Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized the treatment of type 2 diabetes and obesity by effectively controlling blood sugar and promoting significant weight loss. These medications mimic a natural gut hormone to regulate appetite and slow gastric emptying. However, their increasing popularity has brought widespread attention to their potential side effects. Understanding how many people experience adverse effects and which ones are most common is crucial for both patients and healthcare providers when starting or continuing therapy.
How Many People Experience GLP-1 Side Effects?
Real-world data and clinical trial results consistently show that a substantial portion of patients experience side effects from GLP-1 agonists. Estimates for gastrointestinal (GI) adverse events, which are the most common, range from 40% to 70% of treated patients. For instance, a RAND survey in August 2025 found that about half of adult GLP-1 users reported experiencing nausea, and approximately one-third reported diarrhea. Clinical trial data for specific medications, such as the liraglutide pivotal trial, reported that over 80% of participants experienced adverse events overall, compared to 63.3% on placebo, with the majority being GI-related.
It is important to note that most of these side effects are mild or moderate in severity and tend to be dose-dependent, meaning they are more pronounced when a person first starts the medication or has their dose increased. As the body adjusts to the drug, these symptoms often subside, typically clearing up within one to two months.
Common Gastrointestinal Side Effects
Gastrointestinal issues are the most prevalent class of side effects associated with GLP-1 agonists. The following are commonly reported in clinical trials and post-marketing surveillance:
- Nausea: Frequently cited as the most common side effect, with some studies showing rates affecting up to 50% of patients. It is often highest in the first few weeks of treatment and decreases over time.
- Diarrhea: Also a very common effect, with percentages ranging from about 20% to over 30% depending on the specific medication and study.
- Vomiting: Affects a smaller proportion of patients compared to nausea, with figures typically around 15–25% in various trials.
- Constipation: Reported by a notable percentage of users, often around 20%.
- Abdominal pain/discomfort: Experienced by many patients, with percentages varying. One real-world analysis found abdominal pain to be the most common GI event, affecting 57.6% of participants in a specific cohort.
Less Common and Serious Side Effects
While most side effects are manageable, some rare but serious events have been reported. It is crucial to be aware of these, though their overall incidence is very low.
- Pancreatitis: Inflammation of the pancreas has been reported, with some studies suggesting an increased risk, though the overall incidence is typically less than 1%. Some observational studies have found signal associations, but clinical trials and recent meta-analyses have often failed to show a significant increase in risk compared to controls.
- Gastroparesis (Stomach Paralysis): Due to the delayed gastric emptying effect, some patients may experience a more severe slowing of stomach motility. While the risk of developing gastroparesis is higher with GLP-1 use, the overall prevalence is low.
- Gallbladder-related disorders: Increased risk of gallbladder and biliary disorders has been observed, particularly in patients experiencing rapid weight loss. A systematic review found that GLP-1 therapy elevated the probability of these issues (pooled relative risk, 1.37).
- Injection site reactions: Localized reactions such as redness, itching, or bruising can occur but are generally transient.
- Thyroid C-cell tumors: Long-term studies in rodents have shown an increased risk of these tumors, leading to a Boxed Warning on product labels for some medications. However, the risk in humans is unknown, and the drugs are contraindicated in patients with a history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.
Discontinuation Rates and Side Effects
Despite the mild-to-moderate nature of most side effects, they remain a primary driver of treatment discontinuation. Recent studies have highlighted significant dropout rates, especially among patients using the medication for weight loss rather than diabetes, often due to persistent GI discomfort.
- High Discontinuation: A 2025 study found that 53.6% of adults prescribed a GLP-1 for overweight or obesity ended therapy within one year, and 72.2% stopped within two years.
- Impact of GI Events: Experiencing moderate or severe GI side effects was significantly associated with higher rates of discontinuation.
- Role of Cost: Insurance coverage issues and high out-of-pocket costs also contribute to the high discontinuation rates.
Comparison of Side Effects Among GLP-1 Medications
The side effect profile can vary somewhat between different GLP-1 agonists, influencing patient tolerability and physician prescribing decisions. The table below compares the reported rates of common adverse events for a few widely used GLP-1 and dual GLP-1/GIP receptor agonist drugs based on clinical trial and real-world data.
| Side Effect | Liraglutide (3.0 mg) | Semaglutide (2.4 mg) | Tirzepatide (15 mg) |
|---|---|---|---|
| Nausea | 40.2% | 44.2% | 31.0% |
| Diarrhea | 20.9% | 31.5% | 23.0% |
| Constipation | 20.0% | 23.4% | 11.7% |
| Vomiting | 16.3% | 24.8% | 12.2% |
| Decreased Appetite | 10.8% | N/A | 8.6% |
| Any Serious AE | 6.2% | 9.8% | 5.1% |
Note: Percentages derived from specific clinical trial data and comparisons should be interpreted with caution, as study populations and designs vary.
Managing Common Side Effects for Better Adherence
For most patients, managing GLP-1 side effects is possible with a few adjustments. A “start low, go slow” approach, involving a gradual increase in dosage, is a key strategy used by healthcare providers to help the body acclimate.
- Eat Small, Frequent Meals: Smaller portions put less stress on the digestive system, which is operating more slowly.
- Avoid Trigger Foods: Reducing intake of fatty, greasy, and spicy foods can help alleviate nausea and upset stomach.
- Stay Hydrated: Drinking plenty of water is essential, especially with diarrhea or vomiting, and can also help with constipation.
- Incorporate Fiber: For constipation, a gradual increase in dietary fiber and adequate water intake is recommended.
- OTC Remedies: Over-the-counter options like ginger or peppermint for nausea and fiber supplements can offer additional relief.
- Consult a Healthcare Provider: Always discuss side effect management with a doctor, who may adjust the dosage or recommend a different medication.
Conclusion: Understanding the Full Picture
The percentage of people who have side effects from GLP-1 agonists is significant, with most experiencing mild to moderate gastrointestinal issues, particularly early in treatment. While these side effects can be a source of discomfort and lead to discontinuation for many, they are often manageable with the right strategies, including careful dosing and dietary modifications. Rare but more serious adverse events like pancreatitis and gallbladder issues occur in a very small portion of users. Given the powerful therapeutic benefits of GLP-1 medications, open communication with a healthcare provider is vital to weigh the risks and rewards, address potential side effects effectively, and ensure long-term treatment adherence. For more information, please visit the official National Institutes of Health website at https://pmc.ncbi.nlm.nih.gov/.
