Glucagon-like Peptide-1 Receptor Agonists Cardio-protective Effects: An Umbrella Review

Author(s): Asim Ahmed Elnour*, Noora Al Hajri, Israa Yousif El Khidir, Abdulla AlAmoodi, Sahar Asim Ahmed, Adel Sadeq

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 8 , 2020


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Abstract:

Background: We thought to delve deeper into seven meta-analyses of major clinical trials focusing on Glucagon-Like Peptide-One Receptor Agonist (GLP-1 RA) cardioprotective effect.

Aim: We explored the role of GLP-1 RA in cardiovascular risk protection as the primary outcome in subjects with type 2 diabetes mellitus.

Methodology: The current review has explored and critically appraised seven meta-analyses of placebo- controlled randomized clinical trials (RCT-s) involving GLP-1 RA used in diabetes that has exhibited major cardiovascular events as the primary outcome.

Results: Based on the participants-intervention-comparison and outcomes (PICO), the total number of the participants in this review were (138750), the intervention was conducted with GLP-1 RA, the comparator was a placebo and the outcome was major cardiovascular events. The overall evidence for the cardioprotective effect of GLP-1 RA in diabetes was very clear in subjects with the cardiovascular risk of varying degrees. Most of the currently reviewed meta-analyses have not shown cardioprotection with GLP-1 RA in subjects with diabetes exhibiting high cardiovascular risk or medical history of cardiovascular diseases. Patient variability, in addition to potency parameters, will be the key to a successful member of the class. There will be avenues for selection of a candidate based on the suitability to patient preferences and characteristics.

Conclusion: The RCT-s for GLP-1 RA should characterize cardiovascular risk in subjects with diabetes such that disparities between established cardiovascular risk (high, moderate and low) or medical history of cardiovascular disease have been accounted for in subgroup analysis.

Keywords: Cardiovascular Diseases (CVD), Glucagon-like Peptide 1 Receptor Agonist (GLP-1 RA), Major Adverse Cardiovascular Events (MACE), meta-analysis, Type 2 Diabetes Mellitus (T2DM).

