medwireNews: Glucagon-like peptide (GLP)-1 receptor agonists may delay the incidence of major adverse cardiovascular events (MACE) by an average of 0.6 months over a 4-year period in people with type 2 diabetes, meta-analysis data suggest.
The delay was longer among people with existing cardiovascular (CV) disease, and the data “corroborate previous findings that, as a class, these agents have significant cardiovascular benefits,” write Salil Deo (Case Western Reserve University, Cleveland, Ohio, USA) and co-authors in Diabetes, Obesity and Metabolism.
The meta-analysis included data from eight large CV outcomes trials (REWIND, LEADER, SUSTAIN-6, Harmony Outcomes, Amplitude-O, ELIXA, and EXCSEL) comprising a total of 60,080 participants with type 2 diabetes who were randomly assigned to receive a GLP-1 receptor agonist or placebo.
Rather than using hazard ratios, which “are difficult to interpret,” the researchers calculated the difference in restricted mean survival time (ΔRMST) between study arms to evaluate the cardioprotective effect of GLP-1 receptor agonists.
They found that, at 12 months, 3-point MACE, defined as CV mortality, nonfatal myocardial infarction, and nonfatal stroke, was delayed by an average of 0.03 months with GLP-1 receptor agonists versus placebo.
The mean delay increased with time, and at 24, 36, and 48 months was a respective 0.15, 0.36, and 0.62 months.
Deo et al point out that there was an 80% increase in ΔRMST between 36 and 48 months, which they say suggests that “the continued use of GLP1-RA drugs may lead, over time, to larger increases in event-free survival.”
When the investigators excluded the ELIXA trial, which had 4-point MACE as the primary outcome, the mean delay in 3-point MACE at 48 months increased further, to 0.72 months, with GLP-1 receptor agonists versus placebo.
Furthermore, restricting the pooled analysis to the three studies in which the majority (≥85%) of participants had established CV disease also impacted ΔRMST. In this case, 3-point MACE was delayed by an average of 1.10 months with GLP-1 receptor agonists versus placebo at 48 months.
Among the individual outcomes, there was no significant difference between the two groups in the time to CV mortality or myocardial infarction at 48 months, but stroke and all-cause mortality were delayed by a significant 0.22 and 0.26 months, respectively, with GLP-1 receptor agonists versus placebo.
Deo and colleagues say that a recent meta-analysis of the same eight trials reported that GLP-1 receptor agonists conferred a 14% relative risk reduction for 3-part MACE versus placebo. “However, this result has limited interpretation without knowing the absolute risk of MACE in controls and how this varies over time,” they write.
The authors add: “In contrast, an average gain of 0.6 months over 4 years is easy for patients and clinicians to understand and discuss, especially as the absolute benefit appears to increase non-linearly over time.”
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Diabetes Obes Metab 2022; doi:10.1111/dom.14738