December 9, 2023

As an obesity and lipid specialist physician, I’ve seen how drugs like Ozempic, Wegovy, and their predecessors have completely changed the landscape for people struggling with type-2 diabetes and obesity. Meanwhile, people still don’t really understand how they work and there are major misconceptions about them floating around, particularly on social media. What I know is that the current drugs on the market are only the start—more options are coming soon, and they may be even more effective.

One that’s already being prescribed is Mounjaro, though at this stage, it’s only technically FDA-approved to treat type-2 diabetes, like Ozempic. In summer 2023, it’s likely that Mounjaro (known as tirzepatide generically) will be officially approved by the FDA for weight loss as well (it seems to be one more large study on safety and efficacy away).

Mounjaro, much like Ozempic, is currently being prescribed off label for the treatment of obesity, particularly given the recent shortages of Wegovy, which is FDA-approved for obesity. Wegovy and Ozempic are the same drug, semaglutide—they’re just different doses. Wegovy has been shown to help people lose 15 percent of their body weight. At certain doses, Mounjaro may be able to induce a loss of 21 percent of body weight. These results are quickly approaching what bariatric surgery can do.

 

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The reason Mounjaro is more powerful may lie in the fact that it employs more weight loss mechanisms than Wegovy. Ozempic and Wegovy belong to a class of drugs called glucagon-like peptide-1 (GLP-1) agonists. GLP-1 is naturally produced in the intestines and sends satiety signals to the brain. These medications induce weight loss because they act like GLP-1 in the body and are able to suppress appetite (“agonist” refers to a drug that binds to a receptor inside a cell or on its surface and causes the same action as the substance that normally binds to the receptor). These meds also help spur the pancreas to produce insulin, which can help lower blood sugar for those with diabetes.

Mounjaro, on the other hand, is a GLP-1/GIP agonist, meaning that in addition to acting as GLP-1 in the body, it also mimics the glucose-dependent insulinotropic polypeptide (GIP), sometimes known as the gastric inhibitory polypeptide, that, like GLP-1, triggers insulin secretion. While there’s debate about how it works, the addition of GIP in this case may be increasing the effectiveness of GLP-1, creating an added weight loss effect.

The future of obesity medicine is all about developing compounds or combining compounds that hit multiple receptors in the body related to appetite and potentially even metabolic rate, nutrient partitioning (how your body selects which fuels it puts in storage), and lean muscle mass retention. There are many new compounds in the pipeline that are currently being researched, with the goal that each new compound can produce a greater percentage of weight loss with fewer side effects. Therapies that do not need to be taken as frequently are also in the works.

CagriSema (a combination of cagrilintide and semaglutide) looks very promising. Cagrilintide emulates amylin, a hormone from the pancreas that also has an effect on satiety.

Another is retatutride, which is a GLP-1/GIP/glucagon agonist. This compound is similar to tirzepatide, but goes a step further by adding on glucagon agonism. It’s possible the added glucagon agonism helps with energy expenditure, allowing people to burn more calories, on top of the appetite suppression.

In addition to the new compounds being researched, there are ongoing studies looking at how higher doses of the current GLP-1 agonists are tolerated. And while most of these compounds start off being tested and approved for type-2 diabetes, and later are tested and approved specifically for obesity, that order may be changing. A compound called AMG-133, a GLP-1 agonist with an antibody that, in contrast to tirzepatide, inhibits GIP instead of increasing it, looks like it’s being studied first for obesity.

It might seem like it, but these medications didn’t come out of nowhere. Ozempic, Wegovy, and Mounjaro are the result of decades of research and development. Since the first GLP-1 agonist was approved in 2005, a succession of new compounds has hit the market every few years. First there was exenatide (Byetta), then liraglutide (Saxenda and Victoza), then dulaglutide (Trulicity), then semaglutide (Ozempic and Wegovy), and then tirzepatide (Mounjaro).

Before the next generation of drugs arrives, it’s critical to set the record straight: This isn’t just an out-of-control pharmaceutical-industry fueled weight-loss fad. Let me bust some of the many myths surrounding these newly-in-the-zeitgeist-but-not-new medicines.

Myth 1: People shouldn’t be using drugs like Ozempic and Mounjaro for weight loss alone.

Obesity is a chronic disease. It has been classified as such since the 1990s, owing to the fact that the body fights back when people try to lose weight, and because excess weight is associated with an increased risk for a host of health issues, including type-2 diabetes, cardiovascular events, Covid-19 complications and more.

