The first study to assess how weight-loss drugs affect the whole of human health has discovered an "eye-opening" impact on the body, researchers say. The analysis, involving about two million people, linked the drugs to better heart health, fewer infections, a lower risk of drug abuse and fewer cases of dementia. The US researchers also warned the drugs were "not without risk" and seemed to increase joint pain and potentially deadly inflammation in the pancreas. However, the results need very careful interpretation. Weight-loss drugs have exploded in popularity - but a full understanding of everything they touch in the body is still coming together. "This is new territory," said lead researcher Dr Ziyad al-Aly, clinical epidemiologist at Washington University. Initially, they were a proven treatment for type 2 diabetes. Then, weight loss was noticed as a significant side-effect - and Ozempic and Wegovy became household names. How do weight loss drugs like Mounjaro and Wegovy work? The study used data on US veterans with type 2 diabetes, some of whom were given Ozempic or Wegovy and some more standard drugs - to measure their effect on 175 other illnesses. There appeared to be a significant boon to heart health, with lower levels of heart attacks, stroke, heart failure and high blood pressure, in those taking the new weight-loss drugs. They also cut the risk of substance abuse (including alcohol, opioids and cannabis) as well as reducing schizophrenia, suicidal thoughts and seizures. Despite the study being short, and people taking the drugs for only 3.5 years because of how new they are, it reported a 12% reduction in Alzheimer's disease. There was also less liver cancer, muscle pain and chronic kidney disease as well as a noted reduction in bacterial infections and fever. On the flip side, people were more likely to have problems in their digestive system. Feeling sick, tummy pain, inflammation in the stomach, diverticulitis (bulges in the intestines that can be painful) and haemorrhoids were more common on Ozempic or Wegovy. The data, published in the journal Nature Medicine, also showed low blood pressure, including fainting, headaches, disturbed sleep, kidney stones, inflammation in the kidneys and a range of bone or joint pains, including arthritis, became more frequent. "It was definitely eye-opening for me to see all these different hits in different organ systems," Dr Aly told BBC News. The explanations for the drugs' seemingly wide-ranging impact are both obvious and mysterious. Losing excess weight would in turn improve health. For example, lower levels of sleep apnoea – when breathing stops and starts while slumbering – is thought to be down to losing weight around the tongue and throat, which can block the airways. But the drugs also appear to be directly altering the behavior of cells and tissues in the body. Dr Aly said: "Obesity is bad for the brain. Obesity is bad for mental health. Obesity is bad for the heart. Obesity could be the mother of all ills." Ozempic and Wegovy have the same active ingredient, semaglutide, in different doses, and mimic the hormone glucagon-like peptide-1. Released by the gut after eating, GLP-1 travels through the blood and sticks to little receptors on the surface of brain cells. This tells the brain there is food in the stomach and is why people feel less hungry after eating. However, receptors that respond to GLP-1 are found throughout the body, including in the heart and some parts of the immune system. "It is very clear this class of drugs seem to suppress reward mechanisms [in the brain so it] inhibits that urge to seek out alcohol, to seek out tobacco, to seek out gambling," Dr Aly said. Meanwhile, lower levels of inflammation, the alarm bell of the immune system, could have a wide range of health impacts. The range of health benefits may strengthen the case for some people using the drugs, Dr Aly said. "When you add more benefit, for the people who really are at risk of these conditions, that's an added plus," he said. But for those whose weight is not affecting their health, "maybe the risk that they're buying themselves is actually much higher than the benefit". However, the study has drawbacks that limit its findings. Most of the veterans were white men, so it did not include any female-specific effects, such as the anecdotal phenomenon of improved fertility and unexpected "Ozempic babies". And there could be reasons why some had been prescribed Ozempic or Weygovy, rather than other drugs, that could provide alternative explanations for some of the findings. Thorough clinical trials have already proven benefits to heart health - and nausea is a known side-effect - but other findings will need to go through similar rigorous testing. Alzheimer's starts more than a decade before symptoms appear - but this study suggests just a few years on semaglutide has a protective effect. Trials are already under way to work out if this effect is real. "Such trials will lead us much closer to the truth," Prof Naveed Sattar, from the University of Glasgow, said. "Fortunately... several will report out in the next one to four years." And while "interesting", he said this latest study's findings were not strong enough to influence how the drugs were prescribed. Prof Sir Stephen O'Rahilly, from the University of Cambridge, said the study needed to be interpreted "carefully" but provided "useful reassurance" about the drugs' safety in people with diabetes. And further studies in other patients were "awaited with interest". The "most surprising finding" was the increase in joint pain, since weight loss should reduce pressure on the joints. But the fact some cells in the immune system had GLP-1 receptors meant the impact of these drugs was "somewhat unpredictable" and while some inflammatory disorders may be eased, "others might conceivably be exacerbated", Prof O'Rahilly said. — BBC
