Erin Gardiner, 71, has had migraine attacks for more than 30 years. Most of the time she manages them with over-the-counter pain relievers. On occasion they've been so bad she's had to retreat to a bedroom, close all the blinds, and put a pillow over her head, says Gardiner, a retired school administrator outside San Francisco.
But three months ago when she started taking tirzepatide (Zepbound), a weight loss drug, the attacks disappeared. “I got a migraine right around the time I started the drug, and I was scared I was having a reaction to the medication,” she says. “But my primary care provider reassured me it wasn't on the list of side effects. She thought it may have been due to my feeling stressed about starting the medication, especially since I was injecting it on my own at home.”
So far, Gardiner has lost 12 of the 60 pounds she hopes to lose (and keep off this time) and has not experienced a single additional headache. It's not clear if it's because she's lost weight or been more active or if the drug is somehow helping her headaches. “Whatever the reason, I'm thrilled that two of my health issues—being overweight and having migraine attacks—are resolving,” she says.
New medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are being marketed for their ability to help people manage type 2 diabetes and lose weight. (Ozempic and Wegovy are both made by Novo Nordisk, but Wegovy is approved for weight loss, while Ozempic is approved specifically for type 2 diabetes. Mounjaro and Zepbound are both made by Lilly; the former is approved for type 2 diabetes, the latter for weight loss.)
These drugs, known as glucagon-like-peptide-1 (GLP-1) receptor agonists, activate important hormone pathways to help control blood sugar levels and reduce appetite, thus leading to weight loss. Now there is tantalizing new research to suggest that they also may help treat or even prevent neurologic disorders such as stroke, diabetic neuropathy, multiple sclerosis (MS), and even Alzheimer's disease.
“These drugs have revolutionized the treatment of obesity, and research also shows that when we use them in people with diabetes, we see a reduced risk of heart attack, stroke, and kidney disease,” says Brian Callaghan, MD, FAAN, professor of neurology at the University of Michigan in Ann Arbor. Initial studies suggest promise for treating neurologic diseases, “but it's not clear if the drugs act on the brain itself or if the protective effects come from weight loss,” he says. “We need more large studies to get a sense of how these drugs may affect brain function.”
Latest Research
GLP-1 receptor agonists like semaglutide have an anti-inflammatory effect on the brain, which may be how they help reduce the risk of neurologic conditions, says Gary Small, MD, professor and chair of psychiatry at Hackensack University Medical Center in New Jersey. Or the reduced risk may be because of the weight loss itself, he says. “We know that fat cells, especially those that are visceral fat (which is the fat deep in the belly, nestled around the organs), have inflammatory compounds,” says Dr. Small, who specializes in treating dementia. “When you lose weight, some of the hyperinflammation from those fat cells is diminished.” A study published in JAMA Network Open in 2024 suggests that the benefit may come from losing weight. Researchers followed 133 adults with severe obesity who underwent bariatric surgery. Brain scans done over a two-year period found changes in brain structure and function and health benefits such as lower inflammation in blood tests, greater physical activity, and lower depressive symptoms.
But GLP-1 receptor agonists may promote the survival and growth of brain neurons as well as inhibit the death of brain cells, Dr. Small adds. They also may help deliver oxygen and other nutrients to brain cells, as well as assist in controlling neurotransmitters such as glutamate, GABA, and dopamine, which are involved in mood, according to a review of animal and cellular studies in the International Journal of Molecular Sciences.
So far, studies suggest that GLP-1 receptor agonists may one day be useful for treating the conditions discussed in the sections that follow. For now, however, the U.S. Food and Drug Administration (FDA) has not approved these drugs for anything other than type 2 diabetes and weight loss. “While the data are promising, there are no indications that people with neurologic conditions should take GLP-1 medications to treat their diseases,” cautions Barbara Giesser, MD, FAAN, a neurologist at the Pacific Neuroscience Institute in Santa Monica, CA.
Peripheral Neuropathy
“Peripheral nerves send messages between the central nervous system, or brain and spinal cord, and other parts of the body,” explains Dr. Callaghan. “But certain conditions, like diabetes, can damage peripheral nerves and make it harder for them to send signals.” As a result, people with diabetes may experience numbness, tingling, and loss of sensation in their hands and feet.
