Almost 50 years ago, medicine experienced the first approvals by regulatory agencies of drugs aimed at combating obesity, known to be responsible for increasing the risks of cardiovascular diseases such as heart attack, stroke and other episodes that can be disabling and lead to death. Until the 2010s, attempts to reduce weight to protect the heart and all its complex web failed in the face of overwhelming side effects. Depression, heart attacks and suicidal ideation have made obese people rely on a combination of exercise and diet, bariatric surgery or medications with subtle impacts to prevent and reduce organ and artery damage. But a game-changer may be looming as new drugs developed for the treatment of diabetes and already used for obesity are showing potential for protecting cardiovascular health, lowering blood pressure and preventing the accumulation of fat in the arteries (atherosclerosis). ). In the last week, the drug semaglutide was at the center of the main panels of the European Society of Cardiology (ESC) congress, held in Barcelona, Spain, as a drug entering the list of specialist indications to attack the problem.
In the last decade, studies have helped to consolidate the idea that cardiovascular events, type 2 diabetes and obesity form a triangle to be tackled together and that treatment strategies should not allow either side to be decompensated. Until then, the challenge seemed difficult to face. Medicines aimed at diabetes were like a pump for the heart and science had to deepen research on new drug options starting in 2008, when the US regulatory agency Food and Drug Administration (FDA) determined that the pharmaceutical industry should implement means to avoid cardiovascular risk in this class of drugs.
With the advancement of work based on these guidelines, there was the advent of substances that act on hormone receptors produced by the intestines, such as LPG-1, important for the regulation of appetite and a reduction in the rate of emptying of the stomach, something that increases the duration of the feeling of satiety. From there, a chain reaction began to surprise researchers.
Semaglutide proved to be effective against diabetes, but patients also started to have a weight loss that reached 17% at a dosage of 2.4 mg applied once a week. And the most recent studies point out that the heart ends up benefiting in this process. “It is a drug for diabetes that has indirect actions in reducing blood pressure, weight, reduces inflammation in the body and has anti-atherosclerosis action”, details Marcelo Assad, president of the atherosclerosis department of the Brazilian Society of Cardiology. The cardiovascular benefits in patients with diabetes were proven in a study with 4,807 people published in 2018. Among the side effects are: nausea, diarrhea and vomiting.
Real-life data from people with type 2 diabetes and atherosclerosis indicate that semaglutide may be the way to significantly reduce stroke risk. Conducted by University Hospital Llandough in the UK and presented at the ESC conference, an analysis of 17,920,000 Americans with type 2 diabetes and 4,234 with type 2 diabetes and atherosclerosis compared those who received the medication and those who received a inhibitor of a protein called dipeptidyl peptidase 4 (DPP-4i), which works to control blood glucose.
In the semagglutin group, 34 participants with type 2 diabetes had a stroke. Among those who received DPP-4i, there were 60. The results were even better in the group with diabetes and atherosclerosis: 13 episodes among those who received semaglutide and 32 in those who took DPP-4i. Currently, semaglutide is authorized for use in patients with diabetes in several countries, such as Brazil, where the permitted dosage is 1 mg. For obesity – with a dosage of 2.4 mg – approval has been given in some places, such as the United States, United Kingdom and Japan.
Although the medication has shown evidence of cardiovascular protection, there are no studies focused on this aspect to prove the finding. The question is whether, in the face of so much evidence that the heart can be shielded by this medication, the same results will be achieved in patients without diabetes and only with obesity, a chronic disease that reaches alarming rates. There is 1 billion obese people in the world and the World Health Organization (WHO) estimates that, in three years, 167 million people will have their health affected by excess pounds.
Even though it is an epidemic, the race to stop this process is filled with obstacles and the main one is the difficulty of getting patients to start and maintain the implementation of healthy habits. Stigma and prejudice are also barriers. “It is a complex disease, with difficult targets. We know that 30% of obese people have been diagnosed and less than 12% are undergoing treatment,” Luc Van Gaal, professor emeritus at the University of Antwerp hospital in Belgium, told an audience of cardiologists.
The expectation is now for the Select study, carried out by the Danish pharmaceutical company Novo Nordisk with the medication and which has the participation of 17,500 obese people over 45 years of age in 41 countries, including Brazil, where 600 volunteers will be evaluated. The results should be presented at the end of next year.
“We’ve seen the potential for reducing cardiovascular disease, but our job is to have data and evidence to confirm and provide input to regulatory agencies and medical societies to develop guidelines,” says Martin Lange, executive vice president of company development. In such a sensitive topic, which involves such serious diseases, scientific rigor is welcome. While this evidence is not enough, healthy eating, physical exercise and the control of chronic diseases continue to be the triad that will never leave medical recommendations.
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