On June 4, 2021, the FDA announced the long-anticipated approval of Wegovy, an injectable medication taken once per week for weight management.
Wegovy received significant media attention in the months preceding approval, with a New York Times article declaring it a “game changer,” MedPage Today reporting its “unprecedented results,” and the BBC announcing it could mark a “new era” in treating obesity. Ongoing media coverage continues to extol the efficacy of Wegovy as better than any other medication currently on the market for weight management. Such sensational headlines are commonplace in the media, so we must ask ourselves: is all the media attention truly warranted?
What is Wegovy and how does it work?
Wegovy is the brand name for the high-dose injectable peptide hormone molecule known as semaglutide, a medication that was previously approved by the FDA under the brand names Rybelsus (oral) and Ozempic (lower-dose injection) for the treatment of type 2 diabetes. Injectable semaglutide eliminates the strict guidelines for ingesting on an empty stomach required by oral semaglutide, while the higher-dose Wegovy allows for better crossing of the blood-brain barrier, which increases its weight-loss efficacy.
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Semaglutide is in a class of medications known as glucagon-like peptide-1 receptor agonists, or GLP-1 RAs. GLP-1 is a hormone naturally released in the gastrointestinal tract in response to nutrient intake. It has multiple effects, including increasing insulin release from the pancreas, slowing down stomach emptying, and targeting receptors in the brain that cause appetite reduction. This results in a sensation of satiety, or fullness, lasting much longer than possible with natural GLP-1 hormone levels.
Who can take Wegovy?
Wegovy, like all other prescription medications designated for the treatment of obesity, is approved for use in those with a body mass index (BMI) of 30 kg/m2 or greater, or those with a BMI of 27 kg/m2 with a weight-related medical condition such as high blood pressure, type 2 diabetes, or high cholesterol.
What are the risks and benefits of Wegovy?
Phase 3 clinical trials of Wegovy, dubbed the STEP (Semaglutide Treatment Effect in People with Obesity) trials, were conducted in a variety of clinical scenarios, each varying slightly in the study population and study design. The widely reported STEP 1 trial, the results of which were published in the New England Journal of Medicine, demonstrated an average of 14.9% body weight reduction after 68 weeks of therapy in those assigned to the medication group, versus only 2.4% weight loss in those assigned to the placebo group. The average weight loss seen with existing anti-obesity medications is typically about 5% to 9%, while those engaged in lifestyle and behavioral therapy alone are expected to lose only 3% to 5% of their body weight.
The most common side effects of Wegovy are nausea, diarrhea, vomiting, and constipation. The medication also comes with a warning for risk of a specific tumor of the thyroid, and thus it is not recommended for those with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (a genetic condition associated with endocrine tumors). It should be noted that tumors were only observed in animal studies, and not seen in the human trials.
How long can you take Wegovy?
Wegovy is one of six medications currently approved by the FDA for the long-term treatment of obesity. As such, it can be used for as long as it remains beneficial for weight loss and/or weight maintenance and is not causing intolerable side effects. The first GLP-1 RA medication to gain FDA approval was exenatide in 2005; since then, multiple GLP-1 RAs have been approved and undergone long-term trials demonstrating either non-inferiority or superiority, when compared to placebo for major adverse cardiovascular events such as heart attacks and stroke. The SELECT trial is the long-term cardiovascular outcomes trial for Wegovy that aims to assess its effects on heart disease and stroke in patients with overweight and obesity; it is currently ongoing and expected to be completed in September 2023.
Anti-obesity medication management: An evolving landscape
Wegovy is the latest in a line of medications, starting with phentermine in 1959, that have achieved FDA approval for the treatment of obesity. Currently there are 10 FDA-approved anti-obesity medications in the US: phentermine, diethylpropion, benzphetamine, phendimetrazine, orlistat, phentermine/topiramate ER (Qsymia), bupropion/naltrexone (Contrave), liraglutide (Saxenda), setmelanotide (Imcivree), and now semaglutide (Wegovy). Of note, setmelanotide is only approved for the treatment of obesity caused by specific, rare genetic conditions. Other medications such as metformin, zonisamide, and other GLP-1 RAs normally used for treating diabetes are often prescribed “off label” and at the discretion of the prescriber for the treatment of obesity.
Medication treatment of obesity has been a tumultuous arena plagued by many instances of therapeutics being unable to demonstrate sufficient safety data to warrant FDA approval, such as rimonabant (Acomplia); or of adverse effects necessitating market withdrawal, such as lorcaserin (Belviq), sibutramine (Meridia), dexfenfluramine (Redux), fenfluramine (Pondimin), and the infamous combination medication fen-phen — a drug which, despite its extreme popularity in the 1990s, was never actually granted FDA approval. Unfortunately, the rocky anti-obesity medication landscape often leads to discomfort among clinicians in using the many safe and effective tools we currently have for treating obesity, or worse, hesitance to address obesity as a health concern at all.
Paying for anti-obesity medications
For those who do prescribe anti-obesity pharmacotherapy, challenges arise with the exorbitant cost of some of the newer therapeutics, as well as refusal of many private and public insurers to cover anti-obesity medications. Sometimes patients or their advocates may have success in lobbying their employers to opt in to insurance coverage for obesity management. However, for those on Medicare or Medicaid, there is currently absolutely no coverage for anti-obesity medications. Patients without coverage are left with the choice of paying out of pocket for a lower-cost generic anti-obesity medication; taking a medication primarily intended for treating other medical conditions such as diabetes or seizures that may also help with weight loss; or, if their BMI and health status is severe enough to satisfy insurance requirements, they may opt for bariatric surgery, a much more widely covered insurance benefit.
The Treat and Reduce Obesity Act is a bill that was first introduced to Congress in 2012 and most recently reintroduced in 2021, with the goal of amending the Medicare Social Security Act to authorize insurance coverage of obesity counseling services and FDA-approved anti-obesity medications. This remains the largest hurdle in the obesity treatment landscape: gaining sufficient buy-in from government agencies, employers, and insurers by convincing them that medications targeting the most prevalent chronic disease in the US are actually worth paying for.