A patient came into my emergency room recently with profuse vomiting. They were in our rapid care unit, looking horrible. Vomit bag in one hand, box of tissues in the other, and a please just stop this look on their face.
I took a quick history between episodes of emesis. They had been vomiting nonstop, around 10 times a day, and it started after their semaglutide shot two days earlier. I asked who prescribes their medication. They told me they get it from an online GLP-1 clinic. They had just increased their dose, after already losing around 15 pounds in the first three months.
That gave me pause. So I asked the obvious question. You were losing weight. Why did they ask you to change your dose? The patient did not know. It was just what the app told them to do.
That case is the reason this article exists. Not because these drugs are bad, because they are not. Because the way a lot of people are getting them right now removes the one thing that makes them safe, which is a clinician who knows you.
The conversation around these drugs is a mess
Ozempic, Wegovy, Mounjaro and the rest of the GLP-1 family are the biggest story in medicine right now, and the public conversation about them has collapsed into two camps.
Half the internet treats them as a miracle. The other half treats them as poison. Neither is being straight with you, because these medications, like every single medication, need an honest and nuanced conversation when we talk about using them as a tool to help someone reach their health goals.
So I am going to run these drugs through the same framework I use for every medication. What are they and how do they work. What is the actual benefit. What are the real risks and how common are they. And then the specific thing I want you to know as an emergency physician, because it is my world and it is being badly undercommunicated.
What these drugs actually are
We have to start with some physiology, because not all GLP-1s are created equal and the differences matter when you are reading about them online.
GLP-1 stands for glucagon-like peptide, and it is a hormone your gut already makes when you eat. It has many roles in the body. Broadly speaking, when food enters the small intestine, GLP-1 is released into the bloodstream and acts on the pancreas, on gastric emptying, and on the appetite centers in your brain.
GIP, which stands for glucose-dependent insulinotropic polypeptide, is a second normal gut hormone. It activates GIP receptors to help control blood sugar by releasing insulin after eating, and it also helps manage appetite.
There are two broad drug categories worth knowing. First, the GLP-1 receptor agonists. That includes the semaglutide medications (Wegovy, Ozempic and Rybelsus), dulaglutide (Trulicity), and the oral agent orforglipron (Foundayo). Then you have the dual GIP and GLP-1 receptor agonists, which is tirzepatide (Mounjaro and Zepbound).
All of these drugs mimic the hormones your body already makes. They tell your pancreas to release insulin when your blood sugar rises, they slow down how fast your stomach empties, and they act on the appetite centers in your brain. That combination is why people feel full sooner, stay full longer, and eat less without having to white-knuckle their way through it.
One historical detail is worth holding onto, because it reframes everything that follows. These drugs were built for type 2 diabetes. The weight loss came about as, shall we say, a happy side effect.
Question one: what is the actual benefit?
The evidence here is genuinely striking, and it is easiest to understand if you split it by condition rather than treating these as weight loss drugs and stopping there.
Start with diabetes, because that is the condition these drugs were designed to manage. There is a good narrative review that covers most of the diabetes trials, and there are a lot of them.¹ One in particular is the SUSTAIN 3 trial, which compared semaglutide against exenatide in people with type 2 diabetes. It found a mean reduction in HbA1c of 1.5% versus 0.9% in the exenatide group, a statistically significant difference.²
Then the heart. In a randomized trial of 17,604 people who had existing cardiovascular disease and were overweight or obese, but who did not have diabetes, weekly semaglutide reduced the rate of cardiovascular death, heart attack or stroke to 6.5%, compared with 8.0% on placebo, over roughly three years of follow-up.³
And then the one everybody knows about, which is weight. The SURMOUNT-1 trial, a randomized trial of once-weekly tirzepatide, showed a mean weight loss of around 15% at the lowest dose after 72 weeks, rising to roughly 21% at the highest dose.⁴ That is approaching surgical weight-loss territory.
Sit with that for a second, because it reframes the whole conversation. These drugs started out as a treatment for diabetes. What we ended up with is a class that produces meaningful weight loss, improves glycemic control, and reduces the risk of heart attack and stroke in people who do not have diabetes at all. So whatever you think about the culture that has grown up around these drugs, and there is plenty to think about, the clinical case is not built on vanity. It is built on cardiovascular, diabetes and weight outcomes.
Question two: what are the real risks?
The most common side effects by far are gastrointestinal. Nausea, vomiting, diarrhea and constipation. For most people these are worse when starting the drug or increasing the dose, and they tend to settle.
