Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs) mimic the action of GLP-1, which is a type of gastrointestinal hormone incretin. They promote insulin secretion from the pancreas associated with suppressing glucagon secretion, delaying gastric emptying, and suppressing central appetite. Clinical use of GLP-1RA has expanded rapidly since the 2010s as a promising option for diabetes treatment [1]. In 2021, US. Food and Drug Administration (FDA) officially approved semaglutide as an obesity treatment. This paves the way, where it can be used for not only diabetic patients but also non-diabetic obese people. Clinical efficacy has been known with attracting attention, and globally expanding demand has been rapidly observed [2]. The convenience of once-weekly subcutaneous injections and the high weight loss effect with average weight reduction >15% in clinical trials have attracted attention, and global demand is rapidly increasing. Such powerful appetite suppressant and weight loss effects have expanded their use to beauty and slimming purposes [3].

In developed countries such as the United States and Japan, the use of GLP-1RAs has increased too much among non-diabetic and non-obese people. This has led to two main problems. First, the drug has become in short supply, making it difficult for diabetic patients to obtain it. In Japan, the Ministry of Health, Labor and Welfare (MHLW) has called for the suspension of inappropriate use for cosmetic purposes [4]. The second problem is safety for actual administration of GLP-1RAs. They are originally used appropriately under the supervision of a doctor. In addition to gastrointestinal symptoms such as nausea, vomiting and constipation as adverse effects, they are also associated with pancreatitis, cholelithiasis and thyroid tumors. They are also associated with muscle loss due to rapid weight loss and eating disorders, such as Ozempic face with acute atrophy of face muscles [5]. Using them only for short-term cosmetic effects without understanding these increases the risk of various health damages.

Regarding GLP-1RA drugs, a new movement was observed in late May 2025. Until then, due to a shortage of genuine drugs, the distribution of compounded products (non-genuine products) at pharmacies was permitted by FDA [6]. However, the official comment of FDA determined that the shortage had been resolved and announced measures to stop the distribution of non-genuine products on May 23rd. As a result, concerns are present that GLP-1RA will be in short supply again in the near future. In a formal notice from the FDA, it was announced that non-genuine products that had been manufactured at pharmacies for GLP-1RA semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound) will no longer be legally manufactured and sold (Figure 1). Of these, the deadline for distribution of tirzepatide was March 2025, which had already passed. Furthermore, the last day for semaglutide was the previous day, May 22, 2025.

Some detailed situation as the background will be outlined below. Initially, GLP-1RA was launched as an oral hypoglycemic agent (OHA), and was later approved as an obesity treatment [7]. Then, the demand for GLP-1RA in the health field rapidly increased, and it was listed as one of the agents in the drug shortage list [6]. In such a situation, there were regulations of FDA before that "if a drug is in short supply, a combination of the drug may be prepared, provided that the requirements of the Federal Food, Drug, and Cosmetic Act are met." Based on this regulation, it was actually permitted to dispense and sell semaglutide and tirzepatide at pharmacies. Furthermore, it is noteworthy that such counterfeit products have been usually distributed at a lower price level than the genuine products.

Figure 1: Some GLP-1RA Drugs for Current Overuse and Problem.

One of the reasons for the FDA's notice would be the medical and social problems associated with this drug [8]. They include, at least in part, the sale of counterfeit drugs, the inclusion of impurities, and the inclusion of drugs in the correct amount, and other various cases [9]. Thus, as a practical matter, numerous lawsuits have been filed regarding GLP-1RAs dispensed in this way. The main manufacturers are Novo Nordisk (semaglutide) and Eli Lilly (tirzepatide). They have filed lawsuits against compounding pharmacies for cases of contaminated products, the manufacture of counterfeit drugs, and the dispensing of drugs without prescriptions. Among these, the most common case would be adulteration. In other words, compounding pharmacies have dispensed contaminated drugs or manufactured drugs in unsanitary conditions, which have led to health and medical damages [10]. Another common cause of counterfeiting is found when the dispensed drug contains less active ingredient than genuine doses and advertised.

The status of actual drug supply has been reported. One of the companies supplying counterfeit GLP-1RA was Olympia Pharmaceuticals. This company sold counterfeit drugs to more than 70,000 people per week. According to the comments of the company, it would like to "serve as many patients as possible who need it before the end of the distribution authorization period”. However, it is also true that there are situations where some patients find it difficult to continue treatment by paying the cost of genuine drugs themselves. Consequently, some kinds of measure may be required for a variety of cases as well.?

On the other hand, some discussions are present about the safety evidence of such counterfeit drugs. Some researchers and doctors are concerned about the quality of counterfeit drugs which are not under FDA control [11]. Then, the doctor in charge does not want to take on the responsibility that will come with prescribing them. They are concerned about the future situation, where FDA’s action will once again strain supplies of genuine drugs.  Other people are worried another possible situation, in which both providers and patients would get the drugs that they need no longer [12]. Some people possibly already have supply of counterfeit drugs themselves, but other people cannot obtain necessary drugs who has recently begun the GLP-1RA treatment with the drug.

In summary, GLP-1RAs certainly have the potential to bring about future revolution. It is expected that they will be applied to a wider range of disease areas, such as reducing the risk of cardiovascular disease, improving fatty liver, and even preventing Alzheimer's disease. Medical issues include high cost of the drug, unclear effects of long-term use and others. On the other hand, it is worrying that the original medical value of GLP-1RAs has been lost due to excessive beauty-oriented behavior and fragmented dissemination of information [13]. For medical and health care area, following three directions will be recommended. They are i) raising awareness of appropriate use, ii) establishing prescription guidelines and strengthening regulations, and iii) strengthening patient education. It will be essential for the healthy spread of GLP-1RAs in the future to work together to promote proper use and raise awareness among medical professionals, government officials, and industry groups.

Conflict of interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

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