For the last several decades, obesity has been a growing problem in the United States. Recent data indicates that over 40% of Americans are obese and more than 30% are overweight. Over this same period, the commercial weight loss industry has ballooned to $38 billion without making much of an impact on these numbers. A development that has the potential to change this dynamic is the arrival of GLP-1 receptor agonist medications like semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro). These medications have demonstrated remarkable effectiveness in helping people achieve significant weight loss, but they come with some potential side effects that can significantly impact the digestive system and affect quality of life.1

How Do GLP-1 Medications Work?

GLP-1 (glucagon-like peptide-1) is a hormone that your body naturally produces in the gut when you eat. This hormone plays several important roles in regulating metabolism, including stimulating insulin release, reducing glucagon secretion, and signaling feelings of fullness to the brain. GLP-1 receptor agonist medications like semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro) work by mimicking this natural hormone, though at higher and more sustained levels than the body would produce on its own.

These medications were originally developed to treat type 2 diabetes because of their ability to improve blood sugar control. When researchers observed that patients taking these drugs also experienced significant weight loss, pharmaceutical companies began developing higher-dose formulations specifically for weight management. The medications are typically administered as weekly injections, though some oral formulations exist. Clinical trials have shown that patients can lose 15-20% of their body weight on average, making these among the most effective weight-loss medications ever developed.

Why GLP-1 Medications Affect the Digestive System

The connection between GLP-1 medications and digestive symptoms stems directly from how these drugs alter normal gut function. The primary mechanism involves delayed gastric emptying, which means the stomach releases food into the small intestine much more slowly than it would naturally. This slowing effect is intentional and beneficial for weight loss, as it creates prolonged feelings of fullness and prevents rapid spikes in blood sugar after meals. However, when food remains in the stomach longer than usual, it can create physical discomfort and trigger various digestive symptoms.

GLP-1 receptors exist throughout the digestive tract, not just in the stomach. When medications activate these receptors, they influence multiple aspects of gut function simultaneously. The drugs slow the muscular contractions that move food through the digestive system, reduce stomach acid secretion, and alter the signals sent between the gut and brain. These widespread effects explain why digestive side effects are so common with GLP-1 medications. Most patients experience changes in how their digestive system operates, though the severity varies widely.

The delayed stomach emptying creates what some doctors describe as an artificial feeling similar to having eaten a very large meal. Your stomach is holding onto food longer, creating sustained pressure and fullness. For many patients, this translates to nausea, particularly in the early weeks of treatment or when doses are increased. The slowed motility can also lead to bloating, constipation in some patients, or paradoxically diarrhea in others as the intestines adjust to altered food transit. Heartburn and acid reflux can worsen because stomach acid has more time to irritate the esophagus when the stomach empties slowly. These effects are typically most noticeable during the first several weeks, though some degree of altered digestion persists throughout treatment.2

Common Gastrointestinal Side Effects

Digestive side effects are extremely common with GLP-1 medications, affecting anywhere from 30% to 80% of patients depending on the specific drug and dosage. These symptoms are typically mild to moderate in intensity and tend to be most pronounced during the first few weeks of treatment or when doses are increased. For many patients, the digestive discomfort gradually improves as the body adjusts to the medication, though the timeline varies considerably from person to person.

  • Nausea: Nausea is the most common complaint among patients taking GLP-1 medications, and higher doses tend to make the nausea more pronounced. Most patients find that nausea improves significantly after the first month or two as their body adapts. Eating smaller, bland meals and avoiding lying down immediately after injections can help manage this symptom.
  • Vomiting: Vomiting can occur when patients eat too much or too quickly while their stomach is emptying slowly. Starting with low doses and increasing gradually helps reduce the likelihood of this problem. Persistent or severe vomiting, or inability to tolerate fluids, requires medical attention due to dehydration risk.
  • Diarrhea: Intestinal transit can become irregular or accelerated in some patients, leading to diarrhea that is typically mild to moderate and temporary. This may alternate with constipation as the digestive system adjusts. Staying hydrated and maintaining a plain diet generally helps, but severe or persistent diarrhea warrants medical consultation.
  • Constipation and bloating: Slowed gut motility can lead to less frequent bowel movements and persistent feelings of fullness or bloating. Adequate fiber and fluid intake can help, though finding the right balance can be challenging when also dealing with nausea. Some patients benefit from fiber supplements or stool softeners under medical guidance.
  • Heartburn and reflux: Food and stomach acid remaining in the stomach longer can worsen acid reflux symptoms. Studies suggest these medications can increase the risk of GERD symptoms. Using antacids or acid reducers as recommended and avoiding lying down after meals can help manage these symptoms.

Digestive Health Care from Cary Gastro

GLP-1 medications have the potential to be a life-changing weight management intervention for many people, but their digestive side effects can be burdensome. Whether you’re experiencing GI symptoms from these medications or dealing with other digestive concerns, the physicians at Cary Gastroenterology specialize in diagnosing and treating a wide range of digestive conditions. Our team can help evaluate your symptoms and develop treatment approaches tailored to your specific needs. Contact us today to request an appointment and learn more about how we can support your digestive health.


1https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity
2https://pmc.ncbi.nlm.nih.gov/articles/PMC9821052/