Yet for decades, our society has shamed people with obesity. It’s told them their weight is simply a reflection of their failure to eat healthy foods and exercise. This is largely due to the weight stigma that permeates every aspect of our culture, from TV shows to healthcare.

“People who use these medications still have to make healthy lifestyle choices and work hard to lose weight. But they can do it without starting at a disadvantage.”

Weight stigma hurts people with bigger bodies in many ways. Research shows that people who are classified as having obesity are more likely to be discriminated against at work and dismissed in healthcare settings. But another way weight stigma hurts those with bigger bodies is that there is also judgement attached to getting medical treatment for obesity—whether that’s bariatric surgery or now, using an FDA-approved weight loss drug. It’s seen as a “crutch” or “the easy way out,” when that couldn’t be further from the truth. Just like you wouldn’t tell a person with type-2 diabetes that they should feel bad for injecting insulin, you shouldn’t tell people with obesity they should feel bad for using medications to treat their obesity.

It’s true that most of the GLP-1 agonists on the market are approved as type-2 diabetes drugs, and not all of them are approved for obesity yet—but it’s a major misconception that people shouldn’t be taking them for weight loss alone. Given that semaglutide was FDA-approved specifically for obesity treatment (in its Wegovy form) in 2021, we know that Ozempic (the same compound) is safe and works for weight loss.

In the face of Wegovy shortages, people can work with their doctor to see if an off-label prescription is appropriate for them. Obesity should be taken as seriously as any other disease, and people struggling with it have just as much of a right as anyone else to medication that can help them manage it.

Myth 2: You can take these drugs to lose weight, then get off them.

Another big misunderstanding about these drugs is that they are a “quick fix,” that you can use them to lose weight and then stop taking them. In truth, they only work if you consistently take them, similar to a blood pressure medicine or other chronic disease medicines. They’re meant to be taken indefinitely, and going on and off these drugs may cause a yo-yo effect on appetite and weight. There may be some folks who can wean themselves off these medications, but many will need to stay on at least a low dose.

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By influencing one of the keys to long-term weight loss—appetite regulation—these medications allow people to live the lifestyle they already know they need to in order to lose weight. Most people know that eating an apple instead of chips is probably a good idea if they’re trying to lose weight. But why can’t they do it despite the knowledge? It’s because the brain is powerful in nudging people to eat bigger portions and high-calorie foods, particularly for those with a genetic predisposition for obesity. Some people are able to practice moderation with these foods. Some people can abstain. Many cannot, despite their best efforts.

When people who struggle with obesity—despite the best available coaching and advice—try these medicines, they describe feeling what it must be like to not struggle with appetite and weight. They say they feel “normal.” They still have to make healthy lifestyle choices and work hard to lose weight. But they can do it without starting at a disadvantage.

“It’s a fact that diet and exercise only work for a minority of obesity patients who want to lose weight. With these new tools, there’s now another option.”

Obesity medication could go far to improve the lives of people with health concerns related to obesity—but only if we let it. Currently, only 30 percent of insurers will cover these medications, another way weight stigma and the misconception that obesity is purely a lifestyle issue continues to harm people.

Myth 3: These medications are great whether you’re trying to lose 15 pounds or 100 pounds.

People without a type-2 diabetes or obesity diagnosis shouldn’t seek these medications out. Not only does that aggravate supply issues for people with true medical conditions who depend on these drugs, there are risks. Someone who is looking to lose a few pounds may become underweight and lose bone and muscle mass instead of excess fat if they take them. While the drugs are relatively safe, there is potential for uncomfortable side effects—mainly nausea.

Using these medications requires the oversight of a qualified physician. I wouldn’t trust a doctor who is helping you access a drug you don’t really need, especially if they’re prescribing a version from a compounding pharmacy (one that not only distributes drugs but makes them, which introduces risk of contamination).

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It’s a fact that diet and exercise only work for a minority of obesity patients who want to lose weight, because they’re incredibly difficult to stick with. With these new tools, there’s now another option—a relatively safe, noninvasive, effective one—for helping people lose weight and keep it off without a constant battle.

At the end of the day, everyone should have full autonomy over their own body. Someone who is classified as having obesity, but is otherwise healthy and happy shouldn’t feel pressure to lose weight or be discriminated against for their size, ever. At the same time, those who are suffering and who do need a change shouldn’t feel shame or experience barriers to access to tools that can help.


Spencer Nadolsky, DO, is a board-certified obesity and lipid specialist physician. He is the medical director of JoinSequence.com, where he helps deliver accessible comprehensive obesity treatment online. You can follow him on Instagram at @drnadolsky.


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