Abstract
BackgroundCardiovascular outcome trials in high-risk patients showed that some GLP-1 receptor agonists (GLP-1RA), but not dipeptidyl-peptidase-4 inhibitors (DPP-4i), can prevent cardiovascular events in type 2 diabetes (T2D). Since no trial has directly compared these two classes of drugs, we performed a comparative outcome analysis using real-world data.MethodsFrom a database of ~ 5 million people from North-East Italy, we retrospectively identified initiators of GLP-1RA or DPP-4i from 2011 to 2018. We obtained two balanced cohorts by 1:1 propensity score matching. The primary outcome was the 3-point major adverse cardiovascular events (3P-MACE; a composite of death, myocardial infarction, or stroke). 3P-MACE components and hospitalization for heart failure were secondary outcomes.ResultsFrom 330,193 individuals with T2D, we extracted two matched cohorts of 2807 GLP-1RA and 2807 DPP-4i initiators, followed for a median of 18 months. On average, patients were 63 years old, 60% male; 15% had pre-existing cardiovascular disease. The rate of 3P-MACE was lower in patients treated with GLP-1RA compared to DPP4i (23.5 vs. 34.9 events per 1000 person-years; HR: 0.67; 95% C.I. 0.53–0.86; p = 0.002). Rates of myocardial infarction (HR 0.67; 95% C.I. 0.50–0.91; p = 0.011) and all-cause death (HR 0.58; 95% C.I. 0.35–0.96; p = 0.034) were lower among GLP-1RA initiators. The as-treated and intention-to-treat approaches yielded similar results.ConclusionsPatients initiating a GLP-1RA in clinical practice had better cardiovascular outcomes than similar patients who initiated a DPP-4i. These data strongly confirm findings from cardiovascular outcome trials in a lower risk population.
Highlights
Cardiovascular outcome trials in high-risk patients showed that some GLP-1 receptor agonists (GLP1RA), but not dipeptidyl-peptidase-4 inhibitors (DPP-4i), can prevent cardiovascular events in type 2 diabetes (T2D)
The REWIND study, conducted on patients with T2D, 70% of whom were free from established cardiovascular disease, found that the glucagon-like peptide-1 receptor agonists (GLP-1RA) dulaglutide reduced major adverse cardiovascular events (MACE) rates compared to placebo [9]
GLP-1RA were distributed as follows: 43% liraglutide, 18% exenatide, 35% dulaglutide, 4% lixisenatide; DPP-4i were distributed as follows: 45% sitagliptin, 23% vildagliptin, 14% alogliptin, 16% linagliptin, 2% saxagliptin
Summary
Cardiovascular outcome trials in high-risk patients showed that some GLP-1 receptor agonists (GLP1RA), but not dipeptidyl-peptidase-4 inhibitors (DPP-4i), can prevent cardiovascular events in type 2 diabetes (T2D). Results of cardiovascular outcome trials (CVOTs) prompted recommendations to prioritize two classes of glucose lowering. Treatment with liraglutide, semaglutide, or albiglutide reduced the risk of MACE [5,6,7] In view of these strong benefits, the European Society of Cardiology guidelines have suggested that GLP-1RA may be recommended even as first-line in patients with T2D and established cardiovascular disease [8]. The REWIND study, conducted on patients with T2D, 70% of whom were free from established cardiovascular disease, found that the GLP-1RA dulaglutide reduced MACE rates compared to placebo [9]. It is possible that the protective effects of GLP-1RA extend to T2D patients with a relatively lower cardiovascular risk
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