Scientific research

All medications have side effects, just take a look at any leaflet to see this. But there are not many cases in which these amount to the main effect. This is what happened a few years ago with GLP-1 agonists, medications used for decades to treat type 2 diabetes that began to demonstrate weight-loss effects. After several reformulations, new commercial brands, such as Ozempic and Wegovy, became an effective way to end obesity. But science is proving that there are many other side effects that could become major ones. GLP-1 is a molecular Swiss army knife, a kind of all-purpose drug. They affect our bodies in ways we still don’t fully understand. But today we are closer to listing. A team of scientists from the University of Washington School of Medicine has published the first detailed atlas of the side effects of these drugs. They have found benefits for cognitive and behavioral health, while revealing an increased risk of developing pancreatitis and kidney conditions. “Until now we had seen anecdotes and reports here and there. “Some people saying that it can affect this or that,” explained its main author, the clinical epidemiologist, in the presentation of the study. Ziyad Al-Aly, from the John J. Cochran Veterans Hospital. “But no one, no one had thoroughly investigated the effectiveness and risks of GLP-1 and all the ways it can affect health.” The study was published this Monday in the journal Nature Medicineshowcase of the best world science. More information “We did an analysis that comprehensively mapped the associations between GLP-1 and 175 potential health effects,” Al-Aly notes. The benefits, beyond weight loss, included a lower risk of substance use disorders and a reduction in suicidal ideation, schizophrenia, and other psychotic disorders. They also observed a reduction in cognitive disorders, such as Alzheimer’s and dementia. And finally, a reduction in the risk of clotting disorders, including stroke. “We found that these drugs have a wide range of beneficial effects, but all this does not come without risks,” warns the expert. The study confirms that, in some cases, they can cause gastrointestinal problems, such as nausea and vomiting. This is quite common and has already been documented in some patients. An increased risk of gastroparesis or stomach paralysis in rare cases and an increased risk of low blood pressure have also been seen. The analysis also notes that the drug may increase the risk of sleep problems and headaches, kidney stones, and drug-induced kidney inflammation. For these reasons, the authors recommend that, when evaluating this treatment, it should always be done under medical supervision and after an individualized analysis. “It is an observational study, although it has a large database and has been carried out for a long time,” he explains. Christopher Moralesan endocrinologist at the Virgen Macarena University Hospital in Seville, who was not involved in the study. The study does not demonstrate, therefore, that the medication is the cause of the listed effects. But these are consistent enough (risk reduction between 10 and 20%) and the database large enough (almost two million patients over three years) to think there is a direct relationship. “With Big Data you can scrape these results in very large databases and this is positive. But we must remember that here we can only verify association, not causality.” The objective of this research, in the words of its own authors, was not to analyze a specific effect and demonstrate causality, but to build an atlas of the association of risks and benefits of this relatively new medicine. “It’s like when Christopher Columbus arrived in America, and he thought about mapping it to get his bearings,” explains Al-Aly. “This is what we are doing, drawing a landscape of benefits and risks.” This opens the door to the possibility that in the future, after many reformulations and research, we can talk about an Ozempic for dementia, alcoholism or Alzheimer’s. There is still a long way to go, but this study has drawn a first map to locate the path. And there are many companies willing to embark on this adventure. There is currently a scientific and commercial race to find the next revolutionary use of GLP-1 agonists. Everyone has in mind the case of Novo Nordisk, the Danish laboratory that presented Ozempic in 2018, and which today has a stock market capitalization of 382,000 million dollars, which makes it the largest company in Europe. This has enormous business and economic implications, but from the scientific world, the question is different. How does an anti-diabetes drug have so many and varied effects? “Medicines don’t work surgically. They are designed to do one thing, but the reality is that this is almost never the case,” reflects Al-Aly. “Biology is complex and multiple, and if you touch one thing you will create a network of various effects.” GLP-1 acts on the intestine, but also on the brain, affecting areas that are involved in impulse control and reward signaling. This would explain why they help mitigate addiction problems. These medications would also affect the blood vessels, and in doing so have a potential effect on the heart. There is research that suggests that they also reduce inflammation, including that of the brain, which could explain their protective effect against neurodegenerative diseases. “But there is also another simpler theory that can explain all these positive health effects,” explains Al-Aly. Obesity is considered a disease in itself, but also the gateway to many others. It is the fifth risk factor for death in the world and every year 2.8 million adults die as a result of this condition. “When we treat obesity, it is normal that this affects other diseases, since it is the mother of them all,” summarizes Al-Aly. The expert has not yet decided, with the available scientific evidence, on which of these two theories has more force. The first would mean that we are talking about a miracle drug with multiple uses. The second would be less profitable for companies, would fill … Read more