The obesity drug revolution

The obesity revolution

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) drugs have become pharmaceutical blockbusters for treating type 2 diabetes, helping to regulate the internal metabolic reactions of patients. The drugs also altered something that for some patients is much more visible: body mass index (BMI), the number based on a formula to determine healthy weight, overweight and obesity.

Upon further review and approval by the FDA, Novo Nordisk’s Ozempic earned approval as Wegovy for weight loss, while Eli Lilly and Company’s Mounjaro is marketed as the antiobesity medication Zepbound.

If you are a primary care physician who has not had a patient ask about these drugs, you most likely will soon. Expert physicians who spoke with Medical Economics agreed that short of an unforeseen, calamitous effect on human health, the GLP-1 RAs are not going away.

What do primary care physicians need to know?

“The first thing is to not be afraid to use these drugs,” said Sharon J. Herring, M.D., M.P.H., a professor of medicine at Lewis Katz School of Medicine at Temple University and researcher at the Center for Obesity Research and Education at Temple University College of Public Health. “They can work, patients really like them, and I don’t see stopping them because of side effect issues. I think that most people will continue them.”

What doctors are prescribing GLP-1s?

Most internal medicine and family medicine doctors may already be working with the drugs. In fall 2024, a Medical Economics survey found that 78% of respondents had prescribed GLP-1 RAs to treat obesity. In that poll, 39% of physicians said patients inquired about the medications at least weekly, and 48% received daily patient questions.

Patients are asking about the drugs when they speak with their primary care physicians, as well as specialists in cardiology, obstetrics-gynecology, endocrinology and even orthopedics, said Robert Kushner, M.D., professor of medicine and medical education at Northwestern University Feinberg School of Medicine and a decades-long researcher on overweight, obesity and nutrition.

Patients’ No. 1 question is, “Am I a candidate?”

“You then address that, then you get into more details: What can you expect from them? How much weight loss? How do you manage the side effects? Is it covered by your insurance?” Kushner said. “All these questions that are necessary to follow up on. But ‘Am I a candidate?’ is by far the most common question.”

Not every patient is a good candidate. But for now, the answer for most is “probably, yes.” The drugs are advised for patients with a BMI of 30 or more or a BMI of 27 and a complication such as diabetes, hypertension, high triglycerides or sleep apnea.

“So that is really a low bar to be a potential candidate for these medications if you think about a typical patient, a typical individual in the United States,” Kushner said.

The ‘typical’ patient

In the Medical Economics poll, 83% of respondents said their patients met the criteria for overweight or obesity indicated in the labeling of the medications. Another study dived into detail on patients.

Based on a 2019 to 2023 sample, a typical patient using GLP-1 RA drugs was a White female with a mean age of 54, a BMI of 30 or more and hypertension (61.4%) or type 2 diabetes (57.1%).

“10 years ago, 12 years ago, it was mostly used]for diabetes,” said coauthor Ali Rezaie, M.D., M.Sc., an internal medicine physician who is medical director of the GI Motility Program at Cedars-Sinai as well as director for the Bioinformatics and Biotechnology, Medically Associated Science and Technology Program. “Now the percentage of that indication is dropping, and [the number of] people with no diabetes but obesity and being overweight with some sort of complication of overweight is increasing, and that’s what’s dramatically rising. And that’s kind of expected, but it was good to see that in numbers.”

Doctors are prescribing GLP-1 drugs for non-FDA indications, such as for people who have a normal BMI and no diabetes –– possibly for cosmetic purposes. That figure rose from 0.2% to 0.37% –– almost double, but still lower than half a percent. “It was promising to see that people are sticking to the guidelines and FDA recommendations,” Rezaie said.

The use of GLP1-RA drugs was disproportionately lower in men. Rates of obesity and diabetes are higher among Black and Hispanic patients, but they have lower rates of use, according to the study. That suggests federal or state guidelines could raise awareness because those patients will benefit from the medications, Rezaie said.

The study was intended to show that use of the prescriptions is changing. Based on the result, there is a need for planning so physicians, pharmacists, pharmaceutical makers and the health care field at large avoid the problems of planning, shortages and price spikes that have occurred with even fundamental treatments such as insulin and epinephrine injunctions, Rezaie said.

“These medications are here to stay,” he explained. “But the prescription uses are changing, and we need to plan for it so we don’t get into trouble. We need to get ahead of this because their use is going to increase, and it’s not going to stop. That’s one of the main goals here.”

Side effects

Once a physician determines that the patient is a candidate, there will be more questions.

“It’s a combination of efficacy and side effects,” Herring said. “It’s like, OK, what [are] my [hemoglobin] A1c [and] my weight going to do? And how am I going to feel physically?”

