The future of weight loss drugs like Ozempic, Wegovy, and Mounjaro

As an obesity and lipid profile clinician, I’ve seen how drugs like Ozempic, Wegovy, and their predecessors have completely changed the landscape for people with type 2 diabetes and obesity. Meanwhile, people still don’t really understand how they work and there are huge misconceptions about them, especially on social media. What I do know is that the current medications on the market are only the beginning – more options are coming soon, and they may be even more effective.

One that has already been prescribed is Mounjaro, although at this point it is only technically approved by the FDA to treat type 2 diabetes, as is Ozempic. In the summer of 2023, it’s likely that Mounjaro (generally known as tirzepatide) will be officially approved by the FDA for weight loss, too (it seems like another big safety and efficacy study is out of the way).

Mounjaro, like Ozempic, is currently prescribed off-label for the treatment of obesity, especially given the recent shortage 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 cause a loss of up to 21 percent of body weight. These results quickly approximate what bariatric surgery can do.

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The reason behind Mounjaro’s strength may lie in the fact that it uses more weight loss mechanics than Wegovy. Ozempic and Wegovy belong to a class of medications called glucagon-like peptide-1 (GLP-1) agonists. GLP-1 is produced naturally in the gut and sends satiety signals to the brain. These drugs lead to 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 or on a cell surface and causes the same effect as a substance that would normally bind to the receptor). These medications also help stimulate the pancreas to produce insulin, which can help lower blood sugar for people with diabetes.

Mounjaro, on the other hand, is a GLP-1/GIP agonist, which means that in addition to acting as GLP-1 in the body, it also mimics a gastric inhibitory polypeptide (GIP) that, like GLP-1, triggers insulin secretion. While there is debate about how it works, adding GIP in this case may increase the effectiveness of GLP-1, creating an additional weight loss effect.

The future of obesity medicine is about developing compounds or combining compounds that hit multiple receptors in the body related to appetite and perhaps even metabolic rate, nutrient partitioning (how your body chooses the fuel it stores), and lean muscle mass retention. Several new compounds in research are currently under research, with the goal that each new compound will result in a greater percentage of weight loss with fewer side effects. Treatments that do not need to be taken frequently are also in the works.

CagriSema (a combination of cagrilintide and semaglutide) looks very promising. Cagrilintide mimics 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 it takes it a step further by adding a glucagon agonist. It is possible that the added agonist glucagon could help with energy expenditure, allowing people to burn more calories, in addition to suppressing appetite.

In addition to the new compounds being investigated, there are ongoing studies looking at how higher doses of current GLP-1 agonists can be tolerated. And while most of these compounds start out being tested and approved for type 2 diabetes, and then are tested and approved specifically for obesity, that order may change. A compound called AMG-133, a GLP-1 agonist with an antibody that, unlike tirzepatide, inhibits GIP rather than increasing it, appears to be being studied first for obesity.

It may seem so, but these drugs did not appear out of the blue. Ozempic, Wegovy and Mounjaro are the result of decades of research and development. Since the first GLP-1 agonist was approved in 2005, a series of new compounds have appeared on the market every few years. First there was exenatide (Byetta), then liraglutide (Saxenda and Victoza), then dulaglutide (Trulicity), then semaglutide (Ozempic and Wegovy), 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 fad in the weight-loss drug industry. Let me think of some of the many myths that surround these new zeitgeist-yet-not-so-new drugs.

Myth 1: People shouldn’t use drugs like Ozempic and Mounjaro just for weight loss.

Obesity is a chronic disease. It’s been categorized as such since the 1990s, due to the fact that the body fights back when people try to lose weight, and because excess weight has been linked to an increased risk of a range of health problems, including type 2 diabetes, cardiovascular events, complications from Covid-19 and more.

However, for decades, our society has shamed people who are obese. They are told that their weight is simply a reflection of their failure to eat healthy foods and exercise. This is largely due to the stigma that permeates every aspect of our culture, from TV shows to healthcare.

Weight stigma hurts large people in many ways. Research shows that people classified as obese are more likely to be discriminated against at work and fired in healthcare settings. But another way the weight stigma hurts is that there’s also a provision around getting medical treatment for obesity — whether it’s bariatric surgery or now, using an FDA-approved weight-loss drug. It is seen as a “crutch” or “easy way out”, while that couldn’t be further from the truth. Just as you don’t tell someone with type 2 diabetes that they should feel bad for injecting insulin, you shouldn’t tell obese people that 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 medications for type 2 diabetes, and not all of them are approved to treat obesity yet — but it’s a major misconception that people shouldn’t take them to lose weight on their own. Given that semaglutide was FDA-approved specifically for the treatment of obesity (in the form of Wegovy) in 2021, we know that Ozempic (the same compound) is safe and works for weight loss.

Faced with a Wegovy shortage, people can work with their doctor to see if an over-the-counter medication is right for them. Obesity should be taken as seriously as any other disease, and people who suffer from it have just as much right as anyone else to take medications that can help them deal with it.

Myth 2: You can take these drugs to lose weight and then quit.

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

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

When people struggling with obesity – despite the best guidance and advice available – try these medications, they describe feeling what it must have been 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 so without starting to be at a disadvantage.

Obesity medications can go a long way in improving the lives of people with obesity-related health concerns — but only if we allow it. Right now, only 30 percent of insurance companies will cover these drugs, which is another way of stigmatizing weight, and the misconception that obesity is purely a lifestyle issue continues to hurt people.

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

People who do not have type 2 diabetes or a diagnosis of obesity should not seek these medications. Not only does this exacerbate supply issues for people with real medical conditions who are dependent on these medications, there are risks. A person looking to lose a few pounds may become underweight and lose bone and muscle mass rather than excess fat if they take it. While the medications are relatively safe, there is a potential for uncomfortable side effects—nausea mainly.

The use of these medications requires the supervision of a qualified physician. I don’t trust a doctor to help you get access to medication you don’t really need, especially if he prescribes a compound pharmacy version (not only dispenses medications, but manufactures them, which puts you at risk of contamination).

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It is a fact that diet and exercise only work for a minority of obese patients who want to lose weight, because it is very difficult to stick to. With these new tools, there is now another option—relatively safe, non-invasive, and effective—to help people lose weight and keep it off without a constant battle.

At the end of the day, everyone should have complete autonomy over their own body. A person classified as obese, but otherwise healthy and happy, should not feel pressured to lose weight or experience discrimination because of their size at all. At the same time, people who are struggling and need change should not feel ashamed or face barriers in accessing tools that can help.

Spencer Nadolski, MD, a board-certified obesity and lipid specialist. He is the Medical Director of JoinSequence.com, where he helps provide comprehensive obesity treatment accessible online. You can follow him on Instagram at @drnadolsky.