Physician cautions about possible long-term effects of GLP-1 weight loss medications

Weight-loss drugs such as Ozempic and Wegovy have changed how many Americans approach obesity treatment, helping patients achieve major results. As their use grows, however, doctors are continuing to examine how safe they are over the long term and whether some side effects could linger after treatment ends.

GLP-1 medications have become an important option in treating obesity, a condition tied to serious health concerns including heart disease, Type 2 diabetes and several cancers.

Research has shown that these drugs can produce significant weight loss and other health gains, but questions remain about what may happen after years of use and how side effects should be handled.

Dr. Joseph Varon, president and chief medical officer of the Independent Medical Alliance, spoke with The National News Desk about the benefits, risks and longer-term questions surrounding GLP-1 medications.

“The history of medicine teaches us that we must distinguish between what we know and what we're yet to know,” Varon said.

He noted that obesity itself carries substantial health risks, including a higher chance of developing certain cancers.

“We know that obesity increases the chance of having cancer in 13 different types of cancers,” Varon said.

According to the Centers for Disease Control and Prevention, excess body weight is linked to a higher risk of at least 13 cancers, including colorectal, kidney, liver and endometrial cancer.

Varon acknowledged that GLP-1 medications can help many patients lose considerable weight, which may reduce some of the risks associated with obesity.

Still, he said researchers are continuing to study the long-term effects of drugs that are now widely prescribed for weight management.

“What we don't know is the safety data from decades of these medications,” Varon said.

He pointed to animal research involving some GLP-1 drugs that raised concerns about a particular type of thyroid cancer.

“We know, for example, that in animal models there is an increase in the type of thyroid cancer that you can see,” Varon said.

Some GLP-1 medications include an FDA boxed warning about thyroid C-cell tumors seen in rodents. It is still unclear whether those findings translate into a higher risk of medullary thyroid carcinoma in people.

These medications are generally not recommended for patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

Varon said his concerns go beyond the cancer questions raised by animal studies.

He said he has seen patients in his own practice deal with persistent gastrointestinal problems after stopping GLP-1 treatment.

“I have seen a lot of long-term complications in people that went on a GLP-1 even after they stopped the GLP-1,” Varon said.

He described patients who experience severe diarrhea after eating, sometimes long after ending the medication.

“I have patients that anything that they eat will get them to go immediately to the bathroom, that they will have diarrhea,” Varon said.

He said some of those patients had stopped taking the drugs two or three years earlier.

“Even though they have stopped these medications two and three years ago,” Varon said.

Diarrhea, nausea, vomiting and constipation are known digestive side effects of GLP-1 medications. But the interview did not prove that the drugs caused the lasting symptoms Varon described, and evidence that gastrointestinal problems continue for years after discontinuation remains limited.

Varon said these cases are hard to manage because the symptoms can seriously disrupt daily life.

“These medications carry some very serious risks,” Varon said.

He also said gastroenterologists he knows have seen similar cases.

“Even my associates, friends who are gastroenterologists, they said, 'We don't know what to do with these people,'” Varon said.

“We have to give them now medication to prevent them from having to run to the bathroom every time they eat.”

The experiences he described underscore the importance of evaluating ongoing digestive symptoms instead of assuming they are automatically tied to a past medication.

Other digestive disorders, infections and underlying medical conditions can cause similar problems and may need separate evaluation.

Despite his concerns, Varon stressed that GLP-1 medications can be highly effective for treating obesity.

He explained that they work by mimicking hormones that help regulate appetite, blood sugar and feelings of fullness.

“These medications, what they do is they mimic hormones that you normally have in your intestines that communicate with the brain, and they regulate appetite, fullness and blood sugar,” Varon said.

GLP-1 receptor agonists act on hormone pathways that help control insulin release, appetite and digestion.

Semaglutide, the active ingredient in Ozempic and Wegovy, has been shown in clinical trials to deliver substantial weight loss when paired with lifestyle changes.

Varon said patients using semaglutide may lose about 15% of their body weight, while some other medications can lead to reductions nearing 20%.

“We know that, for example, semaglutide can give you 15% weight loss,” Varon said.

“And some of the other agents can bring you down by 20%.”

Trial results differ based on the drug, dose, length of treatment and the characteristics of the people in the study.

Varon said the medications should not be dismissed simply because they also come with risks.

“They are very powerful medications,” Varon said. “I don't dismiss their benefits.”

He added that the rising use of weight-loss drugs should not overshadow the larger need to prevent obesity in the first place.

Pointing to the increase in obesity over recent decades, he said the condition is far more common in the United States than it once was.

“Our genetics haven't changed,” Varon said.

“We have many more people today that are obese than 60 years ago.”

Varon estimated that obesity affected about 13% of Americans decades ago, compared with more than 40% in recent years.

He said the increase reflects a mix of factors, including diet, physical activity, environmental influences, socioeconomic conditions and other contributors.

Varon said the medical community has become better at treating obesity, but should focus more on preventing it.

“We have become very good at treating obesity,” Varon said.

“What we need now to become better at is preventing it. That's what we need to do.”

Another issue is what happens after patients stop taking GLP-1 medications.

Studies have found that many people regain a significant amount of the weight they lost after ending treatment, although the degree varies.

That has prompted questions about whether some patients may need long-term therapy to maintain results.

Varon said patients should understand that lasting weight control often depends on continued attention to nutrition, exercise and other lifestyle habits.

The discussion also covered practical steps that may help reduce gastrointestinal side effects during GLP-1 treatment.

Varon advised eating smaller meals, avoiding especially fatty foods and staying well hydrated.

“One of the things that we have told our patients is, avoid big meals, try having smaller meals, avoid very fatty foods, stay hydrated,” Varon said.

He also stressed that weight loss involves more than just losing fat.

“Understand that when you are losing weight, you are not just losing fat weight, you are also losing muscle weight,” Varon said.

Loss of lean body mass can happen during substantial weight loss, whether it comes from medication, diet or other approaches.

Keeping enough protein in the diet and doing appropriate resistance exercise can help preserve muscle.

Varon said patients should pay close attention to nutrition while taking medications that reduce appetite so dramatically.

“Make sure they take the right amount of protein,” Varon said.

He said the goal should be more than just lowering the number on the scale; it should also be improving overall health while limiting unwanted effects.

The conversation comes as GLP-1 medications continue to expand their role in U.S. health care, with researchers studying their possible benefits for cardiovascular disease, metabolic conditions and other obesity-related complications.

For anyone considering treatment, doctors generally advise discussing expected benefits, possible side effects, personal medical history and long-term plans with a qualified health care professional.

Varon said the drugs provide meaningful benefits, but they should be approached with an awareness of what is still unknown.

“The history of medicine teaches us that we must distinguish between what we know and what we're yet to know,” Varon said.

For him, the larger priority is helping Americans live healthier lives while continuing to assess the long-term safety of increasingly popular treatments.

“We have become very good at treating obesity,” Varon said. “What we need now to become better at is preventing it.”