Written by: Kali Weiss, MD (NUEM ‘28) Edited by: Jackie Zewe, MD (NUEM ‘26)
Expert Commentary by: Molly Estes, MD
Expert Commentary
The rise of GLP-1 receptor agonists like semaglutide and tirzepatide reflects a major shift in how we approach both type 2 diabetes and obesity. These medications are highly effective but come with a unique profile of adverse effects that affect multiple organ systems and present important considerations for emergency clinicians. As a medical toxicologist, I’d like to expand on several key areas from Dr. Goins’s excellent overview, particularly as they relate to toxicologic mechanisms and ED management of overdose and adverse effects.
Overdose and Toxicologic Considerations
Although severe toxicity is uncommon, accidental overdose of GLP-1 receptor agonists is increasingly reported, most often due to injector pen errors. Fortunately, these agents have a relatively wide therapeutic index. Most overdoses result in gastrointestinal symptoms, such as intractable nausea, vomiting, and anorexia. These typically resolve within 8 to 24 hours but can lead to clinically significant complications, including dehydration, acute kidney injury, and electrolyte abnormalities. There is currently no antidote. Management is supportive, with a focus on fluid resuscitation and antiemetic therapy.
GLP-1 agonists are generally considered low risk for hypoglycemia because their insulinotropic effects are glucose-dependent, tapering off as serum glucose approaches euglycemia. However, hypoglycemia has been reported in up to 9% of overdose cases, even in the absence of insulin or sulfonylurea co-administration, particularly in non-diabetic or lean individuals. As such, blood glucose should be closely monitored in all overdose patients.
When these exposures are reported to poison control, referral to a healthcare facility and a recommended observation period are based on symptom severity. Hospitalization may be required for persistent vomiting, significant hypoglycemia, or complications such as pancreatitis.
Gastroparesis and Implications for Co-ingestions
Clinicians should be aware that GLP-1 agonist–induced delayed gastric emptying has potential implications in the context of co-ingestants. This pharmacologic gastroparesis can unpredictably delay absorption of other orally administered drugs, potentially altering expected toxicokinetics. For example, in a patient with intentional overdose who is also on a GLP-1 agonist, the time to peak concentration of co-ingested agents may be prolonged, complicating risk assessment, decontamination decisions, and timing of antidotal therapies.
Counterfeit GLP-1 Agonist Products
A particularly alarming complication recently reported involves counterfeit GLP-1 agonist pens, especially fake Ozempic pens, which were found to contain insulin instead of semaglutide. These falsified products have led to cases of profound hypoglycemia, some requiring intensive care. Clinicians should be alert to this possibility when evaluating patients presenting with unexplained hypoglycemia who report GLP-1 agonist use, especially if obtained from non-pharmacy sources or online. Public health agencies have issued warnings about these counterfeit pens, underscoring the importance of verifying medication sources and educating patients on the dangers of purchasing injectables through unofficial channels.
Looking Ahead
The increasing popularity of GLP-1 agonists outside traditional diabetic populations means emergency physicians will continue to see complications from these agents. As availability expands and public interest surges, misuse, off-label use, and dosing errors are likely to rise as well. Overall, GLP-1 agonists present a novel but manageable profile of ED-relevant toxicities. A thorough medication history, a high index of suspicion for delayed gastric motility, and an understanding of the broader pharmacologic effects of these agents are essential tools for the emergency clinician. In cases of overdose or unclear presentations, consultation with your local poison center or a medical toxicologist can help guide nuanced care.
Molly Estes, MD
Assistant Professor
Northwestern University Feinberg School of Medicine
Department of Emergency Medicine
How To Cite This Post:
[Peer-Reviewed, Web Publication] Weiss, K. Zewe, J. (2025, July 31). Myxedema Coma [NUEM Blog. Expert Commentary by Estes, M]. Retrieved from http://www.nuemblog.com/blog/kw-myxedema.
