Abstract
Recent FDA approval of new GLP-1 agonists drugs focused on weight loss has been met with a surge in use of drugs such as Wegovy® and Zebound®. These drugs have shown to be very effective in producing weight loss in patients. Unfortunately, the surge in use of these drugs has also translated into a huge increase in accidental overdoses.
In addition, counterfeit drugs as well as compounded drugs, which may not contain the same active ingredient as FDA-approved drugs, have reached the public. Just recently, in 2024, publications covering this critical topic reached emergency room clinicians.
It is critical that EMS personnel also know about this new class of drugs and potential for accidental overdoses. Most commonly, patients will present with a variety of generalized symptoms including, but not limited to, nausea/vomiting, dehydration, hypoglycemia, diarrhea and abdominal pain.
EMS personnel should pay particular attention to fluid status. If the patient is dehydrated from hypovolemia, then fluid resuscitation may be indicated along with an antiemetic if nausea/vomiting are present.
Introduction
New solutions to diabetes control and weight loss have been approved for use. Ozempic® was the first semaglutide drug, an GLP-1 (glucagon-like peptide 1) agonist and was approved to help improve blood sugar levels in patients with Type II diabetes in 2017.1
Previously, multiple other GLP-1 agonists reached the public (Table 1). However, the recent FDA approvals of Wegovy® (2021) and Zebound® (2023) for weight loss have been met with a tremendous increase in demand for these drugs.2,3
Since then, the use of these drugs became popularized by different celebrities such as Elon Musk and Oprah Winfrey. Between 2019 and December 2023 there has been a greater than 932% increase in prescriptions for semaglutide medications.4
Unfortunately, with the surge in semaglutide and related prescriptions, which has been exacerbated by compounded (see below) GLP-1 drugs also reaching the public, there has been a surge in calls tracked by America’s Poison Centers, reaching almost 3,000 calls in 2023.4,5
Given the popularity of semaglutide’s and related drugs, Emergency Medical Services (EMS) need to be aware of the potential emergencies that may be encountered.
GLP-1 Pharmacology
Glucagon-like peptide 1 agonists simulate the action of incretin, which is a hormone produced by the small intestines, that bind to the GLP-1 receptor.6 The GLP-1 receptor is found on many organs including the pancreas, gastrointestinal tract, heart, and kidneys, to name a few.
This hormone has multiple mechanisms of action, all potentially useful in the treatment of diabetes as well as weight loss. In addition to stimulating insulin secretion, these drugs can reduce glucagon production and peak postprandial glucose levels.
GLP-1 agonists can also increase satiety, reduce feelings of hunger, delay gastric emptying, decrease food cravings, and result in an improvement in eating control. It should not be surprising that most of the side effects are related to the mechanism of actions and can be somewhat predicted by the anatomical location of the GLP-1 receptors.
This also explains the potential medical issues that paramedics may have to recognize and manage.
Adverse Events
The dramatic increase in demand for GLP-1 drugs has also resulted in a surge in calls to poison centers and EMS. This is both to address the side effects from FDA-approved drugs when used appropriately, as well as from accidental overdoses.
This problem has been potentially made worse by the availability of counterfeit, as well as compounded, semaglutide drugs.7 In this regard, compounding pharmacies may prepare a version of the drug when there is a reported shortage, as is the case with Ozempic® and Wegovy®.
The FDA has published warnings alerting the public, pharmaceutical manufactures, and compounding pharmacies to be aware that some products may not contain the same active ingredients as FDA-approved semaglutide products.8
Case reports of accidental overdoses, as well as guidance to emergency room clinicians, have also begun to appear in the clinical and pharmacy literature. 9-11
Expected side effects of this class of drugs are mainly focused on the gastrointestinal tract. Expected side effects at prescribed doses include nausea, vomiting, diarrhea and abdominal pain.6,10
Paramedics should also be watchful for hypoglycemia, especially when combined with other drugs used to treat diabetes, as well as pancreatitis or biliary disease. Hypersensitivity reactions, including anaphylaxis, have been reported as well.