Regarding efficacy, not every patient will react the same way, said Caroline Apovian, M.D., FACP, FTOS, DABOM, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School. Nonresponders typically lose less than 5% of their body weight; super-responders could lose 30%. But doctors don’t have predictors about how patients will respond, Apovian said.

In the Medical Economics poll, a majority, 67%, said significant side effects were rare for their patients, but 32% of respondents said their patients often experienced significant side effects. There has been a lot of public attention on potential catastrophic side effects, but the doctors agreed those are relatively rare.

Long-term effects remain a concern for GLP-1 RAs or any drugs, said Lou Haenel, D.O., a specialist in endocrinology and diabetes with Roper St. Francis Healthcare in South Carolina. The antiobesity drugs still have a package warning about medullary thyroid cancer, which causes fear in patients and, to some extent, providers. The warning is based on test results in rodents.

“But the good news with this is that this is not really translated, in a happy way, into human concerns, based on 20 years of retrospective studies,” Haenel said. “That smoke signal continues to be thought about, and we continue to be mindful of it, but medullary thyroid cancer in humans is actually quite rare, and that was part of the consideration and the concern of using molecules such as this long-term.”

Much more common is gastrointestinal upset as patients adjust to the medicines: nausea, heartburn, vomiting, diarrhea and constipation. Physicians must be open and honest up front and tell patients that in the first few weeks or months of using the drugs, they may not feel very good, said Kristina Henderson Lewis, M.D., M.P.H., SM, an associate professor of epidemiology and prevention at Wake Forest University School of Medicine.

If physicians don’t mention that possibility, and if patients go home and feel terrible, they could stop taking the medicines –– and maybe stop going to the doctor, she said.

“There’s also an opportunity here to help people understand that there are changes they can make to the way that they’re eating when they’re first starting these medications that can actually make them a lot more tolerable,” Lewis said. The advice can be as simple as not going out to eat too often and preparing foods at home that are not super spicy, creamy or fatty.

Herring added more good advice to patients: Stop eating when you feel full.

“If you are listening to your body, you will lose weight on these drugs,” she said.

In the Medical Economics poll, 81% of respondents said the drugs were very effective or somewhat effective in achieving weight loss goals for patients.

Going beyond the new medicines

For the drugs to be fully effective, the physicians agreed patients must know that they need more than a prescription and advice on soothing nausea. They said the drugs are a beneficial treatment but not a cure for obesity. GLP-1 RAs work best when patients receive education and have a plan to make longer-term diet and lifestyle changes.

“People who come in wanting these medications, who have the expectation that you just take your shot once a week and that’s all you have to do [and that] you’re going to lose weight and keep it off forever
–– that’s not going to work,” Apovian said.

If a primary care doctor does not feel comfortable with dietary counseling, referring patients to a registered dietitian for counseling and evaluation of their diet or suggesting online commercially available lifestyle programs is always helpful, Lewis said.

Likewise, with exercise programs, the physicians said commercially available apps and online programs can be helpful, and resistance training, strength training and other exercises can help patients maintain lean muscle mass while possibly strengthening their cardiovascular health, depending on the activity.

Exercise is an important consideration. Shrinking BMI includes losing mass in muscles and bones. That can be problematic for older patients, and physicians should be aware of it.

Yet the physicians agreed that as the patient’s body mass goes down, body mobility often improves, so exercise becomes easier, and some patients become excited to develop new abilities.

Haenel described an example of a patient who is reluctant to go to the gym due to knee pain, hip pain and shortness of breath. Losing 40 pounds due to medication can make it much easier to get in a workout.

“Now they can do things more, they’re more incentivized and motivated, they’re seeing improvements on the scale, they’re seeing better durability in their ability to exercise,” Haenel said. “A lot of times we use the terminology that it’s giving you a jump start to move you in the right direction.”

Patients need to learn and relearn other lessons about good health: Don’t smoke, avoid stress and get a good night’s sleep, among others, Haenel said.

But creating an in-depth treatment plan is part of the challenge for primary care physicians.

“Primary care providers are extremely busy,” Apovian said. “They see patients, and there’s usually not enough time for primary care providers to really educate [them] about lifestyle and then educate about the new medications and, quite frankly, to go through the insurance prior authorizations and coverage issues that are coming out of this explosion in these new medications.”

Paying the cost to see the loss

The doctors agreed they and their peers want patient health to be paramount in discussing medical treatments for patients. But cost is a concern, and the GLP-1 RAs are costly. As of fall 2024, Wegovy’s list price was $1,349 for a month’s supply. Zepbound was $1,059.87 per fill, or four pens for four weeks.

Meanwhile, news reports indicate the drugs are available much more cheaply in other nations. Last year, the GLP-1 RA prices –– and Americans’ health needs –– spurred a hearing of the U.S. Senate Committee on Health, Education, Labor and Pensions. “Stop ripping us off,” Sen. Bernie Sanders, I-Vt., said to Novo Nordisk President and CEO Lars Fruergaard Jørgensen.

Insurance coverage may be good for patients diagnosed with diabetes, but coverage is much more limited –– if it exists –– for patients with obesity or who are overweight with a weight-related comorbidity. Patients see these developments.

In the Medical Economics poll, doctors were split on whether GLP-1 RA drugs were cost-effective –– 42% said yes, 42% said no, and 16% were uncertain. Counting on help from insurance companies is probably not an option: 97% of respondents said patients frequently faced insurance coverage challenges when obtaining the medications.

“I would say, unfortunately, in this country, it comes down to [whether you] can afford it. Do you have insurance coverage for it? Do you have access [to] it?” Kushner said. “As a health care provider, that’s the last thing I want to talk about. But unfortunately, it’s really the bottom line: Can you get it? Can you afford it? And is it covered?”

Now and in the future

No one knows what the future holds, although the physicians offered advice on working with patients now and forecasts on what could happen in 2025 and beyond.

The existing drugs that are injectables could become oral formulations.

“We can anticipate in a very short period of time [that] there will be highly effective medications that mimic what we give by injection, but … given orally as a daily tablet,” Kushner said. That will bring down the cost while potentially increasing the generalizability of the medications, he pointed out.

The pharmaceutical companies have announced plans to increase production capacity, and production will come online eventually. More formulations and production will increase supply, which should drive down prices.

“The cost clearly has to come down,” Kushner said.

Expect new drugs to come to market.

The FDA has approved Zepbound (tirzepatide) for antiobesity. It is the first medication to reduce appetite and food intake through bodily response to GLP-1 and glucose-dependent insulinotropic polypeptide (GIP).

Research findings exist from studies done on hormones including GIP, glucagon and amylin. Kushner and Haenel agreed there is potential to develop even more powerful medications with greater beneficial effects on different organ systems.

“There are multiple newer-generation GLP-GIP crossovers in phase four clinical studies right now that are going to make it to the public space,” Haenel said. “There are studies with other molecules that we’re beginning to look at. We’re going to continue to see the evolution of more and more of these molecules that are going to be pharmacologically helpful.”

Dosing could change.

Although weight-loss effectiveness is evident, doctors don’t yet know if they can eventually reduce doses for patients who respond well and integrate needed lifestyle interventions.

“The FDA gives you pretty strict guidelines on how you’re supposed to titrate up these drugs, and we follow those,” Herring said. “But then, what do you do in maintenance? Do you need the whole dose? Do you have to take 2.4 milligrams of Wegovy every week, or could you scale it back at some point? Could you take it once every two weeks, once a month, and still have those benefits?”

There have been reports of patients losing weight with the drugs, sometimes over months or years, with plans to stop using them and rely on lifestyle changes to maintain a lower weight. Whether those measures would be sufficient or patients would regain weight was unclear.

Consider older, cheaper medications.

Patients and physicians may get excited about the latest breakthroughs and forget that other, older antiobesity medications could be good, affordable options for patients, Lewis said.

Phentermine-topiramate extended-release capsules have good long-term efficacy and safety evidence. Naltrexone-bupropion extended-release tablets could also be more affordable, although the average amount of weight loss seen with this medicine tends to be slightly lower. Generic phentermine has FDA approval for short-term use, but some guidelines have indicated support for long-term use by patients who respond well to it.

“Not jumping right to the absolute most expensive option is really important for doctors to think about because for the vast majority of our patients, if we’re saying to you, basically, we want you to have another mortgage payment every month for the next 15 years, that’s not sustainable,” Lewis said.

Treating obesity will grow as a medical specialty.

More doctors will become obesity specialists. Apovian said that fellowship programs are already increasing, but many more are needed, and training doctors will take time.

In the meantime, primary care physicians will fill the need for obesity care, at least partly. Not only will this change patient health, but it will also change primary care and American health care at large. Traditionally, primary care doctors have focused on treating complications of obesity –– hypertension, elevated lipids, prediabetes and type 2 diabetes, heart disease and more, Apovian said.

“We are now educating primary care physicians and other specialists that treating the obesity is going to eventually mitigate all … the other comorbidities, and so it’s very important to treat the obesity first and then deal with the other complications,” Apovian said. “In that way, eventually we will reduce the health care dollars spent in the United States on heart disease and diabetes and even certain cancers.”