A new study is the first study to find that these drugs lower the risk of colorectal cancer more than other common diabetes drugs.
The new weight loss drugs are called glucagon-like peptide-1 receptor agonists (GLP-1RA). The first drug, exenatide (Byetta), was approved to treat type 2 diabetes (T2D) in 2005. It was a breakthrough for people with T2D, but not a media attention grabber. As researchers continued to develop new GLP-1RA drugs, and as people started using them more, it became apparent that people on the drugs were losing weight.
In 2021, the drugs really caught fire when semaglutide was approved for weight loss with diabetes under the brand name Ozempic and for weight loss without diabetes under the name Wegovy. Studies found that people lost 15 percent of their body weight in about 16 months when using these drugs. Other studies have found that these drugs may also reduce the risk of high blood pressure, kidney disease, stroke, and heart disease.
******
******
A new study from researchers at Case Western Reserve University School of Medicine is the first to add another benefit for the weight loss drugs: a significantly reduced risk of colorectal cancer. The study was published in the prestigious American Medical Association’s journal JAMA Oncology.
The research team used medical records from more than 1 million Americans who were started on a T2D drug between 2005 and 2019. These drugs included new GLP-1RA drugs as well as tried-and-true T2D drugs like insulin and metformin. Over a period of 15 years, patients taking a GLP-1RA drug were 44 percent less likely to be diagnosed with colorectal cancer than those taking insulin and 25 percent less likely than those taking metformin.
GLP-1RA drugs mimic the effects of glucagon-like peptide 1, a hormone (or chemical messenger) that is secreted in the intestines when you eat and your blood sugar starts to go up. The GLP-1 hormone tells the pancreas to release more insulin. Insulin is the hormone that allows the cells of your body to use sugar (glucose) for energy. The extra insulin boost from GLP-1 helps lower blood sugar levels. In addition to the insulin bump, the GLP-1 hormone slows down digestion.
The GLP-1RA drug is different from the GLP-1 hormone because it has molecular changes that increase the amount of time the drug lasts at the messenger receptor sites in the pancreas from minutes to weeks. A drug that mimics the effect of a hormone is called an agonist.
Lowering blood sugar and slowing digestion may both contribute to weight loss, but the GLP-1 drugs have another important effect, not in the pancreas, but in the areas of the brain responsible for feeling full and causing cravings. They cause you to feel full sooner, called satiety, and they decrease cravings for food. New research suggests that this decrease in craving may also be effective for helping people with addictions to drugs, alcohol, or nicotine.
The Case Western Reserve research team wanted to find out if the new weight loss drugs could reduce the risk of an obesity-related cancer like colorectal cancer. There are 13 cancers related to obesity, including breast, uterine, stomach, esophagus, kidney, and liver. In these cancers, obesity increases the risk and makes these cancers more deadly.
The researchers expected to see some reduced risk with weight loss, and they did. What surprised and excited them was that the risk went down even in people who were not obese. This finding strongly suggests that GLP-1RA drugs have another direct or indirect effect on cancer.
The new study was an association study, meaning it looked back at medical records to find the association between GLP-1RA drugs and colorectal cancer. Association is not the same as cause, but it should help guide future clinical trials, called randomized controlled trials, that could confirm the findings. These trials may also include other obesity-related cancers. They may lead to another approval for GLP-1RA drugs, cancer treatment and or prevention.
GLP-1RA drugs have been around long enough and have been used by enough people to have a good understanding of possible side effects. In 2023 alone, close to 2 percent of Americans were prescribed Ozempic or Wegovy. The most common side effects are nausea and vomiting, probably due to slowed movement of food through the digestive system. Other rare complications include a digestive tract obstruction, an increased risk for pancreatitis, and low blood sugar. An increased risk of suicidal thoughts, called suicidal ideation, was suspected, but recent research from Case Western Reserve University School of Medicine in over 3 million patients found suicidal ideation was not increased.
So far, it seems like the effects of GLP-1RA drugs may need to be continued to maintain weight loss. There is evidence that people start to regain weight after stopping the drugs. Time will tell if new versions of these drugs have longer-lasting effects.
Treatment with a GLP-1RA drug can cost more than $1,000 per month. Neither Medicare nor many private insurance companies have started to cover these drugs, especially for weight loss without diabetes. That may be changing soon.
Congress is working on a bill called the Treat and Reduce Obesity Act, which would open coverage for Medicare. The bill is gaining support along with a growing understanding that obesity is a chronic disease, not just a matter of willpower.
Ozempic and Wegovy were approved by the FDA based on a 15 percent loss of body weight. The newest GLP-1RA drug approved for weight loss is tirzepatide (Zepbound), which may reduce body weight by about 25 percent. That is about the same amount of weight loss achieved with weight loss surgery, with fewer complications.
Science magazine named the new weight loss drugs the biggest breakthrough of 2023. NBC News says Zepbound could become the biggest selling drug of all time. Current trials are finding out if these drugs could benefit people with Alzheimer’s or Parkinson’s disease, sleep apnea, drug and alcohol cravings, polycystic ovary disease, and fatty liver disease.
According to the Centers for Disease Control and Prevention, more than 40 percent of Americans are obese, and obesity is a major cause of stroke, heart disease, diabetes, and cancer. Drugs that change our world, like insulin, aspirin, ether, or penicillin, come along rarely. GLP-1RA drugs could be one of those game changers.
