You’ve likely been hearing a lot about Ozempic (semaglutide, also branded as Wegovy), the hottest new drug being used (and woefully, misused) for weight loss by millions of people, including reality TV stars and other celebrities. It’s a trending topic for social media influencers, too, who make exceptional claims for the drugs, and it has been featured in articles in major magazines, podcasts, and of course nonstop advertising. On TikTok alone, the hashtag #ozempic has had more than 1 billion views.
All this hype may have piqued your curiosity but left you somewhat bewildered. That’s because for decades, weight-loss drugs have provided only limited success in the face of a global epidemic of obesity, and some have even proved dangerous. Can semaglutide be different and offer real hope for success, defined as substantial and sustained weight loss?
Semaglutide timeline
The FDA originally approved Ozempic in 2017 to treat type 2 diabetes. But several trials showed it also led to substantial weight loss in people who took the drug compared to those who received a placebo. Some doctors consequently started prescribing it “off-label” (ideally in combination with exercise and lifestyle modification) to treat overweight and obesity.
In 2021, another formulation of semaglutide (with a slightly higher dose), sold under the brand name Wegovy, won approval specifically for weight management. And in 2022, the FDA green-lighted Wegovy for obesity in adolescents 12 and older.
Both drugs are self-administered by weekly injections (to the upper arm, abdomen, or thigh), with the dose increased gradually to minimize side effects.
A third semaglutide drug, Rybelsus, which was approved in 2019 for type 2 diabetes, is being used off-label for weight loss, too. (You may be familiar with the TV commercial that plays that “catchy” jingle about lowering the blood sugar measure A1C.) Rybelsus has received less attention than Ozempic, however, because it is not as effective at the doses used and perhaps because it comes in the form of a daily pill that has to be taken on an empty stomach after fasting, which makes it less convenient.
How does semaglutide work?
Semaglutide is a long-acting synthetic version of a hormone called GLP-1, which scientists have studied for decades. How exactly this slightly modified version of the hormone leads to weight loss is not completely understood, but rather than altering metabolism, it reduces how much food you consume. Among the proposed mechanisms, semaglutide slows gastric emptying, which affects hunger and the feeling of fullness. It also acts on appetite centers in the brain, affecting the sense of pleasure that food provides. As a diabetes drug, its presence in the gut helps regulate blood sugar.
A series of randomized placebo-controlled trials called STEP (Semaglutide Treatment Effect in People with obesity) has provided impressive results, especially compared to the modest outcomes seen for decades with other drugs used for chronic weight management. For instance, one of the key studies, the STEP 4 trial, included about 800 participants who didn’t have diabetes but were either obese (defined as having a body mass index, or BMI, of 30 or higher) or overweight (with a BMI of 27 to 29.9 and at least one untreated weight-related condition, such as hypertension, high cholesterol, or diabetes). Exercise and nutritional counseling for a reduced-calorie diet were also included as part of the 68-week study.
All STEP 4 participants took semaglutide for 20 weeks, during which time they lost an average of 10 percent of their body weight—a significant improvement over other drug treatments, for which 5 percent has been considered a good result. Participants were then randomized, with half continuing to take semaglutide and the other half switching to a placebo. Those who continued the drug shed more pounds still, while those on the placebo regained most of the weight they had lost during the study’s first 20 weeks. Overall, those taking semaglutide throughout the trial lost an impressive 17.4 percent of their body weight, on average, compared to just 5 percent for those on the placebo.
Before you STEP up to semaglutide
Results from the STEP program and other trials are clearly positive and promising so far. But there are abundant reasons for caution. Most pertinently, as the trials themselves show, semaglutide requires continuing use; stop taking it and you will regain the weight lost. In addition to thus requiring an open-ended commitment, these are early days of post-FDA approval, so real-world evidence has yet to accumulate—about both longer-term benefits and safety. The history of other weight-loss drugs, replete with high hopes and limited results, especially over the long term, serves as a cautionary tale.
How well current anti-obesity drugs are tolerated is another issue, and semaglutide is no exception. Side effects include stomach pain, nausea, vomiting, and both diarrhea and constipation—though for most people these diminish or disappear over time. More concerning, the drug carries a “black box warning” about thyroid cancer; while this warning is based on animal studies, people with a family history of medullary thyroid carcinoma are cautioned not to take it. Pregnancy is also a contraindication. Other possible adverse events include pancreatitis, gallstones, and diabetic retinopathy. Episodes of low blood sugar are uncommon, but people with diabetes, if they are taking insulin or insulin-promoting drugs such as glipizide, require monitoring, as do those with kidney disease.
Semaglutide shortages
With all the attention on semaglutide—fueled not just by positive study results but also by celebrity anecdotes and the proliferation of telehealth providers prescribing it for people who don’t have clear evidence of need for the drug—demand has outstripped supply. Norvo Nordisk is the only pharmaceutical company approved by the FDA to produce and market drugs that contain semaglutide as their active ingredient (Ozempic, Wegovy, and Rybelsus). However, because of shortages reported since last August, the FDA has been permitting other suppliers to process, package, and sell semaglutide through a murky and somewhat controversial practice known as “compounding.”
While compounding addresses the current supply problem, it opens the door to new safety concerns, with reports of deficient formulations, packaging, and instructions for self-injection. Misuse could affect dosage and administration, provoking or exacerbating side effects. Ozempic and Wegovy remain on the FDA’s official drug shortage list, which means they can be made and distributed with fewer restrictions. But after receiving reports of adverse effects from the use of compounded semaglutide, the agency warned at the end of May that such products are not FDA-approved and that they may not be safe or effective. When the shortages will end is uncertain.
The takeaway from the semaglutide shortages is that widespread misuse of these prescription drugs can adversely impact those who truly need or could benefit most from them but can’t get them—specifically people with poorly controlled diabetes and obesity rather than those who use them for vanity purposes in order to get even more svelte than may even be healthy.
BOTTOM LINE: Semaglutide is a potentially powerful treatment for individuals who are obese or who are overweight and have at least one weight-related health condition. But it shouldn’t be taken casually and without real necessity, a practice that is rampant today. As with any prescription weight-loss drug, you need to consult a physician, there are contraindications and potential side effects, and you may need regular monitoring. As noted, semaglutide requires an open-ended commitment, since stopping it leads to weight regain. Consider also that it doesn’t come cheap ($900 to $1,300 per month) and there’s no generic version. Insurance may make the drug affordable for many people, but current shortages and its sheer popularity are a recipe for turbulence in the marketplace.
Last note: Another diabetes drug that is being repurposed for weight loss is tirzepatide, marketed as Mounjaro. Currently approved only for type 2 diabetes, it’s been creating some buzz of late, too, while the FDA considers it as a treatment for obesity. It’s shown favorable results, with reduction in body weight of 10 to 20 percent from baseline, compared to placebo, over 72 weeks.
