Elsevier

The American Journal of Cardiology

Volume 154, 1 September 2021, Pages 48-53
The American Journal of Cardiology

Usefulness of Glucagon-Like Peptide-1 Receptor Agonists to Reduce Adverse Cardiovascular Disease Events in Patients with Type 2 Diabetes Mellitus

https://doi.org/10.1016/j.amjcard.2021.05.043Get rights and content

Evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular disease (CVD) events. The objective of this study was to analyze randomized controlled trials (RCT) testing GLP-1 RA's effect on CVD events among participants with type 2 diabetes (T2DM). RCTs comparing GLP-1 RA versus placebo were identified using the PubMed and Cochrane databases. The endpoints in this study included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi2 and I2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using mean baseline hemoglobin A1C (A1C) as the moderator and a R2 value was calculated. Seven RCTs (N = 56,004) were identified with 174,163 patient-years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83 to 0.95], cardiovascular death [RR 0.88, 95% CI 0.81 to 0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77 to 0.95]. There was no statistically significant heterogeneity among these RCTs. GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.81 to 1.02]. However, there was significant heterogeneity among these RCTs (Chi2 = 12.68, p = 0.05, I2 = 53%). When accounting for baseline A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p = 0.23, I2 = 27%). A potential linear relationship between baseline A1C and GLP-1 RA's effect on nonfatal MI (R2 = 0.64) was observed. In conclusion, GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke; GLP-1 RA did not reduce nonfatal MI, however there may be a linear association between baseline A1C and GLP-1 RA's effect on nonfatal MI.

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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