Compounded and counterfeit semaglutide poses a serious risk to patients

It’s no secret that public interest in glucagon-like peptide 1 (GLP-1) agonists has been growing rapidly, and the search popularity of semaglutide (Ozempic; Novo Nordisk) grew exponentially between March 2018 and February 2023, according to an article. published in Journal of Aesthetic Surgery. Ozempic, according to the authors, remained the most searched drug compared to semaglutide (Wegovy; Novo Nordisk) and tirzepitide (Mounjaro; Eli Lilly) during the same time period.¹

Prescriptions for those drugs also increased, with users of Ozempic increasing from 569 patients in 2019 to 22,891 in 2022. Meanwhile, Wegovy increased from 989 patients in 2021 to 2,992 in 2022, according to a 2022 study. Journal of the American Pharmacists Association. The authors stated that the monthly growth rates were 83.9% for Ozempic, 119.2% for Wegovy and 254.3% for Mounjaro.²

Ozempic and Rybelsus (Novo Nordisk), a semaglutide tablet, are indicated as an adjunct to diet and exercise to improve glycemic control for people with type 2 diabetes (T2D), and Ozempic also has an indication to reduce risk of heart attack, stroke. , and death in adults with T2D.³ Wegovy is indicated for obese or overweight people with weight-related medical problems in addition to diet and exercise.³ Most recently, the FDA approved a new indication for Wegovy for the reduction of the risk of cardiovascular death, heart attack, and stroke in patients with cardiovascular disease and obesity or overweight.⁴

Despite these indications, Ozempic, Wegovy, and Mounjaro have been used off-label for cosmetic weight loss. Medical spas, in particular, have become a major source of these drugs for patients seeking to lose weight for cosmetic purposes. Medical spas are a combination of a cosmetic medical center and a day spa, which may include non-surgical cosmetic medical services by a licensed physician, according to the American Society of Plastic Surgeons.⁵ At medical spas, common medical interventions include deoxycholic acid (Kybella; Allergan Aesthetics, AbbVie) or semaglutide. Deoxycholic acid is the only injectable fat-dissolving drug that is FDA-approved, but it is only approved for fat under the chin, according to the FDA.⁶ In some cases, the drug has been used on other parts of the body, such as the back, thighs, upper arms and stomach, but these uses are not currently approved. The FDA has spoken out against the use of these drugs for unapproved indications, saying that this has led to adverse events (AEs).⁶

Similarly, semaglutide has been used off-label for cosmetic weight loss in medical spas. In particular, the drug can be combined, resulting in some composition-related AEs. Compounded medication does not go through rigorous FDA review for safety, quality, or efficacy, but is permitted under the federal Food, Drug, and Cosmetic Act when there is a drug shortage. The FDA has reported that some compounds of semaglutide have used salt forms of the drug, which have different active ingredients than the approved formulation. The agency stated that it is not aware of any drug compound that can be used in salt form that meets the requirements of the federal Food, Drug, and Cosmetic Act.³

According to a letter to healthcare providers in 2023, there were 352 cases of IEs associated with compound semaglutide, with 268 classified as serious. According to Novo Nordisk, 84 cases required hospitalization and 5 involved deaths. In addition, the company stated that some entities have been selling the compound drug in combination with BPC-157, which the FDA has banned in the compound due to safety risks.⁷

Also, regarding impurities, Novo Nordisk has said compounded drugs sometimes contain peptide-related impurities not found in the FDA-approved formulation, with the level of unknown impurities as high as 33% in some cases When present, the impurities can cause serious and life-threatening reactions, including anaphylaxis, according to the letter. Also, in some cases, the strength of the composite samples was lower than the strength specified on the labels.⁷

Both Eli Lilly and Novo Nordisk have spoken out against the use of their drugs for cosmetic weight loss, with Eli Lilly stating that Mounjaro and Zepbound are indicated for the treatment of serious diseases; they are not approved and should not be used for cosmetic weight loss.⁸ In addition, Eli Lilly also said in the statement that some products that have been claimed as a tirzepitide compound contain bacteria, high levels of impurities, different chemical structures and different colors than the approved drugs. They also reported that in one case, the product was nothing more than sugar alcohol.⁸

In a statement to Pharmacy timeNovo Nordisk said it is committed to the responsible use of [the] medicines The company stated that compounded products could expose patients to health risks, so patients should be cautious and only use drugs with a prescription from a healthcare provider.

Both companies have taken legal action against medical spas, medical weight loss clinics and compounding pharmacies for false advertising, trademark infringement and illegal sale of non-FDA approved compounding products that they say contain semaglutide.⁸ As of March 18, 2024, Novo Nordisk has filed 12 legal actions against these entities. There have been 2 final judgments out of the 12 cases: one against a medical spa and one against a weight loss clinic, according to the release.

In addition to the legal actions, Eli Lilly has also released 2 films educating people about obesity as a disease and the proper use of obesity medications. In the press release, the company stated, patient safety is Lilly’s top priority and our medicines are indicated for the treatment of serious diseases. They have not been studied, are not approved, and should not be used for cosmetic weight loss, and at Lilly we believe it is important that, in consultation with their health care providers, the right people have access to these medications.⁹

Eli Lilly did not respond to requests for comment Pharmacy time.

References

1. Han SH, Safeek R, Ockerman K, et al. Public interest in the off-label use of glucagon-like peptide 1 agonists (Ozempic) for cosmetic weight loss: a Google trend analysis. Aesthet Surg J. 2023;44(1):60-67. doi:10.1093/asj/sjad211

2. Watanabe JH, Kwon J, Nan B, Reikes A. Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022.J Am Pharm Assoc (2003). 2024;64(1):133-138. doi:10.1016/j.japh.2023.10.002

3. FDA. Medicines containing semaglutide marketed for type 2 diabetes or weight loss. January 10, 2024. Accessed March 22, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type- 2-diabetes -or-weight-loss

4. Gallagher A. FDA approves semaglutide for new cardiovascular disease indication. Pharmacy time. March 8, 2024. Accessed March 22, 2024. https://www.pharmacytimes.com/view/fda-approves-semaglutide-for-new-indication-involving-cardiovascular-disease

5. Mariotti E. What to look for in a quality spa. American Society of Plastic Surgeons. March 8, 2019. Accessed March 22, 2024. https://www.plasticsurgery.org/news/blog/what-to-look-for-in-a-quality-med-spa

6. FDA. Using fat-dissolving injections that are not approved by the FDA can be harmful. December 20, 2023. Accessed March 22, 2024. https://www.fda.gov/drugs/buying-using-medicine-safely/using-fat-dissolving-injections-are-not-fda-approved- can-be – harmful

7. Brett J, Radin M. Composite letter. Novo Nordisk. February 2024. Accessed March 22, 2024. https://www.novomedlink.com/content/dam/novomedlink/semaglutide/Compounding-Letter.pdf

8. Open letter on the use of Mounjaro (tirzepatide) and Zepbound (tirzepatide). News release. Eli Lilly. March 7, 2024. Accessed March 22, 2024. https://investor.lilly.com/news-releases/news-release-details/open-letter-regarding-use-mounjaror-tirzepatide-and-zepboundr

9. The new phase of Lilly’s Get Better campaign challenges misperceptions about obesity care. News release. Eli Lilly. March 7, 2024. Accessed March 22, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-newest-phase-get-better-campaign-challenges