SAVOR-TIMI to DECLARE-TIMI: A review on cardiovascular outcome trials of incretin-modulators and gliflozins

SAVOR-TIMI to DECLARE-TIMI: A review on cardiovascular outcome trials of incretin-modulators and gliflozins

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Introduction: Since 2008 United State (US) food drug administration mandate, several newer anti-diabetic drugs (ADD) have undergone a mandatory cardiovascular (CV) outcome trial (CVOT) in type diabetes (T2DM) patients with high CV risk.These includes CVOT done with dipeptidyl-peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors and glucagon-like here peptide-1 receptor agonist (GLP-1RAs).Several double-blind, randomized, placebo-controlled CVOT have been presented and published in the last decade (2008-2018).

Aims and Objectives: We systematically searched the database of PubMed and ClinicalTrials.gov from January 1, 2008 to December 31, 2018 using specific key words.Subsequently, we pooled the data of different cardiovascular endpoints and made a comparative forest plot using GraphPad software Inc.

Prism Version 8, US.Results and Conclusion: Saxagliptin, alogliptin, sitagliptin and linagliptin are CV neutral drugs.Saxagliptin showed a significantly higher hospitalization due to heart failure (HHF).

Empagliflozin and canagliflozin have shown a significant reduction in composite of 3-point major cardiac adverse events (3P-MACE).Additionally, empagliflozin, canagliflozin and dapagliflozin significantly reduced the HHF and the composite of CV death or HHF.Moreover, empagliflozin showed significant reduction in CV- and all-cause death in patients with T2DM with established CV disease.

While both exendin-backbone-based GLP-1RAs such as lixisenatide and extended-release exenatide were CV neutral; GLP-1-backbone-based GLP-1RAs such as liraglutide, semaglutide and albiglutide shown a significant reduction in us polo assn mens sweaters the composite of 3-P MACE.Additionally, liraglutide shown a significant reduction in CV- and all-cause death.Moreover, semaglutide reduced non-fatal stroke and albiglutide reduced myocardial infarction, while extended-release exenatide reduced all-cause death; however, P value of significance for these outcomes should be considered nominal.