Examining Off-Label Prescribing of Ozempic for Weight-Loss

Ozempic (semaglutide) is a US Food and Drug Administration (FDA) approved medication for the treatment of type 2 diabetes and more recently has been utilized in the management of chronic weight management in some patients. It belongs to a broader class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists which help to lower the blood sugar levels of individuals with type 2 diabetes. There has been growing recent interest, especially on social media platforms such as Tik Tok, about the use of Ozempic for weight loss. While Ozempic has shown promising results in clinical trials for weight loss, there are several potential risks and concerns associated with its use. There is a lack of adequate long-term safety data on its use specifically for weight loss. Growing concerns around Ozempic include its potential misuse without proper medical supervision or its prescription off-label for weight loss leading to prescription shortages. Both of these are pressing concerns surrounding the use of this medication without medical need and ultimately resulting in risky and unnecessary medical interventions. Further study is needed in order to assess and communicate the long-term effects of Ozempic for weight loss, and health policy changes to ensure safe access.


Introduction
Ozempic, also known as semaglutide, was FDA approved in 2017 for the treatment of type 2 diabetes in adults. However, it has recently risen in prevalence as individuals have shown that Ozempic can also lead to significant weight loss in patients with and without diabetes. In a clinical study, subjects taking 1mg/week of Ozempic lost nearly 10 pounds over 30 weeks, nearly 5% of their body weight, and a waist shrinkage of 1.6 inches (Sorli et al., 2017). The use of Ozempic, offlabel for weight management, was further popularized via social media (Shmerling, 2023). It is believed that Ozempic induces weight loss mechanistically through delayed gastric emptying, mimicking glucagon-like-peptide-1 (GLP-1), reducing liver fat, and improving insulin sensitivity. In June 2021, the FDA approved Wegovy, a higher-dose formulation of semaglutide compared to Ozempic, for weight management. However, Wegovy has recently undergone a shortage which has led Ozempic to be utilized off-label by individuals seeking to lose weight (Shmerling, 2023). Physicians may prescribe a drug off-label in order to take advantage of new treatment approaches before FDA approval, but this is without the benefit of an FDA-reviewed analysis of safety and effectiveness data (Congressional Research Service, 2023). However, the off-label prescribing of Ozempic may interfere with the availability of Ozempic for individuals with diabetes. As of this article, the hashtag #ozempic on Tik Tok has 931.8 million views and it is rapidly becoming associated as a "vanity" medication rather than a critical treatment for individuals with diabetes. Many are also troubled by social media platforms heralding Ozempic as a quick, cosmetic weight loss drug when it is, in fact, for long-term use as discontinuation can result in weight gain. A recent study found one year after the withdrawal of once-weekly Wegovy (2.4mg) and lifestyle intervention that participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables (Wilding et al., 2022).

Off-Label Prescribing and Reduced Availability
Off-label drug use is defined as drug use for an unapproved indication, population, or dosage ( Hendricks, 2017). The use of Ozempic as a weight-loss drug has risen due to online popularity. As obesity is a major factor in contributing to type 2 diabetes, Ozempic has major implications for managing both diseases. In obese individuals, insulin resistance is increased due to hormones, cytokines fatty acids, and other markers (Al-Goblan et al., 2014). Weight reduction is encouraged to reduce these markers to improve insulin sensitivity (Al-Goblan et al., 2014). Although weight loss can aid in obesity and type 2 diabetes, the risks of the potential complications of off-label use of Ozempic can be a concern.
Patients who received semaglutide for weight loss had significant loss in body weight compared to those who received a placebo (Wilding et al., 2021). Initially, researchers have concluded that the long-term effect of GLP-1s have not been studied and remains unknown (Baggio and Drucker, 2007). However, after several years of clinical trials, semaglutide has been studied extensively.
With off-label prescribing, there is a potential for harm and adverse effects and patients can be exposed to unknown risks.
Informed consent is also compromised, as patients may not have all the information needed to make well-informed medical decisions for treatment. While off-label prescribing can provide patients with alternative options that may be better Qeios, CC-BY 4.0 · Article, June 6, 2023 Qeios ID: T6Y97S · https://doi.org/10.32388/T6Y97S 2/7 suited for them, there are some drawbacks for individuals who rely on Ozempic for its prescribed, FDA-approved utilization. As demand inevitably increases with off-label prescribing, a shortage of Ozempic is likely, and those with type 2 diabetes may struggle to access the medication. Thus it is up to healthcare providers to understand and evaluate each patient for an appropriate prescription (Hendricks, 2017).