But they are not trivial, and I want to give you a number rather than a reassurance. In that same cardiovascular trial, adverse events led 16.6% of people on semaglutide to stop the drug permanently, compared with 8.2% on placebo.³ That is roughly one in six people discontinuing because of side effects, mostly gastrointestinal ones. If you think back to the patient in my opening case and how horrible they felt, you can understand exactly how that happens. So anyone selling these drugs as effortless is not being honest with you.
There are rarer but more serious concerns your doctor will screen for, including pancreatitis and gallbladder problems, along with specific situations where these drugs should not be used at all, such as a personal or family history of a particular type of thyroid cancer. That is a conversation to have with your prescriber, not with a comment section.
The part I actually worry about
Here is the one consideration I want to spend real time on, because it sits squarely in my world.
One of the most powerful actions of these drugs is slowing gastric emptying. That is not a side effect. It is the mechanism, and it is part of why they work. It is also the reason my patient turned up vomiting.
But it means something else that almost nobody mentions. When you are told to fast before a procedure, your stomach may not actually be empty the way everyone assumes.
In a study that used ultrasound to look directly into people's stomachs before elective surgery, 40% of patients who had taken semaglutide within 10 days had increased residual gastric content, compared with just 3% of patients who had not taken it. That was despite following standard fasting guidelines exactly as instructed.⁵
Why does this matter? If there is still food and gastric contents sitting in your stomach when you go under anesthesia, it can come back up and go into your lungs. We call that aspiration, and it is a serious complication that can rarely be fatal.
To be clear, and this is important, in that gastric ultrasound study there were no actual cases of aspiration.⁵ So this is a risk signal, not a body count, and I do not want to frighten you off a drug that may be doing you a great deal of good.
What I want is simple. Tell every single person on your care team that you are taking one of these drugs. Your surgeon, your anesthetist, your dentist, your endoscopist, and me, if you ever land in my department. Do not assume it is already in the chart. They can adjust your fasting plan, change the anesthetic approach, or scan your stomach before they start.
The things that determine whether this works for you
Muscle loss is a real consideration
When you are losing weight rapidly on fewer calories, you lose muscle along with fat. That is why protein intake and resistance training are not optional extras. They are part of doing this properly.
Obesity management guidelines strongly advocate a multidisciplinary team approach, precisely because weight management is not just a prescription.⁶ In practice that means protein supplementation can be helpful for some people, alongside working with a trainer or an exercise physiologist so your body is getting the stimulus it needs to hold onto muscle mass. And honestly, that should be the standard foundation for every human, drug or no drug.
Fiber quietly disappears
While we are on the subject of reduced intake, you are also at risk of your fiber intake dropping. Anyone who has tried to deliberately increase their fiber knows the feeling of fullness that comes with those foods. When you are already experiencing slowed gastric emptying from the medication, fiber is often the first thing to go.
This is a situation where a fiber supplement can make sense for some people, alongside paying attention to the fiber content of the foods you do still eat.
When you stop, the weight tends to come back
This one gets weaponized, so let us handle it properly.
The STEP 4 trial showed the effect clearly. In this randomized trial of adults with overweight or obesity, 803 participants completed a 20-week run-in of weekly subcutaneous semaglutide at 2.4 mg and had a mean weight loss of 10.6%. They were then randomized to continue semaglutide or switch to placebo for another 48 weeks. At the end of that period, the continued-treatment group had a mean weight change of negative 7.9%, compared with a weight gain of 6.9% in the placebo group.⁷
Now, before you comment see, you just regain the weight if you stop taking these drugs, understand that you get the exact same effect if you lose weight through diet and exercise and then stop the diet. A systematic review and meta-analysis found this, and other work has shown that the hormones controlling appetite stay altered long after a diet ends.⁸˒⁹
What that tells you is not that the drugs fail. It tells you this is a long-term treatment for a chronic condition, not a short course, and that behavioral support matters enormously either way.
Compounded and grey-market versions
Now for my anecdote, which is exactly what it is. Every patient I have personally seen in the situation of my opening case was using a compounded version of these drugs.
Therein lies the genuine hazard, because dosing errors with these medications land people in emergency departments. The patient in my case was managed with an algorithmic approach, often driven by automated decisions rather than a clinician who had examined them.
When companies like this appear, I would recommend caution, because weight loss and the management of chronic medical conditions should involve a multidisciplinary approach. Many boutique operators in this space simply are not doing that.
How Should This Modify Your Practice?
For patients and caregivers
If you take one thing from this article, take this one. Tell every clinician you meet that you are on a GLP-1, especially before any procedure. Surgeon, anesthetist, dentist, endoscopist, emergency physician. Do not assume it is in the chart.
