GLP-1 receptor agonists (GLP-1 RAs), of which semaglutide is an example, have emerged as a prominent therapeutic option for managing type 2 diabetes. A landmark side effect of the class of drugs is weight loss, sparking intense enthusiasm for the drug from patients, providers, and the media. The high demand, resulting in drug shortages, has prompted the introduction of compounded forms into the market. As the complexities surrounding GLP-1 RAs continue to develop, the associated medicolegal risks are evolving, as well. The following is an overview of the increasingly popular medication and considerations for prescribing it.
What Is Semaglutide?
GLP-1 RAs act by mimicking the action of the endogenous incretin hormone GLP-1. By binding the GLP-1 receptor on pancreatic beta cells, the drug enhances glucose-dependent insulin secretion and improves glycemic control. Additional physiologic actions of semaglutide include suppression of glucagon secretion, slowing of gastric emptying, and promotion of satiety, which collectively contribute to reduced postprandial glucose levels. Several GLP-1 RAs are currently available, and three are FDA approved: Ozempic®, Rybelsus®, and Wegovy®. GLP-1 RAs are available by prescription only and there are no approved generic products.
Considerations
While GLP-1 RAs are generally well tolerated, their side effects profile has drawn attention. These include nausea, vomiting, diarrhea, and abdominal pain. Severe adverse events associated with use include acute pancreatitis, thyroid abnormalities, gastroparesis, ileus, bowel obstruction, gallbladder disease, and allergic reactions. To detect and manage adverse events promptly, regular monitoring of patients is essential.1
A comprehensive medical history, to include pancreatic and thyroid disorders, is essential prior to initiating GLP-1 RA therapy. A shared decision-making process is critical to mitigating the risk associated with the side effect profile of GLP-1 RAs. Patient education, to include the potential side effects, risks, monitoring parameters, and the importance of follow-up should be documented. These elements, along with a discussion of alternative therapies and the associated risks of alternative therapies (or doing nothing), are essential to an adequate informed consent process.
Informed Consent
Providers must be aware of the standard for informed consent in the state in which they practice, as it varies by state. Colorado and Nebraska, for example, use the “professional standard,” while Iowa requires a “patient standard.” A professional standard means that the patient must be informed to the extent a reasonable physician in the same specialty, at the same time, would have under the same or similar circumstances. Expert testimony is needed to establish the scope of a physician’s duty of disclosure. A patient standard, in contrast, establishes the physician’s duty to disclose is determined by whether a reasonable person in the patient’s position would consider the information material to the decision of whether to undergo the proposed treatment. Information is material if it would be viewed as significant in deciding whether to consent to the treatment. Deciding what information is material depends on the facts and circumstances of each case and is decided by a jury.
Compounded Forms of Semaglutide
In response to drug shortages and patient demand, compounded versions of GLP-1 RAs, specifically semaglutide, are commercially available (with and without a prescription). Compounding is the process of combining or altering ingredients to create a medication tailored to the needs of an individual patient. It is important to note that compounded drugs are not FDA approved and the agency does not verify their safety or efficacy.2
Compounded forms of semaglutide often utilize the salt forms of semaglutide, differing from the active base form contained in the approved drugs. According to the FDA, the salt forms of the drug have not been evaluated for safety and efficacy and therefore do not qualify for the compounding exemption under the laws for drugs experiencing shortage. The FDA has warned consumers not to purchase the compounded forms of semaglutide.1
Evolving Risks
Disturbingly, poison control centers have seen a 1500% increase in calls related to injected forms of semaglutide in 2023.3 The overwhelming majority of the overdoses were related to dosing errors on the part of the patient. The compounded versions are thought to be the cause to the increase in calls, as these solutions require patients to draw their own doses as opposed to receiving the brand-name prefilled pens.
All legal proceedings involving semaglutide are in their infancy and COPIC will continue to monitor them. As with any medication, to minimize your risk when prescribing semaglutide, adherence to prescribing guidelines and a thorough shared decision-making process to include the risk and associated side effects of use, and close follow-up of patients, are essential.
1 Medications Containing Semaglutide Marketed for Type 2 Diabetes or Weight Loss. U.S. Food and Drug Administration, 2024. www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss
2 Compounding and the FDA: Questions and Answers. U.S. Food and Drug Administration, 2022. www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers
3 Glucagon-like Peptide-1 (GLP-1) Agonists. America’s Poison Centers, 2024. www.aapcc.org/track/GLP-1
Information in this article is for general educational purposes and is not intended to establish practice guidelines or provide legal advice.
Article originally published in 2Q24 Copiscope.
