Few prescription drugs have suddenly entered the public consciousness like Ozempic and Wegovy in recent years. Novo Nordisk brand drugs have become as synonymous with weight loss as Viagra and Cialis with erectile dysfunction. But while 2023 made it clear that these and similar drugs are indeed the future of obesity treatment, it also showed that this future looks very messy at times for reasons that have nothing to do with the drugs themselves.
Semaglutide: The Real Deal
Semaglutide is the active ingredient in both Ozempic and Wegovy, which is taken by weekly subcutaneous injection. It is a synthetic and longer-lasting version of the hormone GLP-1a hormone that regulates hunger and metabolic functions such as insulin production. Ozempic was approved by the Food and Drug Administration to treat type 2 diabetes in 2017; in 2021, higher dose Wegovy was approved for obesity.
Wegovy demonstrated unprecedented success in clinical trials that led to its FDA approval, helping people lose 15% of their baseline weight on average. Those results have many experts predicting a new era of obesity medicine. And with the data collected since then, semaglutide just isn’t works as expected but appears to offer benefits that go beyond weight loss, such as alleviating some addiction symptoms.
In November, researchers published a case series of people with alcohol use disorder who began to crave less drinking when they started taking semaglutide for obesity. Some teams are currently conducting drug trials for alcohol dependence and other conditions associated with compulsive behavior, such as binge eating disorder. Elsewhere, scientists have begun studying whether GLP-1 can reduce brain inflammation and slow the progression of diseases such as Alzheimer’s, with some promising early results.
There may be other health benefits. This summer, Novo Nordisk released the results of the SELECT trial, which looked at heart-related outcomes in obese or overweight people with pre-existing cardiovascular disease given high-dose semaglutide or a placebo. Compared to placebo, those on the drug had a 20% lower risk of major (and potentially fatal) cardiovascular problems such as heart attack or stroke for up to five years. In October, the company decided to end a similar trial of semaglutide for chronic kidney disease early, after initial results showed a clear benefit.
This risk reduction is likely largely due to weight loss, which is itself an important finding. Many studies have indicated that weight loss can improve the overall health of obese people, but this is difficult to directly prove in part because people generally struggle to lose and maintain a large body weight. amount of weight long enough to study them, outside of interventions like surgery. . But there is some research suggested that these benefits are not produced from weight loss alone and may involve other effects of semaglutide on the body.
Not all of these research methods are necessarily paid. But even if only a few do, these drugs could improve and potentially save the lives of millions more people than anyone originally envisioned.
A Competitor Enters the Ring: Tirzepatide
Perhaps the most important development that occurred this year was the FDAs approval of Eli Lillys Zepbound for obesity in November. The drugs’ active ingredient is tirzepatide, which mimics GLP-1 and another combination of the GLP hormone associated with hunger that seems to be more effective in treating obesity than Wegovy. In clinical trials, people taking tirzepatide lost 20% to 25% of their baseline weight on average, a level of weight loss approaching the results seen in the most successful bariatric surgeries.
The arrival of Zepbounds not only reinforces a fierce competition for the obesity drug market in the future, it indicates that these products are just the beginning. There are now dozens other obesity drug candidates in the pipeline, some of these may help people lose more weight than either semaglutide or tirzepatide, or may offer other advantages such as being easier to take through a pill rather than as an injection.
No Free Lunch: Effects of Weight Loss Drugs
As miraculous as these drugs seem, few medical treatments are without risk. People who take them often experience gastrointestinal issues such as vomiting and diarrhea. These symptoms tend to lessen over time and are usually not severe enough for most people to stop taking treatment. But there is also some indication that people can develop serious complications such as gastroparesis (paralysis of the stomach), pancreatitis, and even suicidal ideation. In September, the FDA updated its labeling of Wegovy and Ozempic, warning that the products could cause ileus (intestinal blockage) based on adverse event reporting data, though the agency stopped short of confirming it as a known danger.
Some of these suspected side effects, such as suicide, have little evidence currently support one link to GLP-1 use more than others. And in general, serious problems like stomach paralysis and ileus appear to be rare. But doctors and patients need to remain aware of these issues and evaluate whether the benefits are worth potentially facing these risks.
Semaglutide Off-Label and on the Black Market
Not all complications surrounding these drugs are medical. Production problems and unexpected demand led to continued shortages of both Wegovy and Ozempic, as many doctors began prescribing the latter drug off-label for weight loss. This in turn has affected the care of people taking Ozempic as intended, with diabetes patients transferred in others, possibly less effective drugs.
Inconsistent supply, high list prices (over $1,000 a month without coverage), and the regular lack of insurance coverage of these drugs have also helped fuel the emergence of a gray and black market. People are now buying custom-made, cheaper semaglutide from compounding pharmacies, though there is no guarantee of its safety or effectiveness. And the increasing popularity of compounded semaglutide may contribute to the increase in overdoses. Earlier this month, the Americas Poison Centers reported that about 3,000 drug-related calls were made to poison control centers nationwide this year, a 15-fold increase from calls in 2019. In other countries, including Austria, fake semaglutide has begun to spread, and some people have ended up in the hospital from taking mislabeled products that actually contain insulin.
The Road Ahead
The most recent clinical data suggest that many people do regain some of their lost weight if they stop taking these drugs. That’s not an inherent problem, as many chronic conditions require ongoing treatment, but it complicates things. Will people be able to continue to pay for these drugs, for example, especially as insurance companies begin to tighten their coverage of them? What will happen to the health of people who lose and regain weight as a result of losing coverage, since weight cycling is generally thought to be harmful?
Barring the discovery of a dangerous and relatively common side effect, it is unlikely that these drugs will become more popular anytime soon. But even in a world where these drugs remain generally safe and effective, not everyone will be a fan of them.
There are some critics argued that these drugs do little to help most obese people and perpetuate harmful messages about obesity, such as the idea that people must be thin to be healthy. Conversely, you don’t have to scroll too far through social media posts about drugs to find people dismissing them as a quick fix and saying that people should lose weight the real way, through lifestyle changes alone that if people don’t spend billions of dollars annually there is no point in trying to do that.
Others make a more nuanced argument, that these drugs do not address the drivers of obesity, such as barriers to access to nutritious, fresh food. But then, neither are statins for cardiovascular disease or chemotherapy for colon cancer treatments for other chronic conditions that are also linked to a less healthy diet or lack of exercise.
It’s true that drugs like semaglutide and tirzepatide won’t solve obesity by themselves (assuming you believe it’s something that can be solved). But they have and will continue to help some people lose weight and possibly be healthier in general as long as you can afford the cost or find a safe supply in the first place. Predicting anything beyond this, including its impact on society at large, is not so easy.
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