Could Blockbuster Weight Loss Drugs Also Be Used to Treat Heart Disease, Alzheimer’s, and Cancer?
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It’s hard to imagine GLP-1 agonists making more of an impact — the drugs have already transformed the way type 2 diabetes and obesity are treated. But many experts believe that the drugs hold even more promise in areas that go well beyond blood sugar control and weight management.
Over 1,000 clinical trials involving GLP-1s are currently being conducted all around the world — not just in treating diabetes and obesity, but for conditions such heart disease, stroke, Alzheimer’s disease, polycystic ovary syndrome (PCOS), and even cancer.
Many Health Problems Spring From Inflammation and How the Body Processes Insulin
Although it isn’t unusual for a drug to treat more than one disease state, the wide range of conditions that are being investigated with GLP-1 is. What is it that makes the drug so promising in multiple systems throughout the body?
“I believe that these medications have such broad effects because a lot of health problems begin with disruptions in insulin resistance, abnormalities in how the body handles glucose, and inflammation, which can all be driven by our environments and excess weight gain,” says Jamy Ard, MD, a professor of epidemiology and prevention at Wake Forest University School of Medicine in Winston Salem, North Carolina, and a clinical researcher focused on studying strategies to treat obesity and Type 2 diabetes in adults.
GLP1-based drugs are very effective at helping people reduce the number of calories they consume, and therefore have direct effects on insulin sensitivity and glucose metabolism, says Dr. Ard. They also reduce inflammation, but it’s still unclear if that’s a direct effect of GLP-1 drugs or it’s simply a result of the weight loss, he says.
“When you combine these, it creates an overwhelming biological effect. There is no organ system that is not affected by this internal metabolic environment,” says Ard.
GLP-1 Receptors Exist Throughout the Body
Although GLP-1s work in the pancreas to regulate insulin and glucagon secretion, GLP-1 receptors are widely distributed in other areas of the body, including the brain, cardiovascular and immune systems, gut, and kidneys, says Diana Isaacs, PharmD, an endocrine clinical pharmacy specialist at the Endocrine and Metabolism Institute at Cleveland Clinic in Ohio.
“These receptors in other areas of the body make it promising to treat other conditions,” says Dr. Isaacs. “This drug class has already shown incredible value for type 2 diabetes and obesity, and it’s exciting to think about the potential to treat even more conditions.”
The class of currently available GLP-1s includes Ozempic (semaglutide) and Mounjaro (tirzepatide), which are prescribed for type 2 diabetes, and Wegovy (semaglutide) and Zepbound (tirzepatide), which are prescribed to treat being overweight and obesity.
The drugs’ impact on other diseases besides diabetes and obesity have been observed in clinical trials and in people taking the medications in the “real world” — but questions remain if GLP-1s are safe and effective in treating these other conditions. Here’s a rundown of how the drugs that are being studied and what researchers hope to discover.
GLP-1s for Heart Disease and Stroke
Cardiovascular outcome trials with several GLP-1 drugs have shown impressive improvements in reducing major adverse cardiovascular events like heart attacks, strokes, and cardiovascular death, says Isaacs.
That would be expected, given that obesity and being overweight are risk factors for heart attack and stroke. But other drugs and lifestyle interventions, despite showing glucose lowering and weight loss, have not demonstrated these types of impressive results, Isaacs points out. “This indicates that there are mechanisms that go well beyond just weight loss or glucose lowering,” she says.
That was shown in the Wegovy weight loss trial SELECT, where people taking the drug had a 20 percent lower incidence of heart attack, stroke, or death from heart disease compared with placebo, says Ard.
Much of the reduced risk could be a result of weight loss, but the weight loss in the SELECT trial wasn’t especially large — around 8 to 9 percent on average of each participant’s body weight, he says. “This leaves open the question that there may be some other primary effect that is yet to be determined,” says Ard.
The SELECT trial is the first time a drug used for obesity has shown a cardiovascular disease reduction in a large, randomized controlled trial, says Isaacs. “This may change the paradigm of how we view overweight and obesity (as a cardiovascular risk factor and not just a cosmetic condition) and will hopefully expand coverage and access for these medications for weight loss,” she says.
The trials evaluating cardiovascular benefits of GLP-1 medications include one for tirzepatide in people with obesity and heart failure, expected to be completed by July 2024, and one for semaglutide along with mechanical removal of clots in patients with strokes caused by the blockage of large blood vessels to the brain compared with standard therapy.
