GLP-1 Medications Keep Advancing and Could Soon Be Used for More Health Conditions

GLP-1 drugs have outlasted many weight-loss fads and appear likely to remain a mainstay. First approved by the Food and Drug Administration in 2005 to treat Type 2 diabetes, these medications are now used by 12 percent of U.S. adults for weight loss, in addition to the 26 percent of adults with diabetes who take them. Forbes has reported that as many as 30 million Americans could be using GLP-1s by the end of the decade.

Most people have heard of GLP-1s, and many know someone who has shed pounds with them, but the term can still be confusing. GLP-1 stands for glucagon-like peptide-1, a hormone made in the gastrointestinal system.

“When food hits the intestine, this hormone signals both the pancreas and the brain that it’s mealtime,” said Dr. Hooman Motahari, an endocrinologist at the Conway Regional Endocrinology and Diabetes Center. “Normally, your body’s version of GLP-1 doesn’t stick around long; it breaks down in about two minutes. However, medications have been developed as modified versions of this hormone, and they last much longer, up to several days. This extended duration is why many of these medications come as weekly injections.”

Motahari said GLP-1s support weight loss in several ways. They help the pancreas release insulin when blood sugar rises, slow stomach emptying so people stay full longer, and act on brain centers that regulate hunger and appetite. That can reduce what some patients call “food noise.”

“Food noise is the persistent mental chatter about food, thinking about your next meal while you’re still eating, feeling distracted by cravings or repeatedly thinking about a snack even when you’re full,” Motahari said. “Some people taking GLP-1 medications describe these thoughts becoming quieter, so they spend less time thinking about food and feel more at ease with their choices.”

There are several versions of the drugs. Ozempic, the semaglutide that helped bring GLP-1s into the spotlight, and Wegovy both act on the GLP-1 receptor alone. A newer option, tirzepatide, works on the GLP-1 receptor and the receptor for GIP, another gut hormone, to better manage appetite and blood sugar. Mounjaro and Zepbound are among the tirzepatide brands.

“It’s kind of like the new and improved version in the class that’s actually approved for use right now,” said Kayla Sanders, nurse practitioner and owner of Beauty Boss Co. “I would say that we’re probably using that more commonly in the wellness space than we are a semaglutide just because our patients are getting a little bit better result, and then less side effects is always a good thing.”

Robert Maltby, owner of Marketplace Pharmacy in Little Rock, said he expects another GLP-1, retatrutide, to be available early next year. In addition to GLP-1 and GIP, it also targets glucagon receptors, which may increase energy expenditure and help patients burn more fat.

Some companies, including Wegovy, have developed oral versions of semaglutide and tirzepatide, but Maltby said the pills are generally less effective than injections.

“The absorption from the injection is so much greater than the absorption from the tablet,” he said. “The tablets have some very strict requirements for it to work efficiently for the patient, but even if done perfectly fine, the patient is only absorbing a very small amount of that tablet, which is why they’re having to take it every single day versus the injections being once a week.”

Maltby said one reason GLP-1s have been so well received is that many older weight-loss drugs, including phentermine, work by stimulating the central nervous system and can produce unpleasant or risky side effects.

“It increases your heart rate, so you have this shakiness or jitteriness that goes along with it,” he said. “If a patient has cardiovascular issues or high blood pressure, then they’re not good candidates for Adipex or for phentermine.”

Another medication, Contrave, combines bupropion and naltrexone to suppress appetite and blunt the reward response from eating, he said, though he added that it has not matched the effectiveness of GLP-1s.

“The most success, I would say, that patients have had has been on the GLP-1s,” he said.

Motahari pointed to research showing that people lose about 15 percent of their body weight on semaglutide and about 20 percent on the highest dose of tirzepatide. He said retatrutide has helped people lose nearly 30 percent at the highest dose.

By comparison, diet and exercise typically produce weight loss of 5 to 10 percent, while bariatric surgery, the most effective option for severe obesity, can lead to a loss of 25 to 30 percent, he said.

