Health,  Life

Beyond the Hype: Semaglutide – A Weight Loss Revolution or Risky Shortcut?

Recently, the marketing application for a new indication of a pharmaceutical product from Novo Nordisk gained approval from the State Food and Drug Administration, garnering considerable attention.

As a multinational pharmaceutical powerhouse, it is customary for Novo Nordisk to seek new indications for its products. However, what distinguishes this occasion? Ultimately, the spotlight falls on a medication known as Ozempic or Wegovy—its renown spans Europe and the United States, so much so that tales of its “miraculous effects” on weight loss have reached the ears of many in China.

The principal component of this medication is “semaglutide,” presently approved for diabetes treatment in China. Across Europe and the United States, semaglutide enjoys a reputation as a “miracle drug for weight loss,” renowned for its purported efficacy sans dietary restrictions or exercise—weight loss through mere injection.

Last August, Elon Musk, having achieved weight loss success, took to social media to endorse Wegovy, captivating numerous followers.

Paradoxically, while videos tagged with #Ozempic amass over 600 million views on short video platforms, diabetics find themselves in a state of anxiety as they struggle to procure their medication. Increasingly, individuals not fitting the semaglutide indication rush to acquire it, to the extent that the U.S. Food and Drug Administration (FDA) listed Ozempic and Wegovy among dozens of drugs in short supply.

The pursuit of beauty is inherent in human nature, and the desire for the so-called “perfect body” is understandable. Yet, it is undoubtedly absurd to aspire to thinness without exertion, relying solely on pharmaceuticals to achieve such an effect. Every medication has its designated use, and given the current state of scientific and technological advancement, there exists no weight loss “miracle drug” devoid of side effects, universally suitable for all.

A Revolutionary Discovery

Semaglutide stands as a long-acting agonist of the glucagon-like peptide-1 receptor (GLP-1), a class of drugs highly regarded in the realm of diabetes treatment.

GLP-1 is a naturally occurring hormone in the intestines, enhancing insulin secretion postprandially while inhibiting glucagon secretion, thereby reducing blood sugar levels and suppressing appetite.

Semaglutide represents the most potent intervention for weight loss outside of gastric resection.

As early as 2005, the FDA approved the first GLP-1 drug, exenatide, for type II diabetes treatment. Subsequently, Novo Nordisk introduced its iteration, liraglutide, four years later, albeit requiring twice-daily injections due to technological constraints.

The true breakthrough occurred in 2017 with Novo Nordisk’s introduction of Ozempic, a semaglutide injection with a prolonged half-life of seven days, necessitating only weekly administration. In 2019, the oral semaglutide tablet Rybelsus received marketing approval, both representing technological advancements that significantly eased patient burden and paved the way for future popularity.

In February 2021, a study conducted by Northwestern University, published in the prestigious New England Journal of Medicine, examined the weight loss efficacy of semaglutide. Enrolling over 1,900 overweight/obese adults without diabetes across 129 sites in 16 countries spanning Asia, Europe, and the Americas, the study demonstrated remarkable outcomes.

After 68 weeks of treatment, the treatment group receiving 2.4 mg of semaglutide weekly experienced an average weight loss of 14.9%, with over a third of participants shedding more than 20% of their body weight—an average loss of 15.3 kg—far surpassing the 5% weight loss threshold typically considered for weight loss medications. In contrast, the placebo group exhibited a mere 2.4% average weight loss, equivalent to 2.6 kg.

Perhaps attributable to these findings, in June of the same year, the FDA approved another semaglutide injection, Wegovy, for use in obese or overweight patients, marking the first approval since 2014 for long-term weight management in adults with general obesity or overweight.

According to an FDA official from the Center for Drug Evaluation and Research, “Semaglutide offers a valuable new treatment option for this demographic.”

According to the publication “New Scientist,” semaglutide represents the most potent intervention for weight loss apart from gastric resection surgery, heralding a “paradigm shift” in weight loss strategies. In an interview with The Washington Post, some researchers hailed semaglutide’s efficacy as “sufficiently transformative.”

Endorsed by the FDA and esteemed scientists, semaglutide swiftly garnered significant attention in Europe and the United States. During prime time on major American TV networks, the hypnotic advertising jingle of “oh oh oh Ozempic” captivated audiences.

Last year, Elon Musk shared his successful weight loss journey, attributing it not only to regular fasting but also to Wegovy. This deliberate or inadvertent “endorsement” perpetuated semaglutide’s popularity, with individuals from various backgrounds eagerly sharing their experiences and marveling at its efficacy, dubbing it a “miracle.”