The Missouri Poison Center has listed signs of a semaglutide overdose described in Table 2.12 Data from New Mexico Poison Center also reports that 43% of people who called about accidental semaglutide overdose did require immediate medical attention.13
Table 2: Signs and Symptoms of Semaglutide Overdose12
Feeling lightheaded or dizzy
Feeling shaky or jittery
Sweating, chills and clamminess
Irritability or impatience
Headache
Weakness
Fatigue
Nausea and/or vomiting
Seizures
Altered Mental Status
Syncope/Near Syncope
Hypotension
Lastly, it is important to note that most calls for help related to semaglutide overdoses are from adults ages 40-70, with the largest group in the 60 to 69 range.5 This is in contrast to the typical call for most accidental overdoses involving children.
Guidance to Paramedics and EMS Personnel
When EMS personnel encounter a patient who is taking a semaglutide they should start with performing a thorough patient assessment with a heightened focus on fluid status, blood pressure, mental status and blood glucose level.
There are several names for FDA-approved semaglutide medications (Table 1); however, EMS personnel need to be alert for the use of counterfeited drug as well. The patient may only be familiar with the brand name of the semaglutide they are prescribed.
The acute side effects that EMS may be called for are generally gastrointestinal in nature. If the patient is experiencing gastrointestinal symptoms, EMS personnel should assess for recent increase in dose with their prescribed semaglutide medications, as increasing the dose of semaglutide medications may trigger gastrointestinal symptoms. EMS personnel should pay particular attention to fluid status and potentially assess for orthostatic changes.
If the patient is dehydrated from hypovolemia, then fluid resuscitation may be indicated along with an antiemetic if nausea/vomiting are present. In addition, hypoglycemia should be considered and determined in all patients being evaluated, but especially in diabetic individuals.
Summary and Conclusions
There has been a tremendous increase in the use of GLP-1 medications in patients with diabetes, as well as for weight management. Accompanying the increase in use of these drugs has been a surge in individuals seeking guidance regarding their side effects, as well as accidental overdoses.
As a result, EMS personnel need to be aware of these new medications and how to best assess and manage patients exposed to these drugs. Particular attention should be focused on fluid status and the potential for hypoglycemia, though a variety of reactions may be observed.
References
- Ozempic prescribing information/package insert. Available from FDA Website: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209637s003lbl.pdf.
- Wegovy prescribing information/package insert. Available from FDA Website: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf.
- Zebound prescribing information/package insert. Available from FDA Website: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217806s000lbl.pdf
- Benadjaound Y, Kindelan K, Krill L. Poison control centers report increase in calls related to drugs used for weight loss. https://abcnews.go.com/GMA/Wellness/poison-control-centers-report-increase-calls-related-drugs/story?id=105685860
- Goodman B. Poison centers see nearly 1,500% increase in calls related to injected weight-loss drugs as people accidentally overdose. https://www.cnn.com/2023/12/13/health/semaglutide-overdoses-wellness/index.html
- Moore P, Malone K, VanValkenburg D, Rando LL, Williams BC, Matejowsky HG, Ahmadzadeh S, Shekoohi S, Cornett EM, Kaye AD. GLP-1 agonists for weight loss: Pharmacology and clinical implications. Adv Ther 2023;40:723-742. PMID: 36566341.
- Lambson JE, Flegal SC, Johnson AR. Administration errors of compounded semaglutide reported to a poison control center-Case series. J Am Pharmacists Assoc 2023;63:1643-1645. PMID: 37392810.
- FDA warns consumers not to use counterfeit Ozempic (semaglutide) found in US drug supply chain. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-use-counterfeit-ozempic-semaglutide-found-us-drug-supply-chain.
- Wiener BG, Gnirke M, Vassallo S, Smith SW, Su MK. Gluts of GLP-1: A case series of semaglutide overdose through administration errors. (Abstract) J Med Toxicol 2023:19(2):63-168.
- Long B, Pelletier J, Koyfman A, Bridwell RE. GLP-1 agonists: A review for emergency clinicians. Am J Emerg Med 2024:78:89-94. PMID: 38241775.
- Elmehdawi RR, Elbarsha AM. An accidental liraglutide overdose: case report. Libyan J Med 2014:9 online. PMID: 24461534.
- Can you overdose on Ozempic for weight loss. Missouri Poison Center. https://missouripoisoncenter.org/can-you-overdose-on-ozempic-for-weight-loss/.
- Accidental overdoses of injected weight loss drugs are surging. https://www.everydayhealth.com/weight/accidental-overdoses-of-weight-loss-drugs-ozempic-and-wegovy-are-surging/
