Primary care diabetesDec 26, 2021

Heart benefits of glucagon-like peptide 1 receptor drugs compared to dipeptidyl peptidase-4 inhibitors in type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

GLP-1 receptor agonists (GLP-1RA) are associated with a 76% lower risk of major adverse cardiovascular events compared to DPP-4 inhibitors (DPP-4i) in patients with type 2 diabetes.

GLP-1RA is linked to significantly lower risks of cardiovascular mortality (HR 0.59) and myocardial infarction (HR 0.89).
The risk of stroke is also reduced with GLP-1RA (HR 0.86) compared to DPP-4i.
All-cause mortality is decreased with GLP-1RA use (HR 0.63).
Both drug classes show similar risks for hospitalization due to heart failure (HR 0.95).
Meta-regression analysis indicates that several factors, including age and sex, do not significantly influence the effectiveness of GLP-1RA.

Simplified

Glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are two novel classes of hypoglycemic agents. The relative cardiovascular effectiveness between these two drug classes in patients with type 2 diabetes (T2D) is unestablished due to the absence of large cardiovascular outcome trials directly comparing DPP-4i with GLP-1RA. We aimed to incorporate large propensity score-matched cohort studies to conduct a meta-analysis, to determine the relative effectiveness of GLP-1RA versus DPP-4i on cardiovascular endpoints in T2D patients. Compared to DPP-4i, GLP-1RA was associated with the significantly lower risks of major adverse cardiovascular events [MACE] (HR 0.76, 95% CI 0.63-0.92), cardiovascular mortality (HR 0.59, 95% CI 0.37-0.95), myocardial infarction (HR 0.89, 95% CI 0.80-0.98), stroke (HR 0.86, 95% CI 0.76-0.96), and all-cause mortality (HR 0.63, 95% CI 0.42-0.96) in T2D patients; whereas these two drug classes had the similar risk of hospitalization for heart failure [HHF] (HR 0.95, 95% CI 0.77-1.16). Meta-regression analyses showed that six factors (i.e., mean age, female proportion, cardiovascular disease proportion, heart failure proportion, and the proportions of receiving metformin and insulin at baseline) did not significantly affect the effects of GLP-1RA on MACE and HHF (P ≥ 0.076). This meta-analysis provides the direct evidence regarding the relative cardiovascular effectiveness of GLP-1RA versus DPP-4i from real-world studies, and its findings suggest that among T2D patients GLP-1RA should be considered in preference to DPP-4i as for preventing atherosclerotic cardiovascular events and death in clinical practice.

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Heart benefits of glucagon-like peptide 1 receptor drugs compared to dipeptidyl peptidase-4 inhibitors in type 2 diabetes

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