A small study published in the medical journal Diabetologia in 2024 found that two GLP-1 receptor agonists—semaglutide and dulaglutide (Trulicity)—improved nerve structure and function among subjects with diabetic neuropathy. The study, which looked at 22 people with diabetes, found that most patients had an abnormally large tibial nerve, which provides sensation to the back of the leg and foot. After just a month of treatment, more than 80 percent saw this nerve shrink, and in almost a third it returned to normal size. Three months later, virtually all of the 14 patients who were still being followed demonstrated continued improvements in nerve size as well as a reduction in neuropathic symptoms.
These results are exciting but preliminary, cautions Dr. Callaghan. In a previous study published in the Journal of Diabetes and Its Complications in 2015, Dr. Callaghan and his colleagues followed 46 patients with diabetes who took exenatide (Byetta), another GLP-1 receptor agonist, for 18 months and found that those patients didn't control their blood glucose levels or symptoms of diabetic neuropathy better than patients who took insulin.
Migraine
No published studies have found a link between taking GLP-1 receptor agonists and a reduction of migraine attacks. Anecdotally, they may seem to alleviate episodes in patients like Gardiner because of the weight loss, changes in diet, or by avoiding dietary triggers. Being overweight, especially being obese, is a risk factor for episodic migraine becoming more severe, harder to treat, and chronic, says Alan Rapoport, MD, FAAN, clinical professor of neurology at the David Geffen School of Medicine at UCLA. Early animal research also hints that the GLP-1 receptor agonists may help the brain handle a migraine attack better. One small study in mice published in 2023 in Neuroscience Letters found that the GLP-1 receptor agonist liraglutide (Victoza 2-Pak) stimulates the release of IL-10, a chemical in the brain that helps reduce inflammation. “As a result, you become less sensitive to pain,” says Dr. Rapoport.
Semaglutide may be especially effective for idiopathic intracranial hypertension (IIH), a headache caused by increased pressure in the brain due to a buildup of cerebrospinal fluid, the liquid that nourishes, protects, and removes waste from the brain. While IIH can happen to anyone, it's much more common among people, especially females, who are obese, says Dr. Rapoport. A small randomized clinical trial of 15 women published in Brain in 2023 found that those who took exenatide had a reduction in intracranial pressure and nearly eight fewer headache days over three months than those who got a placebo.
Another small study published in the Journal of Headache and Pain looked at 39 people with IIH, a third of whom were being treated with GLP-1 receptor agonists like semaglutide or liraglutide. People in the GLP-1 receptor agonist group not only lost more weight but had about four fewer headache days a month compared with those in the control group.
An indirect cause of fewer attacks may be that weight loss decreases sleep apnea, which is linked to morning headaches, says Louis J. Aronne, MD, an obesity specialist at Weill Cornell Medicine in New York City.
Multiple Sclerosis
Neurologists have long seen an association between weight loss and a reduction in symptoms of MS, says Dr. Giesser. “Obesity itself is a risk factor for developing the condition and is associated with worse neurologic outcomes,” she says. “It may be that at least some of the GLP-1 receptor agonists' apparent effect is indirect and comes from reducing obesity.”
Other MS experts agree. “Our MS center has a handful of patients taking GLP-1 receptor agonists. We often see a reduction in symptoms and an improvement in daily functioning among those who have had a fairly dramatic weight loss through dieting, exercise, and sometimes bariatric surgery,” says Dennis Bourdette, MD, FAAN, professor emeritus of neurology at Oregon Health & Science University in Portland. “Losing weight improves energy, strength, and balance and helps prevent injury to joints caused by obesity.”
A 2024 report published in Therapeutic Advances in Neurological Disorders that looked at data about weight loss drugs like semaglutide, dulaglutide, and liraglutide found that MS occurred less often in people taking these drugs, perhaps because of the medications' anti-inflammatory effect while reducing obesity. Other diabetes drugs such as empagliflozin and metformin showed a similar effect. “It's very possible that these medications do more than just help people with diabetes control their blood glucose better and lose weight—they may have anti-inflammatory and possibly even neuroprotective effects,” says Dr. Bourdette. Other research done in mice found that GLP-1 receptor agonist drugs helped reduce the severity of MS-like symptoms.
