The Remarkable Rise of GLP-1 Agonists
In recent years, the names Ozempic and Wegovy, both formulations of the drug semaglutide, have become household names. Originally approved for treating type 2 diabetes (as Ozempic) and later for chronic weight management (as Wegovy), these drugs belong to a class of medications called GLP-1 receptor agonists. They’ve delivered remarkable results, helping millions manage blood sugar and achieve significant weight loss.
With their popularity has come a wave of discussion about their side effects. Some are well-established and expected by doctors, others remain speculative, and a few have been amplified by social media trends. For patients and healthcare providers, it’s important to separate what’s medically proven from what’s simply hype.
How Semaglutide Works
To understand the side effects, you first have to understand how the drug works. Semaglutide mimics a natural gut hormone called GLP-1 (glucagon-like peptide-1). After you eat, this hormone is released, sending several key signals throughout your body. [1]
- Increases Insulin Release: GLP-1 signals the pancreas to release insulin, which helps lower blood sugar.
- Slows Digestion: It slows down the rate at which food leaves the stomach, a process known as gastric emptying. This helps you feel fuller for longer.
- Reduces Appetite: GLP-1 travels to the brain’s appetite centers, reducing hunger and cravings. [2]
It’s these very mechanisms, especially the slowing of digestion, that are responsible for both the drug’s therapeutic benefits and its most common side effects.
The Proven Side Effects Doctors Expect
The majority of side effects are predictable, manageable, and often decrease over time. Doctors are well-prepared for these issues and address them through careful patient management.
A. Gastrointestinal (GI) Discomfort
This is, by far, the most common class of side effects. Clinical trials show that a significant portion of users experience these issues, especially when they first start the medication or when the dose is increased. [3]
- Nausea and Vomiting: Up to 30% of users in clinical trials reported nausea, and around 10% experienced vomiting.
- Diarrhea and Constipation: These two opposing issues are also very common, with some users reporting one and others the opposite.
- Abdominal Pain and Bloating: Feelings of fullness, pain, and gas are also frequently reported due to the slowed gastric emptying.
Doctors mitigate these effects by starting with a low dose and gradually titrating (increasing) the dosage over weeks or months. This allows the body to slowly adjust to the medication, which can significantly reduce or eliminate GI discomfort. [4]
B. Hypoglycemia (Low Blood Sugar)
While semaglutide alone rarely causes dangerously low blood sugar in people without diabetes, the risk increases when it’s combined with other diabetes medications, particularly insulin or sulfonylureas. [5] Doctors are highly watchful for this and often adjust the dosages of these other medications to prevent hypoglycemia.
C. Other Frequent Issues
While less talked about than the GI issues, several other common, but usually mild, side effects can occur. These include headaches, fatigue, dizziness, and injection site reactions (such as redness or itching). Like GI issues, these tend to be temporary and resolve as the body adapts to the medication. [6]
Rare but Serious Side Effects
These side effects are what doctors truly monitor for. While their incidence is low, they require immediate medical attention if symptoms appear.
A. Pancreatitis and Gallbladder Problems
There have been rare reports of pancreatitis (inflammation of the pancreas) and gallbladder inflammation or gallstones in users of GLP-1 agonists. While a definitive, causal link has not been confirmed in large-scale studies, the risk is a major concern. The mechanism for gallbladder issues is often linked to the rapid weight loss itself, which can increase the risk of gallstone formation.
- Red Flags: Doctors advise patients to seek immediate care if they experience severe, persistent abdominal pain that may radiate to the back, with or without vomiting.
B. Thyroid Cancer Risk
Semaglutide carries a boxed warning, the FDA’s most serious warning, regarding the risk of thyroid tumors. This warning is based on animal studies in which rats developed thyroid tumors after receiving the medication. [8] The risk in humans, however, is not yet clear. For this reason, doctors will not prescribe the medication to anyone with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
C. Kidney Injury and Allergic Reactions
Although rare, cases of acute kidney injury have been reported. This can be an indirect effect, as severe vomiting and diarrhea from GI side effects can lead to dehydration and, subsequently, kidney issues. [9] Additionally, severe allergic reactions, though rare, are a possibility. Patients are advised to be vigilant for symptoms like swelling of the face, lips, tongue, or throat, which require immediate emergency care.
D. Eye Concerns
This is an area of growing research and concern.
- Diabetic Retinopathy: Patients with pre-existing diabetes who use semaglutide may face a higher risk of worsening diabetic retinopathy, a condition that can damage blood vessels in the retina. [10]
- NAION (Non-arteritic anterior ischemic optic neuropathy): Often referred to as an “eye stroke,” NAION is a rare but serious condition that can cause sudden vision loss. Two studies suggest a very small increase in risk for NAION among GLP-1 agonist users. The absolute risk remains very low, but doctors are now more alert to symptoms like sudden, painless vision loss in one eye.
The Speculative and Hyped Effects
While common and rare side effects are well-documented in clinical literature, a different class of risks has emerged on social media and in news headlines.
A. “Ozempic Face”
This term, coined on social media, refers to skin sagging or hollow cheeks that can occur during rapid weight loss. Dermatologists and plastic surgeons widely agree that this is not a direct effect of the drug itself, but rather a normal consequence of losing a significant amount of fat from the face. [12] The rapid pace of weight loss with semaglutide can make this effect more pronounced than with slower, traditional weight loss.
B. “Ozempic Teeth”
Reports of tooth decay, gum issues, and dry mouth have surfaced online, but these claims are currently anecdotal and lack strong scientific backing. The likely culprit is the indirect effect of the drug. For instance, severe vomiting can expose teeth to stomach acid, while some people might reduce their fluid intake due to nausea, leading to a dry mouth that increases the risk of tooth decay. [13]
How Doctors Reduce and Manage Risks
The key to safe and effective use of these drugs is proper medical supervision. A doctor’s role goes far beyond writing a prescription.
- Gradual Dose Titration: As mentioned, starting with a low dose and increasing it slowly is the primary method for reducing GI side effects and helping the body adapt.
- Regular Monitoring and Lab Workups: Doctors will often order lab tests to monitor kidney function, liver health, and blood sugar. They also perform a full medical history to check for family history of thyroid or pancreatic issues.
- Ophthalmology Checks: For patients with diabetes or those who report any visual changes, a referral to an ophthalmologist is crucial.
- Lifestyle Counseling: Doctors and dietitians work with patients to ensure they are maintaining proper nutrition and hydration, which can help mitigate many of the side effects and support sustainable weight loss.
