Exenatide Reduces Risk of MACE for Type 2 Diabetes Patients

Exenatide joins trend of GLP-1 agonists showing benefit for patients with established CVD.

Once type 2 diabetes (T2D) begins to take hold in a patient’s body, the risk of developing another disease increases exponentially. Of the list of comorbidities that can manifest, cardiovascular disease (CVD) is a diagnosis that is often seen in patients who have established type 2 diabetes. Having established diabetes and CVD puts patients at risk for Major Adverse CV Events, otherwise known by the acronym MACE. Although the criteria for MACE is different from study to study, the main 3 points of MACE include nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death. These 3 “points” are often seen in patients with a dual diagnosis of both CVD and type 2 diabetes. According to the clinical outcomes of a subgroup in the EXSCEL study, Robert J. Mentz, MD, Associate Professor of Medicine at Duke University, states that there may be a potential reduction in MACE risk for patients diagnosed with type 2 diabetes and CVD at baseline. Through the use of the once-weekly GLP-1 Agonist Exenatide, it was apparent that there was an overall reduction in MACE events in the EXSCEL subgroup.

Through the analysis of data gathered on the 10,782 participants of the EXSCEL study, around 72% of patients were found to have Coronary Artery Disease, 23% were found to have Cerebrovascular Disease, and 25% of patients had Peripheral Vascular Disease. This subgroup of the EXSCEL study comprised 73% of the total participants in the trial. The patients were separated into 2 cohorts, the first cohort being those who are injected with 2 mg of once-weekly Exenatide, and the second cohort being the placebo group. The primary endpoint of the EXSCEL trial was to measure the incidence of MACE in patients with established CVD and T2D after the follow-up period of 3.2 years.

The results of the EXSCEL trial showed promise for patients with established CVD and T2D. The overall incidence rate of MACE was found to be lower in the Exenatide cohort when compared to that of the placebo group (11.4% vs. 12.2%; HR = 0.91; 95% CI, 0.83-1; p=.061). Although the statistics do not show significance in the primary endpoint, it was found that the rate of all-cause mortality was lower in the exenatide group when compared to that of the placebo group (6.9% vs. 7.9%; HR = 0.86; 95% CI, 0.77-0.97)  it is important to note that there can be modifications done to the trial that may yield a more favorable P-value. In the subgroup of patients who had known CVD at baseline, it was found that once-weekly Exenatide reduced the Relative Risk (RR) of MACE by 10% (13.4% vs. 14.6% for placebo; HR = 0.9; 95% CI, 0.816-0.999; p=.047).

Although the lowering of the MACE incidence rate in the overall data proved not significant, it is very important that we focus on the all-cause mortality leg of the EXSCEL trial. There is significance in the lowering of the RR of MACE by 10%. Mentz goes on to say that this study is one of many studies that are trending towards the conclusion that GLP-1 agonists consistently show a benefit in those with established CVD. Examining the data of patients who have established CVD is important because those patients are at an increased risk of MACE at a much higher rate when compared to those who do not have CVD.

Practice Pearls:

• Adding once-weekly exenatide to the drug regimen of a patient with established CVD and T2D may prove to be beneficial
• The RR of MACE in patients with CVD and T2D was reduced by 10% in the Exenatide cohort
• GLP-1 agonists are beginning to show a clinical trend of decreasing RR of MACE in patients who are at a higher risk for it

Mentz, Robert J., et al. “Effects of Once-Weekly Exenatide on Clinical Outcomes in Patients With Preexisting Cardiovascular Disease.” Circulation, vol. 138, no. 22, 27 June 2018, pp. 2576–2578., doi:10.1161/circulationaha.118.036811.

“Once-Weekly Exenatide Reduces MACE Risk in Patients with Type 2 Diabetes, CVD.” Healio, www.healio.com/cardiology/chd-prevention/news/online/{9af721ba-833a-4e21-ac1e-e45b8cf0bf68}/once-weekly-exenatide-reduces-mace-risk-in-patients-with-type-2-diabetes-cvd.

Usif Darwish, PharmD Candidate, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences