A diabetes and weight-loss medication is now making headlines for a powerful new role: directly protecting the heart. Recent findings from a major global trial indicate that semaglutide offers significant cardiovascular benefits, emerging rapidly and sustained over time, even in patients who experience minimal weight reduction. This revelation is prompting cardiologists to reconsider strategies for managing heart disease risk in a broad patient population.
The SELECT Trial: A Landmark Study on Heart Health
Researchers initiated the pivotal SELECT trial in 2018. It enrolled 17,604 adults across 41 countries. Participants were aged 45 to 75, all living with overweight or obesity and a confirmed history of cardiovascular disease—such as a prior heart attack or stroke—but without a diabetes diagnosis.
In this double-blind study, half the participants received a weekly injection of 2.4 mg of semaglutide, while the other half received a placebo. All continued their standard care, including medications for cholesterol and blood pressure, alongside lifestyle counseling. The trial's data collection concluded in 2023, with follow-up continuing through June 2024.
The results were striking. Over nearly three years, the group taking semaglutide experienced a 20 percent reduction in major adverse cardiovascular events (MACE). This composite endpoint includes nonfatal heart attacks, nonfatal strokes, and cardiovascular death. Specifically, 6.5 percent of the semaglutide group experienced a MACE event, compared to 8 percent in the placebo group. Deaths specifically from heart causes fell by 15 percent.
Rapid Benefits Independent of Weight Loss Puzzle Experts
One of the most surprising aspects for clinicians was the speed of the benefit. Positive effects on some cardiovascular endpoints were observed as early as eight weeks into the treatment. This timeline preceded both the period of maximum weight loss and the establishment of a steady dosing regimen.
While the average weight loss reached approximately 10 percent by month 20, the heart protection began much sooner. An analysis led by John Deanfield and his team at University College London found that reduction in waist size explained only 30 to 38 percent of the cardiovascular gains at the two-year mark.
Crucially, even participants who lost less than five percent of their body weight enjoyed the full cardiovascular benefit, matching the outcomes of those who shed more. This effect was consistent across a wide range of body sizes, from a Body Mass Index (BMI) of 27 to over 50. Deanfield described this as surprising, suggesting it points to direct cardioprotective mechanisms of the drug beyond weight management.
How Semaglutide Works Its Cardiovascular Magic
Semaglutide functions by mimicking a natural gut hormone called GLP-1, which helps control appetite and stabilize blood sugar levels. For the heart and blood vessels, its benefits are believed to stem from multiple actions:
- Reducing chronic inflammation in artery walls.
- Slowing down the buildup of arterial plaque.
- Improving blood vessel function and health.
- Positively influencing blood pressure and blood lipids, independent of calorie reduction.
Animal studies also suggest it may reduce scarring in heart muscle after a heart attack. In patients with obesity, who often have chronic, low-grade inflammation that worsens heart disease, semaglutide appears to dampen this inflammatory fire early. One analysis showed consistent reductions in C-reactive protein, a key marker of inflammation, starting from week four. Systolic blood pressure also showed a modest average improvement of about 3 mmHg.
Real-World Implications for India's Heart Disease Burden
The findings hold particular significance for India, where heart disease often strikes a decade earlier than in Western populations. This early onset is frequently linked to central obesity (belly fat) and clustering of metabolic conditions. With obesity rates rising rapidly in urban centers like Delhi and Mumbai, semaglutide could become a vital tool in preventive cardiology.
Since the SELECT trial specifically excluded people with diabetes, its results highlight a clear benefit for a broad group of heart patients living with overweight or obesity. While guidelines from the American College of Cardiology already recognize GLP-1 drugs for high-risk patients, Indian doctors are now looking at it for post-heart attack patients with a BMI over 27.
The primary hurdle remains cost, with current monthly expenses around Rs 10,000, though the future arrival of generic versions may improve accessibility. The most common side effects are gastrointestinal, including nausea in about 20 percent of users early on, which typically subsides. The trial noted a slightly higher incidence of gallbladder-related issues, but found no excess risk of pancreatitis or thyroid cancers.
The SELECT trial paves the way for further research, including the SOUL trial which is testing an oral version of the drug in broader groups. Scientists are also exploring combinations with statins or blood thinners. For now, experts urge patients to have detailed discussions with their cardiologist before considering this therapy, especially those with kidney issues or a family history of thyroid cancer.
This breakthrough underscores how modern treatments can have multiple, powerful effects. What began as a diabetes aid evolved into a weight-management tool, and now stands validated as a direct guardian of heart health. It offers patients and doctors a new option to prevent subsequent cardiac scares, complementing essential lifestyle measures like regular walking and a healthy diet. As evidence continues to grow, semaglutide is poised to become a standard fixture in cardiovascular prevention toolkits worldwide.
