Comparative cardiovascular safety of glucagon‐like peptide‐1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study

Mar 23, 2016Diabetes, obesity & metabolism

Heart safety of glucagon-like peptide-1 drugs compared to other diabetes medicines in everyday use

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Abstract

During 1 year, there were 13.9 cardiovascular disease (CVD) events per 1000 person-years among initiators of GLP-1 receptor agonists compared to 13.7 events for DPP-4 inhibitors.

No significant difference in CVD events was observed when comparing GLP-1 receptor agonists to DPP-4 inhibitors (hazard ratio 1.02).
Initiators of GLP-1 receptor agonists experienced fewer CVD events compared to those starting sulphonylureas (12.1 vs. 14.0 events, hazard ratio 0.86).
The comparison between GLP-1 receptor agonists and insulin showed results sensitive to adjustments for blood sugar levels, with a hazard ratio of 1.01.
The findings were consistent across various sensitivity analyses, including a long-term follow-up of up to 8.7 years.
The study provides insights into the relative safety of GLP-1 receptor agonists in a real-world population of patients with type 2 diabetes.

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AIMS: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM).

METHODS: Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i.e. DPP-4 inhibitor (n = 35 534), second-generation sulphonylureas (n = 28 138) or insulin (n = 47 068), between 2005 and 2013. We examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization.

RESULTS: During the course of 1 year, there were 13.9 and 13.7 CVD events per 1000 person-years among propensity-score-matched initiators of GLP-1 RAs versus DPP-4 inhibitors [hazard ratio (HR) 1.02; 95% confidence interval (CI) 0.84-1.24]; and 12.1 versus 14.0 events among initiators of GLP-1 RAs versus sulphonylureas (HR 0.86; 95% CI 0.69-1.08). The effect estimates for GLP-1 RAs versus insulin were sensitive to the adjustment for glycated haemoglobin, after which the HR was 1.01 (95% CI 0.73-1.41). Results were robust across several sensitivity analyses, including an as-treated analysis considering up to 8.7 years of follow-up.

CONCLUSIONS: This large study, performing head-to-head comparisons of GLP-1 RAs with other antidiabetic agents in real-world patients, provides estimates of relative safety precise enough to exclude large differences in CVD risk and adds further understanding to results from recent clinical trials.

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Comparative cardiovascular safety of glucagon‐like peptide‐1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study

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