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GLP-1 Agonist Has CV Benefits

New study shows lower risk for poor cardiovascular outcomes for T2 patients on glucagonlike peptide-1 receptor agonists.

Researchers from the Cleveland Clinic in Ohio report that glucagon-like peptide-1 receptor (GLP-1) agonists have a number of cardiovascular benefits for those with type 2 diabetes.

Patients with T2D between 2005-2015 (N = 105,862) were identified in the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1 RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes. The findings were further evaluated by assessing the effect of GLP-1 RA on the same variables in patients with and without prior CVD. The model adjusted for differences in demographic information, hypertension, lab/vitals, past history of outcomes, and T2D medications.

Eight percent of the participants had been taking GLP-1 medication, and the researchers used electronic health records to identify which patients had known cardiovascular disease and which patients didn’t.

There were significantly lower rates of AMI (hazard ratio [HR] = 0.80, P = 0.045), CVA (HR=0.82, 95% CI=0.74-0.91, P < 0.001), overall mortality (HR=0.48, 95% CI=0.41-0.57, P < 0.001), and the composite outcome (HR=0.82, 95% CI=0.74-0.91, P < 0.002) during the consolidated time that patients were exposed to GLP-1 RA compared to corresponding rates during intervals without GLP-1 RA exposure. GLP-1 RA was associated with a significant decrease in CVA, mortality, and the composite outcome in patients with and without established CVD, not significantly affecting AMI in these subgroups.

Participants on GLP-1 drugs demonstrated a significantly lower risk for stroke and all-cause mortality. When the researchers then compared patients with and without CV disease separately, GLP-1 therapy also correlated with lower risk for poor cardiovascular outcomes.

Dr. Kevin M. Pantalone, the lead author, said that while the findings are positive, there are some limitations with the study that need to be addressed in future research.

In his statement, he added that, “It is difficult to know how long the patients in our study may have had T2DM, or what medications they may have been exposed to (and for how long), prior to them entering our health system.”

In conclusion, GLP-1 RA exposure was found to be associated with a reduction in the risk of cardiovascular events observed and overall mortality among patients with T2D with and without established CVD, after adjusting for potential confounders.

Conducting additional studies using an incidence cohort of patients (i.e., those with a known date of T2DM diagnosis/duration of disease) would be helpful in determining if lower-risk CV patients with T2DM may also benefit from a CV standpoint from GLP-1 RA therapy.

In another study they compared the cardiovascular safety of the GLP-1 drugs versus other antidiabetic drugs.

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, sulfonylureas or insulin, when added to metformin, as used in ‘real-world’ patients with type 2 diabetes mellitus (T2DM).

Within a large U.S. commercial health plan database linked to laboratory test results, they 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. They examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization.

The results of the study showed that 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 sulfonylureas (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 hemoglobin, 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.

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.

Practice Pearls:

  • We now have two classes of drugs that can improve CV outcomes, GLP-1 agonists and SGLT-2 inhibitors.
  • When compared to other classes of drugs as DPP-4 inhibitors, sulfonylureas and insulin, the GLP-1 inhibitors showed a benefit that the others did not show, that was the reduction of heart attacks, strokes and death.
  • GLP-1 RA exposure was found to be associated with a reduction in the risk of cardiovascular events observed and overall mortality among patients with T2D with and without established CVD

The study was published in the journal Diabetes, Obesity and Metabolism. May 2017

Health data on the heart risks associated with several diabetes medications will be presented at the annual meeting of the American Diabetes Association on June 9.