Beyond that, the benefit here is real and it extends well past weight loss, with a demonstrated reduction in heart attacks and strokes. The most common side effects are gastrointestinal, and in one large trial roughly one in six people stopped the drug because of them. The rarer risks are worth a proper conversation with your prescriber.
If side effects are making this intolerable, that is not the end of the road. Work with your doctor on adjusting the dose or switching to a different agent in the class. A different drug or a different dose may give you the benefit with far fewer side effects. What you should not do is let an app titrate you upward without anyone asking how you are actually feeling.
I see these drugs as a Tier 2 tool, and a genuinely good one for the right person. But they sit on top of the foundations, never in place of them. Diet, exercise, sleep, stress management, and a primary care doctor who knows you. Protein, fiber and resistance training matter more on these drugs, not less. The doctor who knows your history is the person who can help you decide whether this is right for you, monitor you properly, and keep you safe while you are on it. That is not gatekeeping or a formality. For these drugs, it is the whole ballgame.
For clinicians and trainees
The peri-procedural question is the one to change practice on. Ask about GLP-1 use explicitly rather than relying on the medication list, because a substantial share of these prescriptions now come through telehealth and compounding channels that may never reach the primary record. The gastric ultrasound data give you a defensible reason to ask, and to consider point-of-care gastric ultrasound or an adjusted fasting plan in the patients who say yes.⁵
In the emergency department specifically, protracted vomiting in a patient on a GLP-1 deserves a dose history rather than a reflexive antiemetic and discharge. Ask when the last injection was, whether the dose recently changed, and who directed that change. Recent escalation is the detail that most often explains the presentation, and it is the detail patients rarely volunteer because they do not know it is relevant.
On counseling, the discontinuation figure is more useful than a general warning about nausea. Telling a patient that roughly one in six people in a large trial stopped the drug because of adverse effects sets an honest expectation and makes it likelier they come back to discuss dose adjustment rather than quietly stopping.
And the framing worth passing to patients is that this is chronic disease management. The weight-regain data are not an indictment of the drug, they are the same physiology we see after any successful diet, with appetite-regulating hormones remaining altered long after the intervention ends.⁸˒⁹ Framed that way, the conversation shifts from did it work to what does long-term management look like.
About the author
Dr. Adrian Cois, MD is an Emergency Medicine physician and Assistant Professor. He hosts Overheard in the Emergency Room, a podcast and YouTube series translating the evidence behind everyday health decisions into something you can actually use.
Disclosure: Dr. Cois has no financial relationship with any pharmaceutical company, telehealth provider, compounding pharmacy, supplement manufacturer or product mentioned in this episode or article. No affiliate links are used on this site.
Related reading
● The medication framework episode, S2E3 (18), which is the hub for this cluster and the lens used throughout this article. Watch it first.
● S2E5 (20), Your Cholesterol Numbers Explained, for how to read the lab work that often comes alongside these prescriptions.
● Food, NAFLD and the 80/20 Plate (Season 1, Episode 2), on the dietary foundations that matter more on these drugs, not less.
● Your Ultimate Supplement Guide (Season 1, Episode 14), before you buy the protein or fiber supplement.
● Blood Pressure, Cholesterol and Avoiding the Cath Lab (Season 1, Episode 7), on the cardiovascular risk picture these drugs are now part of.
References
AMA style. All nine verified against PubMed on August 31, 2026. Reference 3 restored to full citation form, reference 8 given its journal, and reference 2 corrected to the 2018 volume.
1. Alfaris N, Waldrop S, Johnson V, Boaventura B, Kendrick K, Stanford FC. GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review. eClinicalMedicine. 2024;75:102782. doi:10.1016/j.eclinm.2024.102782
2. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018;41(2):258-266. doi:10.2337/dc17-0417
3. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
4. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
5. Nersessian RSF, da Silva LM, Carvalho MAS, et al. Relationship between residual gastric content and peri-operative semaglutide use assessed by gastric ultrasound: a prospective observational study. Anaesthesia. 2024;79(12):1317-1324. doi:10.1111/anae.16454
6. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. Circulation. 2014;129(25 Suppl 2):S102-S138. doi:10.1161/01.cir.0000437739.71477.ee
7. Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224
8. Hartmann-Boyce J, Theodoulou A, Oke JL, et al. Association between characteristics of behavioural weight loss programmes and weight change after programme end: systematic review and meta-analysis. BMJ. 2021;374:n1840. doi:10.1136/bmj.n1840
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