Cardiovascular disease (CVD) is a major cause of sickness and death. Being overweight or obese is a known risk factor for CVD, but it’s been hard to find treatments that produce lasting weight loss and a direct reduction in cardiovascular risk. Instead, medical providers have had success with individual medications that help improve cardiometabolic health by improving CVD risk factors like cholesterol, blood pressure, blood sugar, and inflammation. Now, research shows that we can improve cardiometabolic health with semaglutide, potentially using a single medication instead of many.
Obesity is linked to these issues, which suggests that losing weight might have its own benefits for heart health. A medication called semaglutide—aka Ozempic and Wegovy—has already been shown to decrease major cardiovascular events, like heart attack and stroke, in people with type 2 diabetes. Now, moving beyond individual cardiometabolic risk factors like high cholesterol and blood pressure, scientists are studying the potential of semaglutide to decrease overall cardiovascular risk in people without diabetes who have overweight or obesity and who have established CVD.
This study, called Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT), is a randomized, double-blind trial. It will compare semaglutide to a placebo to see if the drug is better at reducing major cardiovascular problems. If the trial is successful, it could lead to new approaches for reducing the risk of heart disease while addressing obesity.
Semaglutide and Cardiometabolic Health: STEP 1 and STEP 4
While the SELECT trial is still ongoing, a glimpse of the potential promise to improve cardiometabolic health can be seen in a recent composite, exploratory analysis of two clinical trials showing that semaglutide improved cardiometabolic risk factors in people with overweight or obesity and without diabetes.
In two trials, STEP 1 and STEP 4, the effects of once-weekly injected semaglutide as an adjunct to lifestyle intervention were analyzed. The trials aimed to observe semaglutide’s effect on cardiometabolic risk factors such as waist circumference, blood pressure, fasting blood glucose, fasting serum insulin, insulin resistance, and cholesterol, including non-HDL cholesterol, LDL cholesterol, and triglycerides in adults with overweight/obesity and without type 2 diabetes. The results showed that semaglutide significantly improved these cardiometabolic risk factors compared to placebo. Waist circumference decreased by an average of 4 inches, systolic blood pressure decreased by an average of 6 mmHg, fasting blood glucose decreased by an average of 10 mg/dL, LDL-C decreased by an average of 6%, and triglycerides decreased by an average of 18%.
Semaglutide, Weight Loss, and Cardiometabolic Health
Moreover, greater degrees of weight loss, ranging from decreases in 5 to 20% of body weight, were associated with greater improvements in cardiometabolic risk. And, even more interestingly, this reduction of cardiometabolic risk was independent of weight loss alone, meaning that losing the same amount of weight without semaglutide did not improve cardiometabolic risk to the same degree as doing so with semaglutide. Specifically, improvements in systolic blood pressure, cholesterol, and fasting blood glucose were greater with semaglutide than with placebo in participants within the 10% to <15% and ≥15% weight-loss categories. Larger improvements in diastolic blood pressure, triglycerides, waist circumference, fasting serum insulin, and insulin resistance were observed in the overall population, but not within the weight-loss category subgroups, and therefore appeared to be predominantly attributable to the greater degree of weight loss achieved with semaglutide.
Semaglutide, Cardiometabolic Health, and Reduced Medication Burden
Lastly, improvements in cardiometabolic risk factors from semaglutide led to a reduction in blood pressure and cholesterol medications in both trials. Again, greater weight loss led to greater benefit. In this case, the more weight one lost, the less medication was needed to control blood pressure and cholesterol. Moreover, improvements in blood pressure and cholesterol with semaglutide were maintained even in the context of reduced blood pressure and cholesterol medication use. However, the study also observed that discontinuation of semaglutide resulted in the loss of therapeutic benefit. These findings provide further evidence regarding the beneficial effects of semaglutide on cardiometabolic risk factors in adults with overweight/obesity and without type 2 diabetes.
Takeaway
The STEP 1 and 4 trials provide compelling evidence that we can improve cardiometabolic health with semaglutide for adults with overweight or obesity and without T2D. The beneficial effects appear to be largely driven by weight loss, but some effects may be additive to weight loss alone. The results also suggest that semaglutide treatment may reduce the need for blood pressure and cholesterol lowering medications. Future studies, including the ongoing SELECT trial will further explore the potential benefits of semaglutide. Overall, these findings represent an important step forward in the management of obesity-related cardiometabolic risk factors.
