GLP-1 Agonists Decreased MACE and CV Death in Type 2 Diabetes

The association between GLP-1 RA therapy and cardiovascular outcomes in type 2 diabetes was assessed.

Patients with type 2 diabetes (T2D) who were treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA) had significantly fewer instances of major adverse cardiovascular events (MACE), cardiovascular death, and nonfatal stroke. These findings were published in the The American Journal of Cardiology.

Researchers from Penn State Hershey Medical Center searched publication databases through December 2020 for randomized, double-blind, placebo-controlled clinical trials evaluating GLP-1 RA therapy in patients with T2D. The association between GLP-1 RA therapy and cardiovascular outcomes were assessed.

A total of 7 trials comprising 56,004 patients over a follow-up period of 174,163 patient-years were included in this analysis. Patients ranged in age between an average of 60.3±9.7-66.2±6.5 years, women made up between 30.6%-46.3% of the study populations, BMI was between 30.2±5.7-32.8±6.2 kg/m2, and glycated hemoglobin ranged between 7.3%±1.1%-8.7%±1.6%.

The study drugs included 30 or 50 mg/week albiglutide, 1.5 mg/week dulaglutide, 2 mg/week exenatide, 1.8 mg/day liraglutide, 20 mg/day lixisenatide, 0.5 or 1.0 mg/week semaglutide, or 14 mg/day semaglutide. All drugs were delivered via subcutaneous injections except for the daily semaglutide which was administered orally.

GLP-1 RA therapies were associated with significantly reduced MACE (rate ratio [RR], 0.887; 95% CI, 0.829-0.949; P =.001), cardiovascular deaths (RR, 0.879; 95% CI, 0.812-0.952; P =.001), and nonfatal strokes (RR, 0.850; 95% CI, 0.765-0.946; P =.003) but not nonfatal myocardial infarctions (RR, 0.911; 95% CI, 0.815-1.018; P =.099).

The significantly associated outcomes did not include significant study heterogeneity (all P ³0.11) but the nonfatal myocardial infarction comparison did (I2, 53%; P =.05).

Although not statistically significant overall, the study authors observed a linear relationship between glycated hemoglobin at baseline with the effect of GLP-1 RA on reducing nonfatal myocardial infarction (regression coefficient, -0.179; 95% CI, -0.035 to -0.00063; R2, 0.64), indicating that GLP-1 RA therapy had a greater effect as the study population glycated hemoglobin increased.

This analysis was limited by the varying inclusion and exclusion criteria of the underlying studies with regard to cardiovascular disease risk factors, resulting in a highly heterogenous study population.

These data indicated that patients with T2D may have decreased MACE, cardiovascular death, and nonfatal stroke risk from therapy with GLP-1 RA.


Grewal S, Zaman N, Borgatta L, Nudy M, Foy AJ, Peterson B. Usefulness of Glucagon-Like Peptide-1 Receptor Agonists to Reduce Adverse Cardiovascular Disease Events in Patients with Type 2 Diabetes Mellitus. Am J Cardiol. 2021;154:48-53.