Weight Loss Drugs And Tummy Issues

Medically reviewed by Riaz S. Chowdhury, MD, PhD, AGAF, FACG

In recent decades, Glucagon-like Peptide-1 (GLP-1) agonists have gained popularity in the fight against obesity. GLP-1 is a hormone naturally produced in the body, specifically in the cells of the small intestine and colon. These medications include semaglutide (found in Ozempic and Wegovy) and liraglutide (used in Saxenda).

Data analyzed by Epic Research revealed a 40-fold increase in these drugs between 2017 and 2021. This surge indicates a significant shift in treatment patterns, with an estimated six million Americans now reliant on these medications. Various factors contribute to this dramatic rise, including increased awareness of health conditions, increased prescribing practices among providers and societal acceptance of medication as a viable treatment option. Additionally, advancements in drug formulation and marketing strategies have played a role in making these therapies more accessible. 

This evolving health care dynamic underscores the need for better understanding of patient needs and the development of comprehensive strategies to promote responsible use of these medications.

Where do GLP-1 agonists naturally occur in the body?

GLP-1 agonists act on receptors located throughout the body. These receptors are abundant in the pancreas, stomach, intestines, liver, brain, heart muscles and other muscles. This widespread distribution means that GLP-1 agonists can influence numerous bodily functions.

How can this medication be taken?

GLP-1 agonists can be administered either orally with a daily dosage or through a weekly subcutaneous injection.

How does obesity work in cooperation with GLP-1 agonists?

Multifactorial Nature of Obesity

Obesity occurs through a multifactorial mechanism, meaning it has various contributing factors. This explains why GLP-1 agonists can't eliminate obesity. Effective management requires comprehensive lifestyle modifications, such as diet and nutrition as well as addressing underlying medical conditions.

Contributing Factors for Obesity:

• Central nervous system issues (20%): Twenty percent of patients with obesity using GLP-1 agonists still eat more due to satiety problems rooted in the central nervous system.
• Psychological and behavioral challenges (19%): Nine percent of people face psychological and behavioral challenges related to food.
• Altered vagal activity (17%): Seventeen percent of patients have altered vagal activity, including heart rate, blood pressure, inflammation, relaxation, attentiveness and engaged facial expressions and vocalizations.
• Gastric Distention (14%):Fourteen percent of patients experience gastric swelling and need larger meals to feel full.
• GLP-Related Issues (10%): Only 10 percent of patients have direct GLP-related issues.

Mechanism of Action of GLP-1 agonist:

• Appetite Reduction: GLP-1 agonists act through the central nervous system (hypothalamus) to decrease appetite. This can help 20 percent of patients with eating issues linked to the central nervous system.
• Gastric Emptying & Satiety (25%): Twenty five percent of patients with gastric emptying problems benefit from GLP-1 agonists, as the drugs are found to slow down the stomach globally.
• Gastroparesis: These medications slow down stomach function, making patients feel full. When combined with central nervous system effects, this aids in reducing obesity.

What are the side-effects of these drugs?

Gastrointestinal Side-Effects:

• Prevalence: About one-third of patients develop gastrointestinal side-effects, lasting from two days to up to 60 days.
• Timing: Side-effects can arise at any time but often within the first week of treatment.

Common Side-Effects:

• Nausea, vomiting and altered bowel habits: Over one-third of patients will experience nausea, vomiting and altered bowel habits.
• Constipation: This is the most common side-effect.
• Diarrhea: This side-effect is less common but possible.

Physiologic Effects:

• Gastroparesis: Nausea, vomiting and constipation usually start within the first week. They result from the inhibition of stomach function (gastroparesis), causing fluid and food build-up in the stomach and small bowel.
• Intestinal motility: GLP-1 agonists also inhibit small and large intestine motility, leading to constipation.
• Rarely, some patients develop acute pancreatitis.
• Evidence has shown an increase in the number of gallstone formations.

Is anyone not recommended to take GLP-1 medications?

Some people are recommended never to start on GLP-1 medications. 

These include patients with the following histories or medical conditions:

• History of thyroid cancer or family history of the thyroid or other endocrine tumor 
• Pregnancy
• Severe renal impairment, such as kidney malfunction
   

What treatments are available for these side-effects?

• Patients should start on a low dosage and progress slowly. Beginning with the lowest possible dose allows the body to adjust.
• Increase incrementally: The dosage should be gradually increased based on the health care provider's recommendations. This helps reduce the intensity of side-effects.
• Dietary modifications
  • Patients should eat small, frequent meals: Eating smaller portions more frequently can help control nausea.
  • Avoid fatty and greasy foods: These can exacerbate gastrointestinal symptoms. Opt for lean proteins and fiber-rich foods.
  • Consume mild flavors: Users should stick to bland foods that are less likely to irritate the stomach, such as toast, rice and bananas.
• Hydration
  • Stay hydrated: Drinking plenty of fluids, especially water, helps avoid dehydration from vomiting or diarrhea.
  • Avoid caffeine and alcohol: These can further irritate the stomach and contribute to dehydration.
• Eating Habits
  • Eat slowly: It is important to take time while eating to prevent overloading the digestive system.

Are GLP-1 drugs mostly safe?

GLP-1 drugs are generally safe but do come with some side-effects. Roughly eight to nine percent of patients may need to discontinue use due to preexisting conditions. Despite this, GLP-1s play a crucial role in managing obesity, which is far from a cosmetic issue. Obesity can lead to high cholesterol, diabetes, fatty liver disease, coronary artery disease, stroke and joint problems, often resulting in joint replacements and liver transplants. 

Gastrointestinal side-effects from GLP-1s are common but manageable, making these drugs essential for obesity management.

Are GLP-1s lifelong drugs?

The duration of GLP-1 treatment depends on its indication. For obesity, these drugs likely need to be taken indefinitely. Obesity is a complex issue requiring a multifaceted approach, including GLP-1s and lifestyle modifications.

Can patients schedule directly with your office if they are on GLP-1s and experiencing side-effects?

Yes, patients can self-refer to WakeMed Gastroenterology, though most often they come through a primary care referral. If side-effects do not improve after a few days, or if there are suspicions of acute pancreatitis, patients are either referred to us or hospitalized based on the severity of their symptoms.

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About Riaz S. Chowdhury, MD, PhD, AGAF, FACG

Dr. Riaz Chowdhury is board certified in gastroenterology and internal medicine, joining WakeMed Physician Practices - Gastroenterology after working with Piedmont Gastroenterology Specialists in Winston-Salem since 2004.

His special interests include pancreaticobiliary disease such as common bile duct stones, pancreatic cancer and chronic pancreatitis. His expertise includes Endoscopic Retrograde Cholangiopancreatography (ERCP), spyglass cholangioscopy and endoscopic ultrasonography with fine needle aspiration and celiac plexas block, among others.

He earned his medical degree at Dhaka University in Bangladesh, and his doctorate in gastroenterology from Okayama University Medical School in Okayama, Japan. He completed residency training in internal medicine at the University of Maryland at Harbor Hospital Center in Baltimore, and a fellowship in gastroenterology and therapeutic endoscopy at the University of Florida in Gainesville, FL.

Dr. Chowdhury is a member of the American Society for Gastroenterological Endoscopy, American Gastroenterological Association, American College of Gastroenterology, American Pancreatic Association and North Carolina Society of Gastroenterology. He has served on several boards and committees at D.L. Davis Forsyth Regional Cancer Center. He is widely published and has had 16 original articles published in various national and international journals. He has been awarded the Fellowship of American Gastroenterology Association (AGA).