GLP-1s for Alzheimer’s Disease and Parkinson’s Disease
Two clinical trials, Evoke and Evoke+, are testing the potential neuroprotective benefits of semaglutide in patients with early Alzheimer’s disease. Preliminary findings could be published as early as 2025.
Although the GLP-1 drug lixisenatide (Adlyxin) isn’t currently available in the United States, per the U.S. Food and Drug Administration, preliminary results of a one-year study suggest that the drug may slow the progression of motor symptoms in early Parkinson’s disease. The complete findings are expected in early 2024.
If current and future studies find reasonable clinical evidence of some effect for GLP-1s for these types of conditions, the biggest potential impact may be in the prevention space or in slowing progression of mild cognitive impairment, says Ard. “There may also be a role of using these medications in combination with other therapies that target amyloid deposition,” he says.
GLP-1s for Addictive Behaviors Such as Alcohol Use Disorder and Smoking
Research has provided evidence that GLP-1s may reduce alcohol cravings and help people with alcohol use disorder drink less. A small case series that examined the medical records of people on semaglutide for weight loss found a significant reduction in the symptoms for alcohol use disorder in all six people taking the medication.
A prospective six-month study is currently investigating whether treatment with semaglutide helps reduce alcohol intake in 108 people diagnosed with alcohol use disorder and obesity.
There’s also evidence that GLP-1s may reduce the use of addictive drugs, including nicotine. Research is comparing the effectiveness of semaglutide to placebo in helping people kick the cigarette habit.
GLP-1s for Sleep Apnea
Tirzepatide is being studied in treating obstructive sleep apnea in both people who use a C-PAP machine and in people who are unable or unwilling to use the machine. The phase 3 trial is set to finish in spring 2024 with results published later that year.
GLP-1s for Liver Disease and Kidney Disease
Researchers are testing semaglutide in a late-stage trial of 1,200 people with a type of fatty liver disease called nonalcoholic steatohepatitis (NASH). Tirzepatide is also being evaluated in a Phase 2 study of nearly 200 NASH patients.
In the FLOW trial, semaglutide was shown to delay the progression of chronic kidney disease (CKD) and lower the risk of kidney and cardiovascular mortality. Research is also evaluating tirzepatide in people who are overweight or obese and have CKD, with or without type 2 diabetes.
GLP-1s for Osteoarthritis
GLP-1 drugs may impact the disease process in osteoarthritis, according to a study published in July 2023 in the Annals of the Rheumatic Diseases. Researchers found that people on the drugs lost more weight and had fewer knee surgeries than people not taking a GLP-1.
Researchers are currently recruiting participants who are overweight and have knee osteoarthritis to prospectively test the efficacy and safety of an experimental GLP-1 from Eli Lilly, retatrutide.
GLP-1s for Polycystic Ovary Syndrome (PCOS)
Women with PCOS produce excess testosterone, which can lead to painful, heavy, or irregular periods, infertility, excess facial and body hair, severe acne, and small cysts on the ovaries. This hormonal imbalance can also cause metabolic complications.
A study published in August 2022 in Fertility and Sterility found that the GLP-1 liraglutide helped reduce elevated testosterone levels significantly and was superior to placebo in treating all adverse symptoms in women with PCOS and obesity.
GLP-1s for Colorectal Cancer and Cancer-Fighting Cells
GLP-1 drugs could reduce the risk of colorectal cancer, according to a large retrospective study of people with type 2 diabetes published in December 2023 in JAMA Oncology. The lower risk was found in both people with overweight or obesity and people without.
There’s also evidence that GLP-1 medications may help restore function in the “Natural Killer” (NK) anticancer immune cell. An Irish study found that the restored cancer-killing effect of the NK cells was independent of the GLP-1’s main weight loss function, leading researchers to conclude that the drugs directly kick-start the NK cells’ engine.
We know that when people lose weight, it also affects immune function, says Matthew Ringel, MD, director of the division of endocrinology, diabetes, and metabolism at The Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute.
“It would be intriguing if GLP-1 agonists directly affect how well the natural killer cells work,” says Dr. Ringel. Larger prospective studies with the risk of developing different types of cancer as an endpoint would need to be conducted to confirm this theory, he says.
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