Wegovy and Other New Weight Loss Drugs Actually Work—so What’s Next?

Few prescription drugs have entered the public consciousness as abruptly as Ozempic and Wegovy have in recent years. Novo Nordisk’s brand-name medications have become as synonymous with weight loss as Viagra and Cialis are with erectile dysfunction. But while 2023 has made it clear that these and similar drugs really are the future of obesity treatment, it’s also shown that this future looks plenty messy—sometimes for reasons that have little to do with the drugs themselves.

Semaglutide: The Real Deal

Semaglutide is the active ingredient in both Ozempic and Wegovy, which are taken via a weekly subcutaneous injection. It’s a synthetic and longer-lasting version of the hormone GLP-1—a hormone that regulates hunger and metabolic functions like insulin production. Ozempic was approved by the Food and Drug Administration to treat type 2 diabetes in 2017; in 2021, the higher-dose Wegovy was approved for obesity.

Wegovy demonstrated unprecedented success in the clinical trials that led to its FDA approval, helping people to lose 15% of their baseline weight on average. Those results had many experts predicting a new era of obesity medicine. And in the data collected since, semaglutide is not only working as expected but appears to offer advantages that extend beyond weight loss, such as mitigating some symptoms of addiction.

In November, researchers published a case series of people with alcohol use disorder who began to crave drinking less once they started taking semaglutide for obesity. Several teams are now currently conducting trials of the drug for alcohol dependence and other conditions linked to compulsive behaviors, such as binge eating disorder. Elsewhere, scientists have begun studying whether GLP-1s can reduce brain inflammation and slow down the progression of disorders like 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 the heart-related outcomes of obese or overweight people with pre-existing cardiovascular disease who were 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 preliminary results found a clear benefit.

This reduction in risk is likely largely due to weight loss, which is itself an important finding. Many studies have indicated that losing weight can improve the overall health of people with obesity, but it’s been difficult to directly prove—in part because people generally struggle to lose and keep a substantial amount of weight off long enough to study them, outside of interventions like surgery. But some research has suggested that these benefits aren’t produced from weight loss alone and may have to do with other effects of semaglutide on the body.

Not all of these research avenues will necessarily pay off. But even if only some do, these drugs could improve and potentially save the lives of millions more people than anyone originally foresaw.

A Competitor Enters the Ring: Tirzepatide

Perhaps the most important development that occurred this year was the FDA’s approval of Eli Lilly’s Zepbound for obesity in November. The drug’s active ingredient is tirzepatide, which mimics both GLP-1 and another hunger-related hormone GIP—a combination that seems to be even more potent at treating obesity than Wegovy. In clinical trials, people taking tirzepatide have lost 20% to 25% of their baseline weight on average, a level of weight loss approaching the results seen with the most successful bariatric surgeries.

Zepbound’s arrival not only cements a fierce competition for the obesity drug market ahead, it suggests that these products are just the beginning. There are now dozens of other obesity drug candidates in the pipeline, some of which might help people lose more weight than either semaglutide or tirzepatide, or could offer other advantages such as being easier to take via a pill rather than as an injection.

No Free Lunch: Weight Loss Drug Side Effects

As near-miraculous as these drugs might seem, few medical treatments come risk-free. People taking them will often experience gastrointestinal issues like vomiting and diarrhea. These symptoms tend to wane away over time and usually aren’t awful enough for most people to stop taking the treatment. But there’s also been some indication that people can develop serious complications like gastroparesis (stomach paralysis), pancreatitis, and even suicide ideation. In September, the FDA updated its labeling of Wegovy and Ozempic, warning that the products could potentially cause ileus (intestinal blockage) based on adverse event reporting data, though the agency stopped short of confirming it as a known risk.

Some of these suspected side-effects, like suicide ideation, have less evidence currently supporting a link to GLP-1 use than others. And in general, severe problems like stomach paralysis and ileus appear to be rare. But doctors and patients will have to stay aware of these issues and evaluate whether the benefits are worth possibly encountering these risks.

Semaglutide Off-Label and on the Black Market

Not every complication surrounding these drugs is medical. Production problems and unexpected demand have led to constant shortages of both Wegovy and Ozempic, as many doctors have started to prescribe the latter drug off-label for weight loss. This in turn has affected the care of people taking Ozempic as intended, with diabetes patients being switched to other, possibly less effective drugs.

The outmatched supply, high list prices (over $1,000 a month without coverage), and routine lack of insurance coverage of these drugs has also helped fuel the emergence of a gray and black market. People are now buying custom-made and much cheaper semaglutide from compounding pharmacies, though with no guarantee of its safety or effectiveness. And the rising popularity of compounded semaglutide may be contributing to an increase in overdoses. Earlier this month, America’s Poison Centers reported that around 3,000 calls linked to the drug have been made to poison control centers nationwide this year so far—a 15-fold increase from calls made in 2019. In other countries, including Austria, counterfeit semaglutide has started to circulate, and some people have already landed in the hospital from taking falsely labeled products that actually contain insulin.

The Road Ahead

The latest clinical data suggests that many people will regain some of their lost weight if they stop taking these drugs. That isn’t inherently a problem, as many chronic conditions require ongoing treatment, but it does complicate things. Will people be able to keep paying for these drugs, for instance, especially as insurance companies have started to become more restrictive in their coverage of them? What happens to the health of people who lose and regain weight as a result of losing coverage, since weight cycling in general is thought to be harmful?

Barring the discovery of a dangerous and relatively common side effect, it’s unlikely that these drugs will be getting less popular anytime soon. But even in a world where these medications remain generally safe and effective, not everyone is going to be a fan of them.

Some critics have argued that these drugs do little to actually help most fat people and perpetuate harmful messages about fatness, such as the idea that people must be thin to be healthy. Conversely, you don’t have to scroll too far on social media posts about the drugs to find folks dismissing them as a quick fix and saying people should lose weight the “real way,” through lifestyle changes alone—as if people haven’t been spending billions of dollars annually in vain trying to do that.

Others make a more nuanced argument, that these drugs don’t address the drivers of obesity, such as the barriers in access to nutritious, fresh foods. But then, neither do statins for cardiovascular disease or chemotherapy for colon cancer—treatments for other chronic conditions that are also linked to a less healthy diet or a lack of exercise.

It is true that drugs like semaglutide and tirzepatide won’t solve obesity on their own (assuming you believe it’s something to be solved). But they are and will continue to help some people lose weight and possibly become more healthy overall—so long as you can afford the cost or find a safe supply in the first place. Predicting anything beyond that, including their impact on society at large, isn’t so easy.

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