Alternative Medications To Ozempic
Liraglutide (Saxenda), Phentermine/Topiramate (Qsymia), and Orlistat (Xenical) are alternative medications prescribed for weight loss. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that promotes satiety and reduces appetite. It is available in doses of 0.6mg, 1.2 mg, and 1.8mg per day, injected subcutaneously. Weight loss is dose-dependent; however, a mean reduction of -2.3kg has been recorded (Dharmalingam et al., 2011). Phentermine/Topiramate is a combination medication that suppresses appetite and increases feelings of fullness. Phentermine is a sympathomimetic amine that acts centrally as an appetite suppressant, while topiramate is an anticonvulsant drug that can also reduce appetite. The typical starting dose is phentermine 3.75 mg/topiramate 23 mg, gradually increasing over a few weeks to the recommended dose of phentermine 7.5 mg/topiramate 46 mg (Cosentino et al., 2013). Clinical trials have shown that phentermine and topiramate treatment can result in significant weight loss, with an average of around 5-15% over a year (Cosentino et al., 2013). Orlistat is a lipase inhibitor that works by preventing the absorption of dietary fats. It is available in doses of 10mg, 60mg, 120 mg, and 240 mg three times daily. Orlistat has been found to lead to modest weight loss, with studies indicating an average reduction of -3.19 kg after 1 and 2 years (O'Meara et al., 2004).
In comparison to semaglutide (Ozempic), which is also a GLP-1 receptor agonist, liraglutide has a similar mechanism of action. Both medications increase satiety and reduce appetite. However, semaglutide has been found to be more efficacious than liraglutide in weight loss. Clinical trials have shown that semaglutide can lead to an average weight loss of around -4.53kg after a 30-week period in comparison to an average of -2.3kg after 52 weeks which is higher than the weight loss observed with liraglutide. Liraglutide and semaglutide are known to cause gastrointestinal adverse effects such as nausea, vomiting, and diarrhea (Dharmalingam et al., 2011). Phentermine/topiramate may induce dry mouth, constipation, paresthesias of the extremities, and insomnia as side effects. Orlistat can lead to gastrointestinal side effects such as oily spotting, flatulence, and urgency to urinate. It is important to note that, due to their effects on decreasing blood sugar, liraglutide and semaglutide are approved for the treatment of type 2 diabetes. Orlistat and phentermine/topiramate, on the other hand, are not recommended for the management of diabetes. All of these medications can contribute to weight loss, but their efficacy, dosages, expected results, and adverse effects may vary.

Social Media's Impact On Off-Label Prescribing
Social media platforms have opened channels for communication and dissemination of information online (Vrontis et al., 2021). A fairly recent avenue of marketing, known as influencer marketing, utilizes an individual's presence on social media for advertisement and endorsement of their product (Jin et al., 2019), Included in this category of influencers are Qeios, CC-BY 4.0 · Article, June 6, 2023 Qeios ID: T6Y97S · https://doi.org/10.32388/T6Y97S 3/7 "patient influencers" who work with pharmaceutical companies to leverage the patient experience and expertise for the design, development, and promotion of their products and services (WEGO Health, 2023). Patient influencers aim to increase awareness and promote education on that particular disorder/disease by sharing experiences of their own (Willis and Delbeare, 2022). Pharmaceutical companies often garner little trust, however, by involving patient influencers they are able to separate the product from the brand to allow for better results (Singh et al., 2023). In fact, past research has reported that 44% of patients who requested medication advertised to them were then prescribed to them by their physician (Willis and Delbeare, 2022). Patient influencers often share their experiences on social media allowing for public conversation and debate on the topic. However, this practice often increases the chances of spreading misinformation and malpractice. A multitude of factors such as health literacy and scientific communication strategies may determine the understanding of the medication and its use. For example, in the context of Ozempic, individuals taking this medication off-label for weight loss experienced serious side effects such as diarrhea, nausea, and extreme facial thinning (Singh et al., 2023). Its popularity among patients especially on social media platforms such as TikTok, Twitter, and Instagram garnered attention and others were quick to notice the effects of the drug especially on appetite and weight loss (Singh et al., 2023). This shift in focus was undoubtedly one of the driving factors for the use of this drug for weight loss instead of diabetes and the shortage that followed.
Additionally, the exposure of Ozempic as a weight loss drug was exacerbated when popular celebrities were suspected to be using it. For example, the use of Ozempic by popular reality-tv celebrities further established the off-label use of this medication. Social media exposure of such kind has been linked to psychological disorders such as body dysmorphia, anorexia nervosa, and bulimia (Becker, 2004). Hence, it calls into question the effectiveness of social media marketing. It is important to consider the important role that social media/patient influencers played in presenting a drug, originally intended and marketed for patients with type-2 diabetes, as a miracle off-label drug for weight loss. While recent research has started to address these issues, we are nowhere closer to resolution. Pharmaceutical companies must address and control the impact their medication has on the general public by ensuring their patient influencers are given the necessary education and resources to successfully communicate the scope of the drug. In addition, further care must be taken to oversee the content created and shared by the influencers. Misinformation must be tackled with care and patient testimonials when applicable. of obesity and would stand to benefit the most from significant weight loss, but are unable to access these costly medications (NBC News, 2023). The high out-of-pocket cost is unsustainable long-term for many. Some patients are turning to compounding pharmacies that can make generic semaglutide for $300/month (ABC News, 2023).
Compounding pharmacies are not without their own risks. According to the FDA, these medications are eligible for compounding given recent shortages, but the compounded versions "pose a higher risk" due to a lack of pre-market review (ABC News, 2023).
In the United States, Eli Lilly manufactures Mounjaro which performs a similar function to Ozempic and recently indicated plans for FDA approval for weight loss by the end of this year (Good Morning America, 2023). Outside of the US, Wegovy was recently approved in the United Kingdom for weigh-loss (Cosmopolitan UK, 2023). However, online pharmacies in the United Kingdom have faced criticism for filling prescriptions for Ozempic for a reporter with a BMI of 20, while the drug should be discontinued once a patient's BMI is below 27 (The Guardian, 2023). The availability of these drugs, without stringent health checks, is another cause for high concern.
Concluding Thoughts Semaglutide has been promising for treating type 2 diabetes. There are, like all drugs, potential concerns for users. For instance, during a clinical trial, the progression and worsening of diabetic retinopathy emerged (Berkovic and Strollo, 2023). But, when it is prescribed under advised conditions, semaglutide appears to be beneficial for its intended use.
Regardless, effective weight-management programs should be individualized and personalized. Patients may have other coexisting conditions, different drug tolerance, and differing economic conditions. Further studies should be conducted to draw more direct comparisons between different types of drugs prescribed for this purpose, and the efficacy of various lifestyle interventions in isolation or in tandem with these drugs. Bibliography