The SELECT clinical study is a pioneering study that is the first to provide evidence that treating obesity and overweight with semaglutide will improve cardiovascular outcomes for a patient without Type 2 Diabetes.
In total, 17,604 persons with cardiovascular disease and a BMI over 27 were randomly assigned to either semaglutide 2.4 mg weekly injections or a placebo. Researchers followed them for an average of 40 months, examining the rates of strokes, heart attacks, and cardiovascular deaths. SELECT was not a weight loss study. It was a study of cardiovascular outcomes. Thus, the participants in this study received lifestyle recommendations focused on cardiovascular risk reduction, not just weight. Average weight loss in the study was nine percent with semaglutide and one percent for the placebo group after two years. The net result of treatment was a 20% reduction in strokes, heart attacks, and deaths. This is a clear indication of effectiveness for improving cardiovascular health by treating obesity.
The SELECT study makes the medical benefits of obesity treatment undeniable. It will thus have profound implications for health and medicine globally. SELECT shows that treating Obesity is not just aesthetic. We now know that by treating obesity, Health Care Professionals will enable patients to live longer and healthier lives.
Title: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.
Background: study seeks to uncover whether semaglutide reduces cardiovascular risk for patients with obesity and overweight but without diabetes.
Methods: A multicentre, double blind, randomised, placebo controlled, event driven superiority trial. Patients enrolled were over 45, had existing cardiovascular disease (defined as myocardial infarction, stroke or symptomatic arterial disease) and a BMI over 27, with no history of diabetes. Patients were randomly assigned to receive once weekly semaglutide at 2.4mg dose or placebo. The primary endpoint was a composite of death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke in a time to first event analysis. The trial took place at 804 clinical sites in 41 countries.
Statistical analysis: The event driven trial was designed to provide 90% power to detect a relative risk reduction of 17% for a primary end point event in the semaglutide group as compared to the placebo group at an overall one sided significance level of 0.025. Therefore this required that a minimum of 1225 primary end point events be accrued. The clinical study was to be stopped once the 1225 events had accrued.
Results: 17604 patients were enrolled, 8803 were assigned to semaglutide and 8801 to placebo. 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group discontinued the trial due to adverse events (mostly gastrointestinal disorders). The mean age of patients was 61.6 years old and 72.3% were male. 28.5% of patients were in the BMI range classified as overweight (BMI 27-30) while the remainder were classified as obese.
Discussion: Weight loss across a spectrum of elevated BMIs produces not only improvements in glucose levels but also reductions in ectopic adipose tissue deposits that may contribute to atherosclerosis and myocardial dysfunction. Reductions in excess abnormal body fat improve the systemic proinflammatory and prothrombotic environment associated with obesity.
Future areas of study: An important limitation of the SELECT trial is that only patients with pre-existing cardiovascular disease were included. The effects of semaglutide on primary prevention of cardiovascular events in people with overweight or obesity by without previous cardiovascular events were not studied. This is an area for further research. In addition the majority of patients included in this study were white men, more diversity needs to be included in future studies.
To view the abstract please click on this link:
https://www.nejm.org/doi/10.1056/NEJMoa2307563
This is the first clinical evidence to prove that by treating overweight and obesity (BMI 27+) with a pharmacologic, improvements in health can be made. In this case patients had an existing increased cardiovascular disease risk. The question will now be asked how patients without existing disease could improve their health, or reduce their risk of future disease by reducing their weight with a medical weight management program.