Usefulness of Glucagon-Like Peptide-1 Receptor Agonists to Reduce Adverse Cardiovascular Disease Events in Patients with Type 2 Diabetes Mellitus
Section snippets
Methods
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) document was used as a guide and followed.12,13 Published randomized, double-blind, placebo-controlled RCT testing GLP-1 RA in adult patients with T2DM were identified. Trials that reported MACE and the individual components of it were considered for inclusion. If a trial reported MI as both fatal and nonfatal, fatal MI was included in the cardiovascular death endpoint while nonfatal MI was included in the nonfatal
Results
We identified 7 RCT (N = 56,004) that compared GLP-1 RA to placebo amongst adult patients with T2DM, which included 174,163 patient-years of follow-up (Figure 1). In chronological order of the reported results, these RCT were ELIXA (lixisenatide),5 LEADER (liraglutide),6 SUSTAIN-6 (semaglutide),7 EXSCEL (exenatide),8 HARMONY OUTCOMES (albiglutide),9 REWIND (dulaglutide),10 and PIONEER-6 (oral semaglutide)11 (Table 1). Of the 7 studies analyzed, EXSCEL and REWIND reported median and
Discussion
The main findings of the study are that GLP-1 RA reduced MACE, CV death and nonfatal stroke with minimal heterogeneity between studies. However, GLP-1 RA did not reduce nonfatal MI and there was statistically significant heterogeneity with this endpoint. Regression analysis found a potential linear relationship between mean baseline A1C and the treatment effect of GLP-1 RA on nonfatal MI. As the mean baseline A1C in the trial population increased, there was an association with a greater effect
Declaration of Interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests.
Disclosures
None.
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2022, Endocrine PracticeCitation Excerpt :ELIXA (lixisenatide vs placebo after acute coronary syndrome) showed noninferiority for MACE but no effect on fatal or nonfatal stroke.645 Two meta-analyses of CVOTs of GLP-1 RAs vs placebo reported MACE outcomes, including stroke.643,660 A 2021 meta-analysis analyzed 7 RCTs (N = 56,005 participants) with 174,163 patient years of follow-up and found that GLP-1 RAs reduced nonfatal stroke (RR, 0.85; 95% CI, 0.77-0.95) without statistically significant heterogeneity among the trials.660
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2022, Trends in Endocrinology and MetabolismCitation Excerpt :Nevertheless, the neural circuits, targets, and sites of action of peripherally administered GLP-1 RAs require further investigation regarding specific GLP-1 RAs [34,35,39,40]. Some GLP-1 RAs (dulaglutide, liraglutide, and Semaglutide injection) have been shown to reduce the risk of fatal and nonfatal cardiovascular events, including nonfatal stroke [23,37,41]. GLP-1 RAs also affect lipid homeostasis, promoting beneficial modulatory effects on lipid parameters indirectly, and data indicate direct regulation of lipid metabolism [33,42].