GLP-1 Medications: What You Need to Know About Side Effects
Summary
GLP-1 medications like Ozempic and Wegovy offer powerful benefits for weight loss and diabetes management—but they’re not risk-free. Gastrointestinal side effects are the most common issue, while concerns around pancreatitis, gallbladder disease, thyroid tumors, and mental health remain under investigation. The evidence doesn’t confirm most severe risks, but careful monitoring and patient education are essential to maximize benefit and minimize harm.
GLP-1 receptor agonists—like semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), and their peers—have transformed how we treat type 2 diabetes and obesity. These agents mimic the body’s natural glucagon-like peptide-1 hormone, regulating blood glucose while promoting satiety and weight loss¹.
But as prescriptions skyrocket, so do questions around side effects. From the common (hello, nausea) to the clinically complex (pancreatitis? tumors?), here’s a look at what the evidence actually says.
Gastrointestinal Side Effects: The Frequent Flier
GI issues are the most commonly reported side effects of GLP-1 medications—and they’re not subtle. Nausea, vomiting, diarrhea, constipation, abdominal pain, and bloating show up regularly in trials and real-world use.
In one study, 74.2% of patients on a GLP-1 reported GI symptoms². In another, 6.8% discontinued the medication entirely due to these effects³. While these side effects are typically dose-related and often fade over time, they remain the leading reason for early drop-out from clinical trials.
Pancreatitis: Coincidence or Concern?
Reports of pancreatitis have surfaced in GLP-1 users, but it’s not clear if the drug is the culprit—or if diabetes itself is to blame. People with type 2 diabetes have an 84% higher baseline risk of developing pancreatitis compared to the general population⁴.
In controlled trials, pancreatitis rates in GLP-1 groups ranged from 0.1% to 1.2%, with placebo groups reporting similar numbers³ ⁵. Translation? No statistically significant link, but still worth monitoring, especially in symptomatic patients.
Gallbladder and Biliary Effects: A Murky Link
GLP-1s slow gastric emptying, which helps with satiety—but may also play a role in gallbladder issues. The connection isn’t clear-cut: one trial found 2.8% of semaglutide users developed gallbladder disorders vs. 2.3% in the placebo group⁶. That’s a slight bump, but not enough for a definitive cause-and-effect conclusion. More research is needed.
Thyroid Tumors: Rodent Risk, Human Precaution
In animal studies, GLP-1s have been linked to C-cell tumors of the thyroid, including medullary thyroid carcinoma (MTC). While these results haven’t been replicated in human trials, a boxed warning exists. GLP-1s should be avoided in anyone with a personal or family history of MTC or MEN2 (Multiple Endocrine Neoplasia Type 2)⁹.
Side Bar 1: ⚠️ Boxed Warning: Thyroid Tumor Risk
GLP-1 receptor agonists carry a boxed warning (also known as a black box warning) for the potential risk of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC). This caution is based on findings from animal studies and limited human case reports. These medications are not recommended for patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN2). (10)
Side Bar 2: What is a Boxed Warning?
A boxed warning is the FDA’s strongest safety alert, issued when a drug carries a serious or life-threatening risk. It appears prominently on the drug label to ensure prescribers and patients are aware.
Mental Health: Still Under the Microscope
There’s rising attention on mental health changes—especially depression, anxiety, and suicidal ideation—reported anecdotally by some GLP-1 users. One clinical trial showed no increase in suicidality risk⁷, while a retrospective study suggested a twofold increase in mood-related issues⁸. More data is needed. Therefore, clinicians should check in on patients’ mental well-being throughout treatment.
Other Potential Side Effects to Watch
Gastroparesis (stomach paralysis) – Can cause early fullness, bloating, or rare intestinal blockages.
Hypoglycemia – Rare when used alone; more common if paired with insulin or sulfonylureas.
Elevated heart rate – Mild increases noted in some trials.
Vision changes – Includes rare cases of NAION (non-arteritic anterior ischemic optic neuropathy) and nAMD(neovascular age-related macular degeneration).
Side Bar 3: Study finds doubled risk of neovascular age-related macular degeneration with prolonged GLP‑1 use. In late June, a group of people who suffer vision loss after taking Ozempic and Wegovy have requested that their lawsuits be consolidated to a class action in New Jersey state courts.
GLP-1 Agonists: Maximize the Benefits, Minimize the Risks
GLP-1s are among the most powerful tools we have for treating diabetes and obesity—but they're not magic bullets. Gastrointestinal issues top the list of concerns, but gallbladder symptoms, thyroid cancer risks, and mental health questions are all part of the evolving safety profile.
To keep patients safe and outcomes strong, consider the following clinical best practices:
Start low, go slow on dosing
Monitor for GI symptoms, especially early on
Revisit mental health and vision concerns routinely
Avoid use in patients with thyroid cancer history
Stay alert for signs of pancreatitis or gallbladder issues
Smart oversight matters. With proactive monitoring and patient education, the benefits of GLP-1 therapy can far outweigh the risks.
By Anna Watson
PharmD Candidate (P4)
For questions, e-mail pharmd@prodigyrx.com
References:
2 https://www.nejm.org/doi/10.1056/NEJMoa2032183?url_ver=Z39.88 2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
https://www.nejm.org/doi/10.1056/NEJMoa2108269?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15538