Meta-analysis demonstrates cardioprotective effect of GLP-1 receptor agonists
medwireNews: Treatment with glucagon-like peptide (GLP)-1 receptor agonists reduces the risk for major adverse cardiovascular events (MACE) among people with type 2 diabetes, indicate findings from a large meta-analysis.
“[T]he drugs in this class differ in their structure and duration of action and have been studied in trials of varying sizes and with different patient populations, and in individual trials the effects of these drugs on cardiovascular outcomes have not been consistent,” explain John McMurray, from the University of Glasgow in the UK, and co-authors.
The team analyzed data from seven randomized controlled trials – ELIXA, LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, REWIND, and PIONEER 6 – involving a total of 56,004 patients with type 2 diabetes. The average age of participants at baseline ranged from 60 years in ELIXA to 66 years in PIONEER and REWIND, while the proportion of individuals with established cardiovascular disease ranged from 100% in ELIXA and Harmony Outcomes to 31% in REWIND.
As reported in The Lancet Diabetes & Endocrinology, individuals treated with a GLP-1 receptor agonist had a significant 12% lower risk for MACE (cardiovascular death, stroke, or myocardial infarction) compared with those given placebo, with a number needed to treat (NNT) to prevent one MACE of 75 over a median follow-up of 3.2 years. Analysis of the individual components of the MACE outcome yielded similar results.
Moreover, treatment with a GLP-1 receptor agonist versus placebo was associated with a significant 12% reduction in all-cause mortality risk, a significant 9% reduction in rates of hospitalization for heart failure, and a significant 17% reduced risk for the broad composite renal outcome of macroalbuminuria development, worsening kidney function, end-stage kidney disease, and kidney-related death.
These results indicate that “GLP-1 receptor agonists are clearly cardioprotective drugs,” say the study authors, who point out that the agents were not associated with an increased risk for severe hypoglycemia, pancreatitis, or pancreatic cancer.
The researchers did not identify significant heterogeneity for the protective effect of GLP-1 receptor agonists on MACE risk in people with versus without established cardiovascular disease, suggesting beneficial effects for both primary and secondary prevention. However, they caution that “the number of MACE outcome events in the primary prevention patients was small,” and the data “might not be sufficiently robust to challenge the guideline recommendations only to use GLP-1 receptor agonists to reduce the risk of cardiovascular events in patients with established cardiovascular disease.”
Discussing the findings in an accompanying commentary, Eberhard Standl (Munich Diabetes Research Group eV at Helmholtz Center, Neuherberg, Germany) says that the meta-analysis provides “a timely update after the recent reporting of the primary results from the REWIND trial of dulaglutide and the PIONEER 6 trial of oral semaglutide,” but “many questions remain to be answered, especially regarding benefit in primary prevention patients.”
Although he cautions that “comparisons with other drugs or studies inevitably have inherent limitations due to potential differences in study populations and other specific circumstances,” the commentator says “it is notable that a similar—modest—cardiovascular benefit has been reported for SGLT2 inhibitors.”
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