The Stars’ Secret

At the 95th Academy Awards this year, host Jimmy Canmore teased that numerous Hollywood stars have embraced Ozempic for weight loss, further fueling its popularity. Amidst the surge, one tends to overlook semaglutide’s primary purpose as a diabetes medication.

Following the semaglutide craze, diabetics reliant on the drug faced shortages, forcing some to reduce doses or switch to alternative medications.

The Daily Mail, citing data from third-party analytics firms, reported a staggering surge in semaglutide prescriptions in the United States last year, totaling 5 million compared to just 230,000 in 2019—an exponential increase of over 2,000% within a few short years.

Since April of the previous year, semaglutide has been listed among the drugs facing shortages by the FDA, a situation persisting as of May this year. According to the European Medicines Agency (EMA), semaglutide is expected to experience prolonged stock shortages, with no respite anticipated this year.

Amidst this scenario, numerous unscrupulous vendors have resorted to illicit practices, leading to the emergence of a “black market” in the United States, where semaglutide is either resold or counterfeit “generic” versions are peddled.

In response, the FDA issued a warning advising patients against the use of unbranded semaglutide. According to FDA sources, semaglutide sold online under the guise of “for laboratory research” or compounded by pharmacies lacks approval, with neither its safety nor efficacy guaranteed.

Exercise Caution with Ozempic

Objectively assessing the situation, while semaglutide indeed offers advantages compared to traditional weight loss medications, the ongoing fervor surrounding its promotion often overlooks its side effects and suitability for users.

Firstly, consideration must be given to the target demographic. The World Health Organization advocates employing body mass index (BMI) as a measure of obesity prevalence within populations. As per the prevailing practices in numerous countries, including those of the FDA, only individuals with a BMI of ≥27 accompanied by conditions such as hypertension, hypercholesterolemia, or cardiovascular disease are eligible for pharmacological intervention. In the absence of comorbidities, a BMI of ≥30 is typically required.

According to the “Report on the Status of Nutrition and Chronic Diseases of Chinese Residents (2020),” the average height of adults aged 18-44 is 169.7 cm for men and 158 cm for women. Consequently, individuals of average stature only meet the threshold for weight loss medication usage when weighing ≥86.4 kg for men and ≥74.9 kg for women in the absence of comorbidities. However, observations indicate that the vast majority of individuals advocating weight loss fail to meet these criteria.

Regarding side effects, the aforementioned study published in the New England Journal of Medicine identified nausea and diarrhea as the most common adverse reactions. Other studies have reported severe headaches, acute kidney injury, and gastrointestinal complications, rendering it unsuitable for individuals with gastrointestinal disorders.

In an April report, the EMA highlighted findings from rodent studies suggesting that tirzepatide, another GLP-1 drug, may elevate the risk of thyroid cancer. UK health authorities have consequently called for research to monitor potential associations between these drugs and thyroid and pancreatic cancers.

The Daily Mail expressed concerns over the relatively brief 16-month duration of Wegovy’s clinical trial, suggesting potential oversight of significant long-term side effects.

For many weight loss methods, rebound weight gain poses a formidable challenge. In April, a study conducted by the University of Liverpool found that participants using Wegovy experienced an 18% weight loss over 68 weeks. However, following cessation of weekly injections, the 336 trial participants regained two-thirds of their lost weight within the subsequent year.

Moreover, excessively rapid weight loss can induce significant physiological changes such as hair loss and skeletal emaciation. Diminished facial fat resulting from weight loss can lead to a less “plump” appearance than when at a higher weight. If weight loss progresses too swiftly, facial structures may fail to adapt accordingly, resulting in pronounced facial hollowing—a phenomenon colloquially dubbed “Ozempic face” by American internet users.

Dr. Zhaoping Li, a professor of medicine and chair of the Department of Clinical Nutrition at UCLA, cautioned in an interview with The Washington Post that semaglutide is not universally effective, emphasizing that “these new drugs are valuable tools in a physician’s arsenal but are by no means a panacea.”

There exists no universal remedy for weight loss, and semaglutide is no exception. Presently, semaglutide is not approved for weight loss purposes in China, with only one medication, orlistat, approved for obesity or overweight treatment—a drug which has been criticized for its tendency to induce gastrointestinal discomfort.

In entertaining fantasies of achieving weight loss through pharmaceutical means, one must heed Zweig’s poignant reminder that all gifts bestowed by fate carry a concealed price tag. Those outside the scope of semaglutide’s intended use, yet pursuing it for weight loss, ought to reflect on whether weekly injections, alongside the prospect of hair loss, facial hollowing, and loose skin, align with their aspirations.

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