Semaglutide, tirzepatide and other anti-obesity drugs: the benefits and risks identified in the first large study to date

According to one of the most complete studies ever conducted in this area, which is rather recent, weight loss drugs such as the famous Ozempic (actually created for use in forms of type 2 diabetes mellitus) could reduce the risk of developing 42 health conditionsbut at the same time increase the probability of incur another 19.

GLP-1 hormone receptor agonists such as semaglutide have gained resounding popularity in the last decade as treatments for type 2 diabetes and, more recently also thanks to the involuntary endorsement of several celebrities, for obesity. Ozempic and Wegovy, the weight-loss version of the drug produced by Danish Novo Nordisk, have now become household brands. As well as those of Eli Lilly, Mounjaro and Zepbound, based on tirzepatide, and the better known Saxenda, also produced by Novo Nordisk based on liraglutide.

These drugs basically work stimulating the release of insulin and lowering blood sugar levels, an essential application in the case of diabetes. However, they are also known for their slimming effect, probably related to slowing of digestion, to the reduction of appetite and the consequent onset of satiety which leads to eating less. In 2024, Wegovy also received approval in the United States for the treatment of heart diseasealthough the precise mechanism by which it works is not yet entirely clear. However, that case is part of a series of apparently beneficial evidence related to semaglutide by some recent studies.

There is also growing evidence that GLP-1RAs such as exenatide, liraglutide, semaglutide and tirzepatidecan prevent the onset of pathologies such as Alzheimer’s, trigger positive effects on the kidneys and help manage disorders such as addictions. As mentioned, there are also concerns about potential side effects, including gastrointestinal problems.

In a massive new study published in Nature Medicine – the first to analyze in detail the prolonged use of these drugs – researchers have created what they call the clearest picture ever obtained on the efficacy and risks associated with GLP-1 hormone receptor agonists . The analysis involved 215 thousand people with type 2 diabetes, monitored for approximately four yearscomparing the results with a control group made up of over one million individuals treated with anti-diabetic drugs based on other active ingredients. The data was drawn from the US Department of Veterans Affairs database.

The possible benefits

The results showed that these drugs offer numerous benefits, some of which, as mentioned, are already known or have emerged in recent years. For example, those taking these drugs would have a 9% reduced risk of having a heart attack8% to develop deep vein thrombosis, of 12% of incurring theAlzheimer’s compared to the control group. They were also found to be less likely to develop substance use disorders, such as alcohol (11% less) and cannabis (11% less), as well as a 12% reduced risk of bacterial infectionswhich experts can’t really explain. Among other effects, there is also an 18% reduction in the risk of developing psychotic disorders such as schizophrenia.

According to the authors, these findings could help doctors to balance risks and benefits in prescribing drugs based on who they are dealing with. These positive effects could, and it would not be a surprise, derive both from the physical benefits of weight loss and from other actions of GLP-1RAs on the body, such as reduction of inflammation el’influences reward mechanisms in the brain. This was explained by Ziyad Al-Aly, co-author of the study and associate professor of medicine at Washington University, during a press conference last January 16th in view of the publication in the scientific journal the following January 20th.

Possible risks

However, these drugs also carry with them a series of risks. For example, the chances of s increasedevelop gastrointestinal problemssuch as abdominal pain (12% more), hypotension (6% more) and arthritis (11% more). Just like pancreatic problems and an increase in the occurrence of kidney stones, diverticulitis and hemorrhoids.

Since the study is observational, and also based primarily on information from older white males with type 2 diabetes mellitus, cannot demonstrate a causal relationship between GLP-1RA and the effects found, whether positive or negative. To confirm these results, randomized controlled studies would be needed which would also involve obese or overweight people without diabetes and in which the effects of semaglutide and company would be rigorously compared with a control group. In reality, these investigations are already underway and will clarify our ideas in the coming months and years.

Penny Wardprofessor of pharmaceutical medicine at King’s College London, who was not involved in the study, called a Livescience The research is an excellent example of the importance of large medical record databases for evaluating both the safety and possible new applications of increasingly popular therapies for diabetes and obesity.