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Once-weekly exenatide reduces MACE risk in patients with type 2 diabetes, CVD
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PHILADELPHIA — Among patients with type 2 diabetes and confirmed CVD at baseline, treatment with once-weekly exenatide reduced the risk for major adverse CV events, with no new or overall safety concerns related to cardiac events, according to a prespecified subgroup analysis of the EXSCEL study.
“We were interested in exploring clinical outcomes with exenatide once weekly in the [approximate] 70% of the [EXSCEL] cohort with known CVD at baseline,” Robert J. Mentz, MD, associate professor of medicine, director of the Duke Cooperative Cardiovascular Society and associate program director at the Duke Cardiovascular Disease Fellowship, told Healio. Mentz, a Cardiology Today Next Gen Innovator, presented the subgroup data at the third annual Heart in Diabetes conference.
Mentz and colleagues examined data on 10,782 participants from the EXSCEL study who had type 2 diabetes and confirmed CVD at baseline. At the start of the study, 72% of patients had CAD, 23% had cerebrovascular disease and 25% had peripheral vascular disease. This subgroup comprised 73% of the overall EXSCEL population. The median age was 63 years and 33% were women.
Patients were stratified into groups based on treatment with once-weekly exenatide 2 mg injection (Byetta, AstraZeneca) or placebo. The primary endpoint was major adverse CV events (MACE), including CV death, nonfatal MI and nonfatal stroke. Median follow-up was 3.2 years.
In the overall EXSCEL trial, MACE was lower in the exenatide group compared with placebo (11.4% vs. 12.2%; HR = 0.91; 95% CI, 0.83-1), but this finding was not statistically significant in terms of superiority, with a P value of .061, Mentz told Healio. The rate for all-cause mortality was also lower in the exenatide group (6.9% vs. 7.9%; HR = 0.86; 95% CI, 0.77-0.97), Mentz said.
In the subgroup of patients with known CVD at baseline assigned once-weekly exenatide, the researchers reported a 10% RR reduction for MACE (13.4% vs. 14.6% for placebo; HR = 0.9; 95% CI, 0.816-0.999), with a nominal P value of .047, Mentz told Healio.
When examining secondary endpoints in this CVD subgroup, including all-cause mortality, CV mortality, MI, stroke and hospitalization for ACS or HF, all but hospitalization for ACS (HR = 1.03; 95% CI, 0.911-1.161) favored once-weekly exenatide. However, none of the secondary endpoints met a nominal level of statistical significance, Mentz told Healio.
The subgroup data are important, Mentz said, because “the patient group with known CVD is the group at greater risk for future events and higher event rate,” which may have supported the ability to detect a clinical benefit.
“These findings add to the increasing body of literature supporting that the GLP-1 receptor agonist class of medications demonstrates a fairly consistent benefit in improving MACE, with the greatest benefit seen in those with underlying CVD,” Mentz said.
The data were previously published in Circulation. – by Earl Holland Jr.
References:
Mentz RJ, et al. Once-weekly exenatide in patients with preexisting cardiovascular disease. Presented at: Heart in Diabetes CME Conference; July 12-14, 2019; Philadelphia.
Mentz RJ, et al. Circulation. 2019;doi:10.1161/CIRCULATIONAHA.118036811.
Disclosures: Mentz reports he received research support from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline and the NIH and advisory fees from Boehringer Ingelheim. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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George L. Bakris, MD
The Mentz lecture reviews the EXSCEL study testing the once-weekly GLP-1 agonist exenatide. This was a double-blind, placebo-controlled trial in over 14,700 people with very high CV risk and about 70% having a prior CV event. The primary endpoint was MACE CV death, nonfatal MI and nonfatal stroke and had a median follow-up of 3.2 years. The study met the noninferiority endpoint but not the superiority endpoint. Of note, only 1% of the people in this trial were taking an SGLT2 inhibitor. Moreover, there was no benefit in HF risk; however, those with a previous CV event demonstrated a 10% risk reduction for MACE with exenatide.
The GLP-1 agonists as a class demonstrate benefit on MACE reduction, but only two trials — LEADER and SUSTAIN-6 — are very positive. The others in the class trend toward positive outcomes in high-risk groups; however, the more recent HARMONY and REWIND trials are significant for CV risk reduction, hence, as a class, they are clearly shown to reduce CV risk and events.
This trial further supports the GLP-1 agonists as CV risk-reducing agents and should be preferred in people with high CV risk or those who have already had an event. This trial further supports these agents as safe and with benefits in contrast to most other classes of glucose-lowering drugs except the SGLT2 inhibitors.
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