyke C, Heller RS, Kirk PK, et al. GLP-1 receptor localization in monkey and human tissue: Novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 2014; 255: 1280-90.
[17]
Cooney MT, Vartiainen E, Laatikainen T, et al. Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. Am Heart J 2010; 159: 612-9.
[18]
Hillis GS, Woodward M, Rodgers A, et al. Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus. Diabetologia 2012; 55: 1283-90.
[19]
Lovshin JA, Barnie A, DeAlmeida A, et al. Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes. Diabetes Care 2015; 38: 132-9.
[20]
Pfeffer MA, Claggett B, Diaz R, et al. for the ELIXA Investigators,Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 2015; 373(23): 2247-57.
[21]
Holman RR, Bethel MA, Mentz RJ, et al. for the EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377(13): 1228-39.
[22]
American Diabetes Association,Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018; 41(Suppl. 1): S73-85.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy