Carlene Johnson, a 48-year-old Boston resident, couldn’t remember a time when she didn’t feel hungry. Even after eating a full meal, she felt like she needed to eat again just minutes later. She tried many diets and programs, but the hunger always lingered. All the while, she felt the constant pressure and stigma from society for having a bigger body.
In January 2021, her doctor recommended weekly injections of liraglutide, a medicine that can help people lose 5% to 10% of their body weight when combined with diet and exercise. Johnson’s results were even better. Over four months on the medication, her weight decreased from 210.4 pounds to 181.8, a loss of 28.6 pounds, or 13.6% of her peak weight.
The medication liberated her from constant hunger. For the first time, she had a true understanding that what she was experiencing couldn’t be solved through keto or kickboxing. “It wasn’t until I had this physical intervention that I realized the degree to which my biochemistry is abnormal,” Johnson said. “Finally, I could eat and actually feel full.”
Liraglutide, prescribed as Saxenda, is a GLP-1 receptor agonist, a class of drugs used to treat type 2 diabetes but now often marketed for weight loss — even for those without diabetes, like Johnson. Saxenda was approved in 2014. A newer drug of this class is semaglutide (sold under the brand name Wegovy), which was approved in 2021 and was found, on average, to reduce weight by 15% in one clinical trial where people took the drug for 68 weeks.
And now, a related drug called tirzepatide may be even more promising. It’s the first to activate receptors for both GLP-1 and a second molecule called GIP.
Tirzepatide, approved in May for people with type 2 diabetes, is marketed under the name Mounjaro. A clinical trial published last month (called SURMOUNT-1) found many people taking tirzepatide for obesity lost a jaw-dropping 20% of their weight or even more. By comparison, bariatric surgery results in 25% to 30% weight loss over a one- to two-year period.
Before tirzepatide can be made available for weight loss, the manufacturer Lilly currently has to go through three more trials, but it is seeking a fast track.
“We are engaging with the FDA to potentially discuss an expedited path forward based upon the results we saw in SURMOUNT-1. We are hoping to have an update on that conversation with the FDA before the end of this year,” said Maggie Pfieffer, a spokesperson for Lilly's diabetes program.
Dr. Sean Wharton, an internal medicine physician in Toronto, was one of the contributing authors on SURMOUNT-1. He believes that once tirzepatide is available commercially for weight loss, it has the potential to change the game and become a blockbuster drug or household name.
“I think that semaglutide opened the door in a significant way. It got people talking about it. It got people understanding it,” he said. “And now, the tirzepatide molecule will really bust open those same doors, and newer and better molecules will hopefully follow this one.”
However, there are important things to know about all of these medications. They can be expensive and have serious side effects. Plus, sometimes they aren’t covered by insurance, and they don’t always work for everyone. When they do work, it’s often because they are combined with diet and exercise.
And it’s not clear if there’s an end in sight for people taking the drug, who may regain the weight after stopping the medication. As is the case with most chronic conditions, some experts believe people with health issues related to their weight will require care, management, and possibly a prescription indefinitely.
How do these drugs work?
The two molecules, GLP (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide or gastric inhibitory polypeptide), are incretins, or hormones that are released by the intestine when you eat; they stimulate insulin release, lower blood sugar, and send a signal to the body that you are full. These medications, which mimic the hormones, can enhance insulin release, resulting in a slower digestive process and reduced appetite, thereby encouraging weight loss.
“These molecules stop hunger in the face of dietary intervention,” Wharton said.
Of course, there’s no such thing as a magic pill, nor is there a magic injection, for weight loss. For people taking these medicines, modifications to diet and physical activity are a must.
Many have also reported rough gastrointestinal side effects. About 80% of participants in tirzepatide’s clinical trial reported a side effect, most often nausea, diarrhea, and constipation, and 4% to 7% of people had to stop taking it due to side effects, compared with about 3% of people taking a placebo. (There’s an entire subreddit where people taking semaglutide share colorful war stories, advice, and encouragement.)
These drugs have also been linked to a risk of thyroid cancer in animal studies, but that has not been proven to be a risk in humans. (People with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 shouldn't take these medications.)
GLP-1 agonists also have a risk of causing other rare but dangerous side effects, like pancreatitis and gallbladder disease. Those are listed in the prescribing information, but some studies have shown a higher risk with GLP-1 agonists and others have not.
They don’t work for everyone
Some people taking GLP-1 agonists for weight loss experience lackluster results, and no one knows exactly why. In the tirzepatide trial, in which about half of participants lost 20% or more of their body weight on the higher doses of the drug (compared to the placebo group, where only 3% lost 20% or more of their body weight), about 9% of people lost less than 5%.
Wharton said explaining this disparity should be a priority for future research.
“Unfortunately in weight management, there’s a significant amount of variability in the response to medication,” he said. “But that’s what we need to address in the future. The person who failed, how can we make that person’s life better?”
Either way, the medications need to be combined with diet and exercise to be most effective.
Dr. Cindy Duke, a reproductive endocrinology and infertility specialist based in Las Vegas, prescribes semaglutide for some of her patients, many of whom are planning to eventually become pregnant. She recommends they engage in meaningful lifestyle modifications, including educating themselves on healthy carbs, proper protein ratios, and how to exercise.
“I don’t need them to be a gym rat, but I need them to increase their lifestyle from being less sedentary,” Duke said.
The medications can be expensive and sometimes in short supply
The retail price for liraglutide (Saxenda) and semaglutide (Wegovy) injector pens is around $1,700 per month for uninsured patients in the United States. That’s a little over $20,000 per year.
