Surprises and Concerns About GLP-1 Medications

Glucagon-like peptide-1 medications (GLP-1s) were originally developed to treat diabetes. GLP-1s help the pancreas make more insulin, to counteract the insulin-resistance that happens with diabetes.

But researchers got a surprise when they discovered people taking GLP-1s were losing weight and reporting feeling fuller. The surprises keep coming – both welcome and worrisome. GLP-1s may have applications for treating heart disease, PCOS, menopause and more. But they could also contribute to bone and muscle loss or eating disorders.

Physicians and researchers came together to answer some of these questions and concerns.

In general, patients must be diagnosed with diabetes or meet BMI criteria to be prescribed a GLP-1 medication, such as Ozempic, Mounjaro, Wegovy, Zepbound and Saxenda.

“It's basically someone with a BMI of 27 to 29.9 with a comorbidity, something related to their weight, or if they have a BMI over 30,” says Johanna Finkle, MD, OB-GYN physician at The University of Kansas Health System. “Like high blood pressure, diabetes, high cholesterol, sleep apnea, if they have one of those conditions, plus a BMI over 27 they qualify for the medications.”

“The drug seems to affect satiety, so it makes you more full,” says John Thyfault, PhD, leader of KC-MORE. “It also slows down the gastric emptying, so one of the reasons it makes you stay full is your stomach doesn't process the nutrients as quickly, and the whole digestive process slows down a little bit.”

While that slower gastric emptying improves satiety, or the feeling of fullness between meals, it also has the side effects of nausea, vomiting, diarrhea, constipation and heartburn.

“When we lose weight, we don’t just lose fat,” says Dr. Finkle. “We lose water, and we lose lean muscle mass.”

She says there is also a concern about maintaining bone density, especially for older women taking GLP-1s. She recommends some form of strength training or resistance training to help maintain muscle mass.

“So the research right now is suggesting that it may cause some muscle loss,” says Dr. Finkle. “We're trying to preserve at least 30% lean muscle mass, and strength training really helps with that.”

These drugs may be helpful for treating some symptoms of menopause, but Thyfault says it needs more research.

So it’s important for women in menopause to combine medication therapy with lifestyle changes.

“There's evidence, in some studies, that they have effects in reversing the effects of polycystic ovarian syndrome,” says Dr. Finkle. “More research is needed.”

Those studies have shown that after taking a GLP-1 drug, people with PCOS ovulate more and their cycle becomes more regular. Also, fertility and natural conception is increased.

“There's GLP-1 receptors on our ovaries, on our endometrium, so there's some preliminary evidence, at least on animal data, that it does help with implantation, making the endometrium healthier, decreasing inflammation,” says Dr. Finkle.

There are positive effects of GLP-1 drugs on the cells that line your blood vessels. Some clinical trials show they help regulate blood pressure and lower mortality of those who had previously had a cardiovascular event or cardiovascular disease.

However, Thyfault says it’s unclear if that’s a credit to the GLP-1 or a benefit of losing weight overall.

They can.

“It works through the parasympathetic nervous system, a part of your nervous system, and it also affects the vagus nerve, and so it can increase people's heart rate,” says Dr. Finkle.

Thyfault explains that one study of 17,000 individuals showed that 62 people not taking a GLP-1 died from COVID-19 while 42 who were taking a GLP-1 died from COVID-19. That makes it statistically significant, but he cautions against drawing too many conclusions.

“It probably had to do with the weight status,” Thyfault says. “People who are obese have a chronic inflammatory status that's a little bit elevated. Their cardiopulmonary function is usually not as good. COVID works through those mechanisms and really affects the ability to get oxygen into the system and distribute it. So having a little bit of weight loss probably did protect those people.”

Katy Harvey, a registered dietitian, says the eating disorder field is generally very concerned about the increasing usage of GLP-1 medications.

“We don't want people abusing these drugs to lose weight who don't need to be on them or using it to become malnourished,” she says. “Of course, we don't want to be making those types of eating disorders worse.”

However, she pointed out that they can be beneficial for some people.

“We're seeing a lot of people reporting that it decreases the food noise. With eating disorders, it's essentially this constant chatter in the brain that is thinking about, what am I going to eat later? What did I already eat? How many calories have I had? And so with these drugs, it's like we're quieting that down, and they can finally listen to their body and make decisions that are more attuned to what their body actually needs.”

GLP-1s may be especially helpful for those with binge eating disorders. Harvey explained that strong compulsions around eating are often correlated with diabetes, prediabetes, PCOS and cardiac disease, too.

“We've got a lot of overlap here with the things that these drugs treat and binge eating disorder, and what I'm seeing in my clinical practice is that the drug is helping people in really meaningful ways with their health,” says Harvey. “It's helping them with their eating disorder because they're able to stop eating much more easily, and they're not having as many binge episodes.”

Research shows that GLP-1s can decrease not only food cravings, but desire for things like alcohol and other substances. Harvey says there may be utility there.

Currently, yes. However, Dr. Finkle said there are oral GLP-1 drugs on the horizon.

“That'll open up the door for patients that aren't able to have the injectables and open up the market a little bit, because we are having some supply issues,” says Dr. Finkle. “Providing more options is really what we want.”