medwireNews: Semaglutide significantly reduces the risk for nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes relative to placebo in people with cardiovascular disease and overweight or obesity but no history of diabetes, SELECT study findings indicate.
“The magnitude of the effect of semaglutide in the current trial was similar to that among patients with diabetes in previous studies (within the constraints of between-trial comparisons), which suggests that treatment with semaglutide could be applied more broadly for secondary prevention of cardiovascular events in the expanding population of patients with overweight and obesity and atherosclerotic vascular disease,” write A Michael Lincoff (Cleveland Clinic, Ohio, USA) and co-authors in The New England Journal of Medicine.
“Moreover, because two thirds of the patients in this trial had dysglycemia (glycated hemoglobin [HbA1c] levels of 5.7 to 6.4%), our findings support a more attentive therapeutic approach to prediabetes, not only because of the association between prediabetes and cardiovascular risk but also because of the opportunity to improve cardiovascular outcomes through appropriate weight management.”
The SELECT study included 17,604 participants aged 45 years and older (mean age 62 years; 72% men) with cardiovascular disease and a BMI of 27 kg/m2 or greater (mean 33 kg/m2) but no history of diabetes from 804 clinical sites in 41 countries. They had a mean HbA1c of 5.8% (39.9 mmol/mol), and 66.4% met the HbA1c criterion for prediabetes of 5.7–6.4% (38.8–46.4 mmol/mol).
Lincoff et al report that, during a mean 39.8 months of follow-up, 6.5% of the 8803 participants randomly assigned to receive once-weekly subcutaneous semaglutide 2.4 mg experienced the primary cardiovascular endpoint event of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.
The rate was 8.0% among the 8801 participants given placebo, a significant difference that corresponded to a 20% risk reduction in favor of semaglutide.
The researchers note that the “effects of semaglutide occurred early after the initiation of treatment and were directionally similar across cardiovascular end points and among prespecified patient subgroups.”
Lincoff and team also found that semaglutide was associated with greater improvements in multiple biomarkers of cardiovascular risk versus placebo, including blood pressure, body weight, waist circumference, glycemic control, nephropathy, and levels of lipids and C-reactive protein.
They say that the 3.3 mmHg greater decrease in systolic blood pressure with semaglutide over placebo they observed “is greater than the decrease of 2 mm Hg predicted by a meta-analysis to yield a 7% reduction in vascular mortality, and the 37.8-percentage-point [greater] decrease in the high-sensitivity C-reactive protein level with semaglutide in this trial is similar to that reported with statins.”
The authors also point out that the changes in cardiovascular biomarkers they recorded “are notable for having been achieved on a background of high rates of use of statins, antihypertensive agents, and other evidence-based medications for atherosclerotic disease.”
Serious adverse events (AEs) occurred in 33.4% of patients in the semaglutide group and 36.4% of those in the placebo group. Significantly more people given semaglutide than placebo discontinued treatment due to AEs (16.6 vs 8.2%). The most common reasons for discontinuation were gastrointestinal disorders (10.0 vs 2.0%) and gallbladder-related disorders (2.8 vs 2.3%).
Lincoff et al conclude: “Semaglutide improved cardiovascular outcomes in this trial, whereas lifestyle and pharmacologic interventions for overweight or obesity tested in previous trials have uniformly failed to do so.”
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