HbA1c reduction with GLP-1RA leads to lower risk of CV events in cardiovascular outcome trials

The reduction of cardiovascular (CV) events in CV outcome trials (CVOTs) of glucagon-like peptide-1 receptor agonist (GLP-1RA) can be explained by a decrease in HbA1c.

Sodium-glucose transport protein 2 inhibitors and GLP-1RA have not only shown glycaemic benefits in several trials, but also significant positive effects on CV risk. However, variability in outcomes of better glycaemic control with GLP-1RA has cast some doubt over whether improved glycaemic control mediated CV risk reduction with these agents.

Dr Mart Roosimaa (University of Tartu, Estonia) and colleagues performed a meta-analysis to determine whether better glycaemic control was responsible for the GLP-1RA-mediated reduction in CV risk [1]. HbA1c levels were used as an indicator of glycaemic control, and for the primary outcome of absolute CV risk, the number of patients at risk was extracted for both GLP-1RA and placebo groups at multiple time points from each published GLP-1RA trial. The cumulative glycaemic exposure was calculated separately for the placebo and GLP-1RA groups in each trial and correlated with observed absolute CV risk. Differential glycaemic exposure between the GLP-1RA and placebo group was calculated for each trial and correlated with the published hazard ratio (HR).

A linear correlation between increased HbA1c and CV risk with both GLP-1RA and placebo was observed. The placebo group appeared to have lower absolute risk for the same glycaemic exposure. However, this difference disappeared after correction for patient age. There was a strong correlation between the difference in glycaemic exposure of the GLP-1RA group compared with the placebo group and the reported HR. The 95% confidence intervals of the HRs from all trials supported the hypothesis that the risk reduction could be attributed to differences in HbA1c. Lowering the HbA1c by 1% decreased CV risk by 30%; this relationship was consistent within the placebo and the GLP-1RA groups and between groups.

1. Roosimaa M & Jõgis A. Reduction of cardiovascular events by GLP-1 receptor agonists is explained by HbA1c reduction. EASD 2020. Abstract #147.

Posted on 14 December, 202027 March, 2024