The type 2 diabetes formulations of these medications also have high price tags, though they are significantly lower. The retail price for Ozempic (the version of semaglutide for people with type 2 diabetes) and Mounjaro (the brand name for tirzepatide) is about $1,100, or about $600 less per month.
With Johnson’s insurance, her copayments have been $50 per month. She covers half of this with a savings card provided by the manufacturer.
“I’m incredibly fortunate to have good insurance as well as the finances to cover the higher co-pay if I needed to do so,” she said.
Some insurance companies won’t cover some GLP-1 agonists. For example, Medicare and most insurance companies won’t cover Wegovy, according to GoodRx. An app called Calibrate offers personalized coaching and access to physician-prescribed GLP-1 agonists for $1,649 per year or $138 per month. That is in addition to the cost of medications, but on its website, Calibrate claims to work with users’ insurance companies to get them covered. It also guarantees weight loss of 10% or more. (Calibrate did not respond to a request to comment by the time of publication.)
Irrespective of the cost, new prescriptions of Wegovy have been temporarily halted. Novo Nordisk, the manufacturer of both Wegovy and Ozempic, has had to shift its production schedule in the face of its third-party vendor’s shortage of needle pens used to deliver the medicine. In order to continue serving patients who are already taking Wegovy, Novo Nordisk is currently only producing the two highest doses, 1.7mg and 2.4mg, and the company has said it hopes to be able to fulfill the increasing demand for Wegovy by the second half of 2022.
Because of the Wegovy shortage, and because Ozempic is priced much lower, some patients have sought off-label prescriptions of the type 2 diabetes medicine from their doctors. However, Dr. Jason Brett, Novo Nordisk’s executive director of medical affairs for diabetes and obesity, is insistent that healthcare providers should not be prescribing the medications interchangeably.
“The active pharmaceutical ingredient is the same, semaglutide, but they have different doses, they have different dose escalation schedules, and they have different devices,” he said.
It’s not clear if you need to take them indefinitely to maintain weight loss
When Johnson was taking Saxenda, she was better able to manage her diet without facing constant hunger. But then her weight started to plateau. Even when she was taking the highest dosage of the drug, her appetite returned, so she stopped taking the weekly injection. Soon, she returned to her peak weight.
“After I quit taking it, I stopped doing a lot of the things I should have been doing, like tracking my food and weighing myself regularly. And within a few weeks, I was back to full force,” she said. “If you don’t change your behaviors, then it’s just a short-term fix, right?”
She is trying Wegovy next. However, because of the shortage in low-dose versions of the drug, she may be more likely to experience nausea as a side effect. Her doctor prescribed an anti-nausea medication just in case, and she notes there are “not many options.”
Wharton believes these medicines empower people to make healthy lifestyle changes — but, just as with any other chronic conditions of the mind or body, people experiencing health problems related to obesity will likely always require some form of treatment.
“The drug doesn’t melt fat. All it does is allow you to change your behavior,” Wharton said. “But since we know that this is a chronic medical biological condition, then patients can’t come off the medication ever, just like with any other medication for any other chronic condition.”
Wharton also believes the idea that people can or should be weaned from medication is actually counterintuitive and harmful.
“That’s like telling someone with schizophrenia to just train themselves not to hear the voices,” he said. “But, of course, if you have a patient with schizophrenia and you take them off their medication, what ends up happening? The voices come back.”
Duke has a different perspective. She believes that even though her patients with obesity and/or prediabetes may take liraglutide and semaglutide, this doesn’t necessarily mean they’ll need a lifelong prescription.
“I’m not a proponent of keeping people on medicines they don’t need to be on,” she said. “If someone can maintain their loss because they’ve learned how to manage their diet, how to exercise, how to really help their body reprogram their insulin sensitivity response, I love to see that. I’d like to at least see patients have an opportunity to wane their dose in the future or come off completely.”
When she has someone taking anti-obesity medication who decides they are ready to conceive, Duke tapers their dosage.
“This is important, because they cannot continue this medication during pregnancy,” she said. Wegovy should be discontinued at least two months before a planned pregnancy, for male and female patients alike, due to the risk of fetal harm, according to the prescribing information. For Ozempic, the antidiabetic formulation of the same molecule, the FDA says it should only be used during pregnancy if the potential benefit outweighs the risks, which can include fetal abnormalities and miscarriage. (High blood sugar due to diabetes can also increase the risk of birth defects, stillbirth, and pregnancy complications, and insulin is considered the safest drug to reduce that risk.)
“I had a patient who was taking one of these drugs for the bulk of the pandemic. When they were ready to start a family, we stepped down such that by the time their pregnancy test was positive, they were off the medication.”
They aren’t for those with short-term weight loss goals
If hype around these medications has you wondering if perhaps this new class of drug might be the answer to your short-term plan to lose a few pounds before an upcoming wedding, experts say these drugs are not for you.
Anti-obesity medications are not for those who might be able to modify their behaviors on their own, Wharton said.
“If someone wants to lose 10 pounds, they can do it with behavioral changes. They can exercise more or eat better. If you need to lose 10 pounds, I’m not talking to you,” he said. “But dealing with chronic obesity is a neurological science question, not a behavioral science question like everyone wants it to be.”
In the same way that Johnson’s relief while taking liraglutide provided her with a greater understanding of her constant hunger, GLP-1 treatments are providing the medical community with insight into how obesity works. Wharton hopes the advent of these medications will help to destigmatize chronic obesity among doctors, to clarify that this is a treatable health issue, not a flaw of character.
“The fact that these medications work within the brain, where the disease lives, makes it a lot clearer that there's biology connected to it,” Wharton said. “The more that we believe that this is a biological medical condition — and we get to that understanding because the medications work — the more that we can recognize that it's not this person's fault.”