But these studies show only an association, not a cause and effect, warns Dr. Bourdette. No clear conclusions can be drawn until larger well-designed studies have been completed.
Parkinson's Disease
GLP-1 receptor agonists may protect against Parkinson's disease or ease its symptoms by tamping down inflammation and opening up blood vessels that lead to the brain, says Dr. Bourdette. A small study in the Lancet in 2017 found that people with Parkinson's disease who received weekly injections of exenatide had less severe motor disability than a control group. An earlier study published in the Journal of Clinical Investigation found similar results. More research needs to be done to see if other GLP-1 receptor agonists have the same effects. One concern, according to the study authors, is that some of the other drugs may not cross the blood-brain barrier so well as exenatide.
Stroke
There's so much strong evidence that GLP-1 receptor agonists help reduce the risk of stroke among people with type 2 diabetes that many guidelines, including those from the American Heart Association, recommend that people with type 2 diabetes take the drugs in addition to getting regular exercise, eating healthfully, quitting smoking, and avoiding alcohol.
A study published in the New England Journal of Medicine in 2023 found that people who were overweight or obese and had preexisting cardiovascular disease—but not diabetes—significantly reduced their risk of heart attack and stroke when they took semaglutide compared with people who took a placebo. A study published in the journal Lancet, Diabetes & Endocrinology in 2020 looked at more than 9,900 patients with both type 2 diabetes and either heart disease or risk factors for it and found that people who took dulaglutide had a 25 percent lower risk of ischemic stroke.
In March 2024, the FDA approved semaglutide injections to reduce the risk of stroke in all people with cardiovascular disease who were also overweight or obese. “Excess weight is a major risk factor for stroke, and semaglutide helps with weight loss,” says Dr. Aronne, who is director of the Comprehensive Weight Control Center at Weill Cornell Medical Center in New York City. “It also helps with other risk factors for stroke, including high blood glucose levels, high blood pressure, and inflammation.”
Dementia
People with diabetes who take semaglutide appear to have a lower risk of dementia, according to a 2024 University of Oxford study published in eClinicalMedicine. Scientists combed through more than 100 million patient records to find about 20,000 patients who took semaglutide, then compared them with patients who took other diabetes medications, such as sitagliptin (a type of drug known as a dipeptidyl peptidase-4 inhibitor). Patients on semaglutide reduced their risk of developing cognitive problems by almost 30 percent and dementia by almost half. One theory, based on looking through the patients' records, is that these drugs may prevent the buildup of amyloid (a protein linked to the development of Alzheimer's) in the brain, says Dr. Small.
Novo Nordisk, the company that sells semaglutide, has begun testing the medication in thousands of patients with early Alzheimer's disease, with results expected in 2025.
Price Considerations
These new drugs can cost up to $1,400 out of pocket per month, says Dr. Callaghan. And while most insurance companies will cover them for people with type 2 diabetes, patients usually have to try—and fail—a few other diabetes treatments first, he adds. Because of that, “the drugs may not be ready for treating patients with neurologic disease just yet unless the patients have an underlying condition such as heart disease or type 2 diabetes,” says Dr. Callaghan. For these patients, adopting healthy habits such as reducing calories and staying as active as possible may be the best option.
But for some people, trying a GLP-1 receptor agonist may be appropriate. Erin Gardiner says she struggled for years with yo-yo dieting. Six years ago, she lost 60-plus pounds, only to gain most of it back during the pandemic. Then, when her son got into an accident that left him paralyzed from the chest down, “the stress made me gain 30 pounds in a year,” she says. “I didn't want to go back on a restrictive diet where I constantly fought hunger pangs and in general made myself miserable.”
Gardiner doesn't know if it's the medication that's reducing her migraine episodes or the fact that she's taking better care of herself. “I'm focused now on regular exercise, a high-fiber, high-protein diet, and drinking plenty of water,” she says. “I feel much better and can move much more easily when I'm lighter. Does that mean I'll stay on the drug forever? I don't know. I take it one day at a time.”
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