[1]
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15): 1577-89.
[http://dx.doi.org/10.1056/NEJMoa0806470] [PMID: 18784090]
[2]
Holman RR, Paul SK, Bethel MA, Neil HAW, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 2008; 359(15): 1565-76.
[http://dx.doi.org/10.1056/NEJMoa0806359] [PMID: 18784091]
[3]
The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes N Engl J Med 2008; 358 2560e72
[4]
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes N Engl J Med 2009; 360 129e39
[5]
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.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[6]
Marso SP, Bain SC, Consoli A, et al. SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375(19): 1834-44.
[http://dx.doi.org/10.1056/NEJMoa1607141] [PMID: 27633186]
[7]
Pfeffer MA, Claggett B, Diaz R, et al. ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 2015; 373(23): 2247-57.
[http://dx.doi.org/10.1056/NEJMoa1509225] [PMID: 26630143]
[8]
Holman RR, Bethel MA, Mentz RJ, et al. EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377(13): 1228-39.
[http://dx.doi.org/10.1056/NEJMoa1612917] [PMID: 28910237]
[9]
Gerstein HC, Colhoun HM, Dagenais GR, et al. REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019; 394(10193): 121-30.
[http://dx.doi.org/10.1016/S0140-6736(19)31149-3] [PMID: 31189511]
[10]
Lorenz M, Lawson F, Owens D, et al. Differential effects of glucagon-like peptide-1 receptor agonists on heart rate. Cardiovasc Diabetol 2017; 16(1): 6.
[http://dx.doi.org/10.1186/s12933-016-0490-6] [PMID: 28086882]
[11]
Mora PF, Johnson EL. Cardiovascular outcome trials of the incretin-based therapies: What do we know so far? Endocr Pract 2017; 23(1): 89-99.
[http://dx.doi.org/10.4158/EP161481.RA] [PMID: 27819769]
[12]
Al Yami MS, Alfayez OM, Alsheikh R. Update in cardiovascular safety of glucagon like peptide-1 receptor agonists in patients with type 2 diabetes A mixed treatment comparison meta-analysis of randomised controlled trials Heart. Lung and Circulation 2018; 27(11): 1301-9.
[13]
Wang Q, Liu L, Gao L, Li Q. Cardiovascular safety of GLP-1 receptor agonists for diabetes patients with high cardiovascular risk: A meta-analysis of cardiovascular outcomes trials. Diabetes Res Clin Pract 2018; 143: 34-42.
[http://dx.doi.org/10.1016/j.diabres.2018.06.009] [PMID: 29935211]
[14]
Jia X, Alam M, Ye Y, Bajaj M, Birnbaum Y. GLP-1 receptor agonists and cardiovascular disease: a meta-analysis of recent cardiac outcome trials. Cardiovasc Drugs Ther 2018; 32(1): 65-72.
[http://dx.doi.org/10.1007/s10557-018-6773-2] [PMID: 29445896]
[15]
Bethel MA, Patel RA, Merrill P, et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. The lancet Diabetes and Endocrinology 2018; 6(2): 105-13.
[http://dx.doi.org/10.1016/S2213-8587(17)30412-6]
[16]
Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E. Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2014; 16(1): 38-47.
[http://dx.doi.org/10.1111/dom.12175] [PMID: 23829656]
[17]
Sun F, Yu K, Wu S, et al. Cardiovascular safety and glycemic control of glucagon-like peptide-1 receptor agonists for type 2 diabetes mellitus: a pairwise and network meta-analysis. Diabetes Res Clin Pract 2012; 98(3): 386-95.
[http://dx.doi.org/10.1016/j.diabres.2012.09.004] [PMID: 23020934]
[18]
Monami M, Cremasco F, Lamanna C, Colombi C, Desideri CM, Iacomelli I, et al. Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Experiment Diab Res 2011.
[19]
Giugliano D, Maiorino MI, Longo M, Bellastella G, Chiodini P, Esposito K. Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials. Endocrine 2019; 65(1): 15-24.
[http://dx.doi.org/10.1007/s12020-019-01931-y] [PMID: 31028667]
[20]
Alfayez OM, Al Yami MS, Alshibani M, et al. Network meta-analysis of nine large cardiovascular outcome trials of new antidiabetic drugs. Prim Care Diabetes 2019; 13(3): 204-11.
[http://dx.doi.org/10.1016/j.pcd.2019.01.003] [PMID: 30713085]
[21]
Mannucci E, Monami M. Cardiovascular safety of incretin-based therapies in type 2 diabetes: systematic review of integrated analyses and randomized controlled trials. Adv Ther 2017; 34(1): 1-40.
[http://dx.doi.org/10.1007/s12325-016-0432-4] [PMID: 27844335]
[22]
Seshasai SR, Bennett RL, Petrie JR, et al. Cardiovascular safety of the glucagon-like peptide-1 receptor agonist taspoglutide in people with type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. Diabetes Obes Metab 2015; 17(5): 505-10.
[http://dx.doi.org/10.1111/dom.12448] [PMID: 25656522]
[23]
American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care 2019; 42(Suppl. 1): S90-S102.
[http://dx.doi.org/10.2337/dc19-S009] [PMID: 30559235]
[24]
Jendle J, Grunberger G, Blevins T, Giorgino F, Hietpas RT, Botros FT. Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program. Diabetes Metab Res Rev 2016; 32(8): 776-90.
[http://dx.doi.org/10.1002/dmrr.2810] [PMID: 27102969]


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Article Details

VOLUME: 16
ISSUE: 8
Year: 2020
Page: [820 - 832]
Pages: 13
DOI: 10.2174/1573399816666200522214554
Price: $65

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