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Meta-analysis: GLP-1 receptor agonists reduce CV risks in type 2 diabetes
Adults with type 2 diabetes are effectively treated with GLP-1 receptor agonists compared with placebo and experience significant decreases in cardiovascular mortality, all-cause mortality and the three-point major adverse CV events outcome, study data show.
M. Angelyn Bethel, MD, assistant professor of diabetes and endocrinology and leader of the mega-trials program at the Diabetes Trial Unit at the University of Oxford, and colleagues conducted a systematic review and meta-analysis of four trials assessing the safety and efficacy of GLP-1 receptor agonists on CV outcomes, including but not limited to CV mortality, nonfatal MI and nonfatal stroke, compared with placebo in adults with type 2 diabetes.
The trials included were ELIXA, which evaluated lixisenatide (Lyxumia, Sanofi); LEADER, which evaluated liraglutide (Victoza, Novo Nordisk); SUSTAIN-6, which evaluated semaglutide (Ozempic, Novo Nordisk); and EXSCEL, which evaluated extended-release exenatide (Bydureon, AstraZeneca). ELIXA, LEADER and SUSTAIN-6 all evaluated the outcome for three-point major adverse CV events (CV mortality, nonfatal myocardial infarction and nonfatal stroke).
Participants in all four trials were of similar age (60 to 65 years), 61% to 70% were men and 75% to 83% were white. All participants had mean diabetes duration between 9.3 and 13.9 years and mean baseline HbA1c from 7.7% to 8.7%; follow-up ranged from 2.1 to 3.8 years.
GLP-1 receptor agonists were associated with a 10% RR reduction for the three-point major adverse CV event compared with placebo (HR = 0.9; 95% CI, 0.82-0.99). Further, these agents were associated with a 13% RR reduction for CV mortality (HR = 0.87; 95% CI, 0.79-0.96) and a 12% RR reduction for all-cause mortality (HR = 0.88; 95% CI, 0.81-0.95) compared with placebo. Risks for fatal and nonfatal MI, fatal and nonfatal stroke, hospital admission for unstable angina and hospital admission for heart failure were not significantly associated with GLP-1 receptor agonists compared with placebo.
“The capacity of drugs in the GLP-1 receptor agonist class to reduce major adverse cardiovascular events in patients with type 2 diabetes at moderate to high cardiovascular risk, and to do so without detrimental effects on other safety parameters represents a major therapeutic advance,” the researchers wrote. “Existing data show that the risk-benefit profile for the GLP-1 receptor agonist class seems favorably balanced, but categorization of drugs by class is less useful when making individual patient treatment decisions. Differences between the GLP-1 receptor agonist drugs do exist in their structure, potency and effect on cardiovascular risk. The choice of GLP-1 receptor agonist for an individual patient should be based on available evidence for effects on cardiovascular risk and incorporate drug characteristics important to risk, such as convenience, potency, ease of delivery, tolerability and price.”
In an accompanying editorial, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland School of Medicine, wrote that all four CV outcome trials of GLP-1 receptor agonists “support a one-size-fits-all therapeutic approach.”
“However, there is considerable inter-individual variation with respect to the magnitude of clinical benefit, suggesting that a personalized medicine strategy might enable physicians to select the best drug for each patient. ... Future research will be necessary to clarify how BMI or other clinical criteria should be taken into account when predicting the magnitude of clinical benefit likely to be provided by specific drugs used for the treatment of type 2 diabetes,” he wrote. – by Amber Cox
Disclosures: The study was funded by Amylin Pharmaceuticals (AstraZeneca). Bethel reports she receives research support from AstraZeneca, GlaxoSmithKline and Merck; and participated in advisory boards, steering committees or data safety monitoring boards for AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Theracos; and received honoraria for participation in academic conferences from Sanofi. Taylor reports he receives personal fees from Ionis Pharmaceuticals, grants from Regeneron, owns stock in Abbott Laboratories, Amgen and Celgene; and was previously employed at Bristol-Myers Squibb. Please see the study for all other authors’ relevant financial disclosures.