At 5 feet 11 inches and 138 pounds, Ali Balkey has always been thin.

So it might seem surprising that the 41-year-old Dallas, Texas real-estate investor says she has been taking a compounded version of a GLP-1 since February.

It is most certainly not for weight loss. Balkey says she takes a microdose-a smaller amount than what's normally prescribed-to help her manage pain and other symptoms from endometriosis, an inflammatory condition in which tissue becomes implanted outside the uterus, causing scarring, adhesions and pain.

Long used for weight loss and diabetes, the Food and Drug Administration has approved certain GLP-1s for additional uses, including obstructive sleep apnea, chronic kidney disease and severe fatty liver disease. Though widely considered safe for most people, the drugs can have side effects, such as gastrointestinal issues, muscle and bone loss and rare serious conditions like pancreatic inflammation. But the GLP-1s are increasingly being researched, used experimentally, and even prescribed off-label to treat a range of other conditions in which they show promise.

Dr. Andrea Vidali, a prominent endometriosis surgeon who works in Florida and New York, estimates that nearly one in five of his endometriosis patients, like Balkey, take a GLP-1 off-label, some prescribed by him and some who come in already taking them, mainly for pain and related symptoms.

Like most doctors, he only prescribes brand-name GLP-1s made by Eli Lilly and Novo rather than the compounded, copies versions made by special pharmacies and commonly sold by telehealth companies and med spas. When the brand-name drugs are prescribed off-label, they aren't covered by insurance and can cost hundreds of dollars a month. But because patients are microdosing, one $499 Ozempic pen goes much farther, bringing the monthly cost well below that, says Vidali.

"I usually keep them on the microdose," says Vidali. "Many of these patients are not overweight, some are normal weight or even underweight, so you don't want them to lose weight or muscle mass."

The GLP-1s aren't treating the actual disease, says Vidali. Rather, their likely target is a nerve and immune system that has become oversensitized, he says.

"Mechanistically, the hypothesis is that it works in the periphery, with an anti-inflammatory effect on the nerves," he says.

Vidali says prescribing GLP-1s off-label is becoming more mainstream, particularly in fertility practices, for women with polyendocrine metabolic ovarian syndrome, or PMOS, and related metabolic issues such as insulin resistance. Novo and Eli Lilly don't support the off-label use of their GLP-1 medications.

Some studies conducted by academic researchers suggest GLP-1s may improve metabolic health and menstrual regularity in women with PMOS, particularly those who are overweight or have obesity. Patients with irritable bowel syndrome who took an experimental GLP-1 drug reported relief of acute pain and those with knee osteoarthritis and obesity have less knee pain though that can't be separated from weight loss.

While the evidence is still preliminary, or in some cases anecdotal, demand to try a GLP-1 is high.

Dr. Diana Girnita, founder and CEO of Rheumatologist OnCall, a telemedicine practice in more than 20 states, has seen patients with conditions like rheumatoid arthritis, gout, psoriasis, and knee and hip osteoarthritis seek out GLP-1s. She estimates about 10% of the practice's nearly 2,000 patients are on a GLP-1, with only a fraction of them using them truly off-label because they don't have obesity or Type 2 diabetes.

Of her patients who take GLP-1s for such conditions, nearly 80% report less joint pain and better function, she said, though it can take three to six months for patients to see improvements in symptoms.

In patients who aren't overweight, she is cautious, typically starting them on a six-month trial of a microdose. "What I watch for is lean mass loss, which matters more in someone with inflammatory arthritis than in the general population, because muscle is what protects the joint," she says.

Dr. Louis Cohen, a gastroenterologist and associate professor at Mount Sinai in New York City, is studying whether tirzepatide-the active ingredient in Eli Lilly's Zepbound and Mounjaro -can improve symptoms in patients with Crohn's disease, a type of inflammatory bowel disease. He's enrolling mostly normal weight patients in a small trial that will compare taking a GLP-1 with standard of care over six months.

Participants are taking standard doses of tirzepatide-not microdoses. They work closely with a nutritionist to monitor their weight and calorie intake.

"People sort of forget what GLP-1s are fundamentally," says Cohen. "They promote absorption within the bowel so they slow down movement within the bowel but they also may stimulate the bowel to grow."

While there is a decent amount of data showing that Crohn's patients can tolerate GLP-1s, Cohen says he's not yet prescribing them off-label for patients who don't meet the criteria. He's holding off until he sees trial data but is encouraged by reports that GLP-1s helped improve outcomes in patients with psoriasis, which has similar medical characteristics to Crohn's.

While doctors and researchers explore GLP-1's potential for other conditions, getting those uses approved can be challenging. Drug companies generally have to sponsor large clinical trials to receive FDA approval for additional indications, and insurers don't typically cover a drug until it is FDA approved.

And while promising, some doctors are still cautious about off-label prescribing. Dr. Katherine H. Saunders, a clinical assistant professor of medicine at Weill Cornell Medicine and co-founder of FlyteHealth, a medical obesity-treatment company, says while she's open-minded, she is not cavalier about prescribing GLP-1s for off-label use.

"The further we move from an FDA-approved indication, the higher the bar should be," she says. "These are powerful medications, and enthusiasm should not get ahead of science."

For most conditions, the evidence remains scarcer than it is for obesity, diabetes, and the other conditions for which GLP-1 drugs have been approved. One of the most compelling off-label uses of GLP-1s is in patients with alcohol use disorder and other addiction disorders, says Saunders.

A spokesperson for Eli Lilly said the company is studying additional uses for GLP-1s, including to treat substance abuse disorders, heart disease, asthma, and other neurological and immunologic conditions. A spokesperson for Novo said the company isn't currently studying any additional uses for the GLP-1 medications on the market.

Balkey says she started taking GLP-1 after an endometriosis surgery with Vidali in January. Vidali mentioned that many of his patients were noticing improvements with a GLP-1.

"I had never really considered it because I have a low BMI," Balkey says. She was nervous because she gets nauseous easily but hasn't experienced any negative side effects.

"I'm the same weight," she says. "I am intentional about making sure I'm eating enough and getting my protein."

Balkey says she started seeing improvements in her symptoms within about two months, though acknowledges some of it is also attributable to the surgery.

"My life has dramatically improved," she says. "I hope that we're able to get funding for more research so that this type of treatment can be available."