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Heart and kidney diseases, cancer: What else can GLP-1 drugs treat in addition to obesity?
Research into the sugar-lowering powers of incretin hormones led to the discovery of GLP-1 drugs [like Ozempic and Mounjaro]. The added bonus of weight loss was serendipity. There seem to be many happy side effects of GLP-1 drugs. Of course, many of them are not because of the drugs themselves but because of weight loss. When you lose weight – whether through diet and exercise, bariatric surgery, or GLP-1 drugs – your knee pain and inflammation will reduce, heart health will improve, and so on. Yet it seems that GLP-1 drugs are directly improving health outcomes as well, apart from the benefits that accrue by reducing blood sugar and hunger. Dr Daniel Drucker, one of the scientists who discovered the GLP1 hormone, conducted an experiment on mice with systemic inflammation. When treated with GLP-1 drugs, the inflammation decreased. However, if the drug was blocked from reaching the brain, the inflammation did not reduce. This suggests that the brain plays a critical role in inflammation, and that reducing it may be directly mediated through the brain and not just indirectly due to weight loss. GLP-1 receptors – the switches activated by the drug – are found in the heart, liver, kidneys, pancreas, stomach, intestines and brain. As with many hormones, GLP-1's effects may not be limited to hunger and satiety alone but may also have multiple other functions. The full range of benefits these drugs can have in treating various diseases is still being discovered. In October 2018, Novo Nordisk, the company that holds the patent for semaglutide, began a trial to study the impact of the drug on the cardiovascular health of people who had heart disease and were overweight or obese but did not have diabetes. They enrolled over 17,000 people from diverse backgrounds. Their mean BMI was 33, and nobody was less than BMI 27. They were divided into two similar groups. One was given semaglutide (Wegovy) and the other was given a placebo. As the trial progressed, Covid-19 struck. Both groups saw similar rates of infection. Among the 184 who died of Covid-19, 78 had been taking semaglutide and 106 were on placebo. The difference is significant enough to suggest that the drug helped save some lives. In the trial, some died of reasons other than the pandemic. After accounting for all causes of death, those taking the drug saw 19 per cent fewer fatalities. No, this does not mean that GLP-1 drugs can be a treatment for Covid-19. What it does show is that the drug is improving overall health through weight loss and reduced inflammation. It confirms what we know about obesity: It's a disease. Did some of those patients survive the pandemic only because weight loss improved their overall health, or also because the drug reduced their inflammation levels, or were there more reasons? This is an open question because scientists are still discovering the full range of what GLP-1 drugs do inside the body. Their action on various diseases could help understand the disease better, perhaps aiding the discovery of new specific drugs and treatments for those diseases. GLP-1 drugs themselves could, some day, be prescribed for many of those conditions. It is important to note that research is ongoing and incomplete. Patients should not self-medicate. Even if GLP-1 drugs are approved by the US FDA or other regulators for some of these conditions, they must be used only under medical supervision. Here are some medical conditions in which GLP-1 drugs have been found to be helpful so far. Heart disease In March 2024, the US FDA approved Wegovy (semaglutide, same as Ozempic) for patients who had heart disease along with obesity or were overweight even if they did not have diabetes. This followed a large trial called SELECT (the same trial that showed the Covid-19 effect fortuitously), which had 17,600 patients enrolled in two groups. In the placebo group, 8 per cent of participants saw major adverse cardiovascular events (MACEs), such as heart attack, stroke or cardiovascular death. In the group taking semaglutide, the incidence was 6.5 per cent. That's a nearly 20 per cent reduction in risk. While this trial used weekly injectable semaglutide, the more recent SOUL trial, involving almost 10,000 participants, used oral semaglutide (Rybelsus) and showed a reduction in MACE of 14 per cent. Statins remain the main drug for people with heart disease, but these results demonstrate the role of semaglutide in the prevention of heart disease on top of statin therapy. Tirzepatide (GIP + GLP-1) has also been shown to reduce cardiovascular risk. In an international trial of 713 adults in nine countries, including the US, called the SUMMIT trial, participants with heart failure taking tirzepatide for two years had significantly improved cardiovascular health and reduced progression of heart failure. An analysis of 13 GLP-1 drug trials comprising more than 80,000 patients showed significant reductions in MACE, overall and cardiovascular mortality, stroke, and need for coronary procedures like angioplasty and surgery, regardless of the presence of diabetes. The benefits could not be explained by weight loss alone. These trials have led to guidelines that all people with diabetes and/or obesity who either suffer from or are at risk of heart disease should be treated with GLP-1 drugs. However, since people with diabetes and/or obesity are at higher risk of heart attack and stroke anyway, it is prudent to consider the prescription of these drugs in most people with diabetes even if they have no evidence of heart disease. Chronic kidney disease In January 2025, the US FDA approved the use of semaglutide in patients who have both diabetes and kidney disease. Our kidneys filter out toxins from the body and pass them through the urine. Their ability to do so starts declining in patients with diabetes. The FLOW trial showed that for patients with both type 2 diabetes and chronic kidney disease, taking semaglutide lowered the risk of complications (dialysis, need for transplant) by 24 per cent. It also slowed down the decline of their kidney function. Moreover, in a post hoc analysis of the SURPASS-4 randomised clinical trial, tirzepatide decreased protein excretion, slowed decline in kidney function and reduced death due to kidney causes in patients with type 2 diabetes. Cancer Since obesity raises the risk of some types of cancer, it is not surprising that studies have started finding a reduced incidence of cancer among those taking GLP-1 drugs. This is similar to the reduced risk of cancer seen among those who have undergone bariatric surgery. Obesity-related cancers are concentrated around the metabolic organs and, among women, around the reproductive organs as well. An observational study of 1.65 million patients in the US found a reduced risk of ten types of obesity-related cancers among diabetes patients taking GLP-1 drugs as compared to those on insulin. Another study found the risk of 13 types of cancer reduced by 22 per cent in those who underwent bariatric surgery and by 39 per cent among those who took GLP-1 drugs. Excerpted with permission from The Weight Loss Revolution, Ambrish Mithal and Shivam Vij, Juggernaut.