Semaglutide, a medication initially developed for type 2 diabetes, is showing promise in rapidly reducing the risk of heart attacks and other serious cardiovascular complications in adults with overweight or obesity who have pre-existing cardiovascular disease but not diabetes. This is according to a secondary analysis of the Semaglutide and Cardiovascular Outcomes (SELECT) trial, presented at the European Congress on Obesity (ECO) in Malaga, Spain.

Early Benefits Observed

The analysis focused on the early impact of semaglutide on cardiovascular events, examining data from randomization up to 12 months, with a specific focus on the 3- and 6-month marks. Researchers aimed to understand the drug’s effects, the timeline for cardiovascular benefits, and identify potential predictors for early cardiovascular events.

These results highlight semaglutide’s early action on decreasing major cardiovascular events, with notable benefits already evident by the first 6 months, and for some, even earlier, even before any major weight loss and before most patients would have been titrated to their full target dose of 2.4 mg.

Dr. Jorge Plutzky, Director of Preventive Cardiology, Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, MA

SELECT Trial Background

The SELECT trial, a landmark study from 2023, demonstrated that adults with overweight or obesity but without diabetes, who had a history of heart attack, stroke, or peripheral artery disease, experienced a 20% reduction in major adverse cardiac events (MACE) when taking semaglutide compared to a placebo over three years. It is important to note that SELECT was not designed as a weight loss trial; participants received semaglutide or a placebo without specific dietary or weight loss guidance.

Study Details and Key Findings

The study involved 17,604 adults (72% male, aged 45 or older) from 804 sites across 41 countries. All participants had overweight or obesity, defined as a body mass index (BMI) of 27 kg/m² or higher. Participants received weekly injections of either semaglutide (titrated to 2.4 mg by week 16) or a placebo.

• 3-Month Results: Semaglutide was associated with a 38% reduction in the risk of major adverse cardiovascular events (MACE) compared to the placebo group (36 vs. 58 events, respectively).
• 6-Month Results: The risk of MACE was reduced by 41% in the semaglutide group compared to the placebo group (67 vs.113 events, respectively).
• Early Stage Impact: Notably, at both 3 and 6 months, most patients had not experienced significant weight loss and were not yet at the full target dose of 2.4 mg of semaglutide weekly.

Mechanisms and future Research

Our findings reveal an early separation in the treatment effect of semaglutide that occurs even without a significant amount of weight lost and prior to full semaglutide titration, said Dr. Plutzky.He added, More research is needed to understand the mechanisms through which semaglutide produces these early clinical benefits, but they may include the drug’s positive effects on reducing inflammation, blood sugar, blood pressure, direct effects on the heart and blood vessels, early dietary changes, or an interaction among these or other responses.

Important Considerations

The researchers emphasized that the SELECT trial focused on individuals with a history of heart disease, placing them at high risk for cardiovascular events. these patients were already taking other cardio-protective medications to manage cholesterol and blood pressure. The benefits of semaglutide were observed along with these existing treatments.