Semaglutide Reduces Heart Attack Risk Independent of Weight Loss, Study Finds

Taking semaglutide can lower the risk of heart attacks and other major adverse cardiovascular events, regardless of how much weight is lost or whether patients have diabetes, according to a study published in The Lancet. Researchers from University College London found that semaglutide drugs such as Ozempic, Wegovy, and Rybelsus can reduce the risk of MACE (Major Adverse Cardiovascular Events, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) by four percent for every 5kg less body weight or 5cm smaller waist.

The study, funded by Novo Nordisk, analyzed 17,604 people from 41 countries aged 45 years and over, who were overweight and had cardiovascular disease but did not have diabetes. The scientists involved stated this finding "suggests there are multiple ways the drug benefits the heart, rather than its protective effect on cardiovascular health being due solely to weight loss."

The protective mechanisms may include supporting the health of the lining of blood vessels, reducing inflammation throughout the body, improving blood pressure control, and lowering unhealthy lipid levels. The lead author, a professor of cardiology at the UCL Institute of Cardiovascular Science, noted that abdominal fat is more dangerous for cardiovascular health than overall weight, and therefore it is not surprising to see a link between reduction in waist size and cardiovascular benefit. However, this still leaves two-thirds of the heart benefits of semaglutide unexplained.

"These findings reframe what we think this medication is doing. It is labelled as a weight-loss jab but its benefits for the heart are not directly related to the amount of weight lost. In fact, it is a drug that directly affects heart disease and other diseases of ageing," the professor stated.

Semaglutide is an anti-diabetic and anti-obesity medication belonging to the class of drugs called GLP-1 Receptor Agonists. GLP-1 (Glucagon-Like Peptide-1) is a hormone released from the intestine after eating that helps regulate blood sugar, appetite, and metabolism. Semaglutide mimics the natural GLP-1 hormone in the body by increasing insulin secretion from the pancreas to lower blood sugar, suppressing glucagon to reduce glucose production, slowing gastric emptying to reduce hunger, and acting on brain appetite centers to cause weight loss.

The medication has therapeutic uses beyond weight management. In adults with diabetes and heart disease, it reduces heart attack risk, reduces stroke risk, and lowers cardiovascular mortality. In Type-2 diabetes with kidney involvement, it slows kidney failure progression and reduces death risk. For obesity treatment, semaglutide suppresses appetite, reduces calorie intake, and produces 10-20% weight loss in clinical trials.

Hyderabad-based Natco Pharma recently received approval from the Central Drugs Standard Control Organization (CDSCO) to manufacture and market a generic semaglutide injection in India. Earlier, the drug was extremely expensive and accessible only to a limited population. Generic availability may significantly transform diabetes and obesity management in India, which is often called the diabetes capital of the world.

GLP-1 drugs have ushered in a new era in weight loss. In just a few years, medications such as semaglutide and tirzepatide, known by the brand names Ozempic, Wegovy, Mounjaro and Zepbound, have gone from niche diabetes treatments to household names. A November 2025 poll found that one in eight US adults have tried a GLP-1 medication for weight loss, diabetes or another condition. These drugs' ability to help patients lose anywhere from 15 percent to 20 percent of body weight has made them one of the most powerful nonsurgical obesity treatments ever seen.

However, maintaining weight loss presents significant challenges. A pivotal 2021 clinical study of more than 1,900 adults, known as the STEP 1 trial, laid the groundwork for the use of these drugs as a treatment for weight loss. But a follow-up 2021 study, known as STEP 4, showed that within 48 weeks of no longer taking semaglutide, participants regained approximately two-thirds of their prior weight loss, while those who remained on GLP-1 drug therapy continued to lose weight.

When people lose weight, the body's natural inclination is to return to its previous weight through a phenomenon called metabolic adaptation. As a result, the brain releases more of the hunger hormone ghrelin and dials down leptin, one of the hormones that signals fullness and energy sufficiency. The body interprets weight loss as a threat to survival and responds by slamming the brakes on metabolism through sophisticated energy-conserving mechanisms.

For most patients, the most effective long-term strategy after achieving a target weight is to continue GLP-1 treatment, with clinicians aiming for the lowest dose that still helps regulate appetite and stabilize weight. Another option patients may pursue is to slowly taper off the drugs over about three to six months and to focus on reinforcing lifestyle choices that support goals for overall health and weight maintenance.

Plateaus in weight loss are normal, even on GLP-1 drug therapy. In clinical trials, weight loss with GLP-1 medications tends to follow a predictable curve: rapid early losses during drug initiation and dose increases, a gradual slowing and eventual plateau. A plateau, typically defined as little or no weight change for eight to 12 weeks, is not a sign of failure but rather the body adapting to a lower weight.

Common side effects of semaglutide include nausea, vomiting, constipation, and abdominal pain. Serious but rare side effects include pancreatitis, gallbladder disease, and possible thyroid tumor risk based on animal studies. The medication is not a substitute for lifestyle modification, and long-term safety data is still evolving.

According to the World Health Organisation, obesity has been linked to 3.7 million deaths globally in 2024. If strong action is not taken, the number of people living with obesity is expected to double by 2030. Recently, the WHO released its first-ever guideline on the use of Glucagon-Like Peptide-1, or GLP-1, therapies for managing obesity as a chronic and relapsing condition.