“What really matters isn’t just the number on the scale,” he said. “Research involving over 17,000 heart disease patients with excess weight showed that semaglutide cut down the chance of heart attacks, strokes and death from heart issues by 20 percent. This medication also helps with sleep apnea, fatty liver, knee pain and kidney problems.”

Not everyone should take the drugs, however. People with a personal or family history of medullary thyroid cancer should avoid GLP-1s, and extra caution is needed for patients with a history of pancreatic inflammation or slow digestion.

“They do not work for everybody,” said Dr. Lewis Porter, general and bariatric surgeon at Saline Health System. “GLP-1s are not magic. They are a very powerful tool, just like surgery, but just like any tool, if used inappropriately, you will not get the desired result.”

Porter said whether the drugs are appropriate depends on a patient’s personal situation and other health conditions. The most common side effects are nausea and vomiting, which he said can often be reduced by starting with the lowest dose and eating a healthy diet.

“A lot of the nausea and vomiting that’s brought on by GLP-1s is caused by eating the wrong foods, such as very fatty foods, or by overeating,” he said. “A patient has to learn not to overeat, not to eat the wrong foods, and again, like I said, a very graduated increase in dosage of the medication.”

He said he also recommends nutritional counseling for patients starting GLP-1s, both to support weight-loss goals and to limit side effects.

Exercise remains important for people using the medications, not only for weight loss. Motahari said nearly 40 percent of the weight lost on semaglutide may come from muscle and other tissue rather than fat alone.

“If you’re taking these medications, focus more on maintaining muscle rather than just burning calories,” he said. “Include protein in every meal, and do strength training a couple times a week. Since your food intake decreases, every bite counts more.”

Porter emphasized that losing weight with GLP-1s or surgery instead of diet and exercise alone is not an easy shortcut. He said these medicines are life-saving tools for treating a disease process, much like high blood pressure or another chronic condition.

“There’s nothing about this weight loss journey in any of these patients that is easy,” he said. “Paying that amount of money and being monitored like that and having to give yourself shots, it’s definitely a misconception that that’s easy because there’s nothing easy about that.”

It is often claimed that people regain all the weight after stopping GLP-1s, but Sanders said that does not happen when the medications are used the right way.

“We have had pretty great success with maintenance for our patients at our practice, and the steps that we’ve taken are making sure that our patients are not losing too much too fast, making sure that they understand how important it is to get appropriate nutrition while they are on the GLP-1s,” she said. “If we do those things, they have much better success at maintaining their weight.”

She said the length of treatment varies from person to person. Some patients reach their goal and keep the weight off on their own, while others need maintenance doses. Factors such as menopause and perimenopause can also play a role, and she recommended lab work to check for underlying issues that may affect weight.

“The biggest misconception is that it’s a magic bullet or cure-all and it’s going to be a very, very quick fix,” she said. “We try to make sure we do things the right way and keep everyone as healthy as possible in our office, so it doesn’t always work out that way. Sometimes it is a long game. I think a lot of people come in thinking that they’re going to lose a massive amount of weight really quickly, and that’s just not always the best way to do that.”

She also said she is hopeful about the drugs’ potential use for inflammatory conditions and polyendocrine metabolic ovarian syndrome, or PMOS, formerly known as polycystic ovary syndrome, which may soon be added to the list of approved uses.

“You’re talking about a very large group of women that are affected by that diagnosis, and it affects their life greatly from the time that they’re really young throughout adulthood and even dealing with fertility concerns,” she said. “We have seen patients that have diagnoses of PCOS or PMOS that have had difficulty getting pregnant and fertility issues, but then they’re placed on something like Mounjaro and are able to have regular cycles and are able to get pregnant.”

Porter said weight loss may be one of the more trend-driven parts of wellness, but GLP-1s are likely to remain part of his practice for the long haul.

“I think they’re good medications,” he said. “Anytime we see something new for weight loss, it’s going to be a continuous cycle. I think that the popularity will slow down. It will drop off some, but I think there will always be a subset of patients that can benefit from being on a GLP-1, especially those patients who have other disease processes.”