Short and Long-term Side Effects of Semaglutide

Semaglutide is an injectable medication used to treat type 2 diabetes and obesity. Semaglutide is marketed as Ozempic, a medication that reduces blood sugar for people with type 2 diabetes and reduces the risk of cardiovascular disease; Rybelsus, an oral form of semaglutide used to treat type 2 diabetes; and Wegovy, a higher semaglutide dose used to treat obesity and overweight when there is also a weight-related medical condition.

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, which means it acts just like the GLP-1 hormone produced in your gut.

Semaglutide has the following effects on your body:

• Stimulates your pancreas to release insulin
• Improves insulin sensitivity
• Blocks your liver from releasing glucose into your bloodstream by decreasing glucagon hormone
• Slows stomach-emptying
• Signals your brain that you are full and satisfied

Boosting GLP-1 levels in your body has many important benefits when you are trying to lose weight or control your blood sugar. Semaglutide works well for weight loss in people with and without diabetes.

However, whenever you change the hormonal balance in your body, it is likely to trigger some unwanted side effects. Many of these side effects are discussed when people post information about their before and after results when taking semaglutide.

Because each person’s metabolism is different, the type, severity, and duration of side effects each person experiences can vary widely.

As with any medication, it is essential to weigh the risks and benefits before taking semaglutide. In many cases, semaglutide side effects diminish over time. Learn more about known semaglutide side effects, what to expect, and tips for managing them.

Allergic Reactions

Severe allergic reactions to semaglutide or any of its components are a rare but potentially serious side effect. Call 911 or get immediate help if you have swelling of your face, tongue, or throat or shortness of breath.

Tell your doctor if you notice itching, redness, or rash at your semaglutide injection site (2).

Constipation

Semaglutide slows stomach emptying and the digestive process. Food and waste move more slowly through the gastrointestinal tract. When waste sits in the colon longer, more water is reabsorbed. This can cause stools to become excessively hard and dry, causing constipation.

Between 11% and 24% of participants in semaglutide clinical trials experienced constipation (3).

Diarrhea

In clinical trials, between 9% and 30% of participants taking semaglutide reported diarrhea. Diarrhea is having loose or watery stools three or more times a day. Semaglutide and other GLP-1 agonists slow stomach emptying.

Semaglutide changes how fast food and waste move through your gastrointestinal tract. If they move too quickly, water is not reabsorbed from waste in the colon, and you can get diarrhea.

Face Changes

One common observation people make when taking Wegovy or Ozempic for weight loss is decreased facial fullness. Fat just under the skin, or subcutaneous fat, supports the skin and provides fullness. When you lose weight rapidly, you may notice facial fat loss. Without support from fat, facial skin may sag and wrinkle because it cannot respond as quickly to fat loss.

Slower weight loss may reduce this effect, but that may run counter to your goal of taking these medications. If you are concerned about changes in your facial appearance, talk to your doctor. They may suggest treatments to restore subcutaneous fat in certain areas of the face (4).

Fatigue

About 11% of people taking Wegovy in clinical trials reported fatigue. Very few people reported fatigue when taking Ozempic.

It is not clear exactly why semaglutide causes fatigue, but some potential explanations include its effect on appetite and energy intake or a response to side effects.

People taking Wegovy for weight loss reported the most fatigue. In clinical trials, they consumed a reduced-calorie diet and took part in an exercise program. Fatigue may result from decreased calorie intake (5, 6).

If you have stressful side effects, such as nausea and diarrhea, this can increase cortisol levels, which can contribute to fatigue. It is important to ensure you are staying well-hydrated and maintaining a healthy electrolyte balance if you have vomiting or diarrhea.

Gallbladder disease

The gallbladder is a sac-like structure under the liver that concentrates and stores bile. Symptoms of gallbladder disease due to inflammation or gallstones include pain in the upper right quadrant of your abdomen, fever, a yellowish tinge to the skin and eyes (jaundice), and clay-colored stools.

Gallbladder disease is not common when taking semaglutide, affecting about 2% of participants in clinical trials, but if it occurs, contact your doctor right away for treatment. Rapid weight loss, changes in hormone secretion in the gut, and reduced gallbladder emptying are all potential links between semaglutide and gallbladder disease (7).

Hair Loss

About 3% of people taking semaglutide for weight loss reported hair loss. Losing weight quickly can be a physical stressor on your body, resulting in hair shedding, a condition called telogen effluvium. This condition causes more hair follicles to enter the resting phase, leading to increased hair shedding.

Nutritional deficiencies can also cause hair loss. Check with your doctor to see if you need any nutritional supplements while taking semaglutide.

Headache

Changes in blood sugar levels, dehydration, hormonal changes, or how semaglutide acts on the hypothalamus, a part of the brain that controls appetite, are all potential triggers for headaches when taking semaglutide.

However, it is unclear whether headaches and semaglutide use are directly related. The only clinical trials that mentioned headaches were when it was taken at a higher dose as an anti-obesity medication. About 23% of participants taking semaglutide reported headaches, but so did 12% of participants taking a placebo (8).

Indigestion/Heartburn

Since semaglutide slows your stomach’s emptying, it can cause indigestion because food sits in your stomach longer. You may also notice bloating, fullness, and abdominal discomfort. These symptoms can worsen if you eat large or high-fat meals (9).

Heartburn is a symptom of indigestion and is a burning sensation in the middle of your chest. Heartburn is more likely to occur right after eating, especially when lying down or bending over.

Chew your food thoroughly and consume more frequent, smaller meals to reduce your risk of indigestion and heartburn. Stay upright for 30 minutes or more to prevent food from refluxing from your stomach into the esophagus. Avoid foods known to trigger indigestion and heartburn, such as caffeine, alcohol, fried or spicy foods, onions, garlic, chocolate, and peppermint.

Kidney Problems

In rare cases, semaglutide is associated with acute kidney injury. This may be due to rapid weight loss, dehydration, or the worsening of a pre-existing kidney condition (10).

Tell your doctor about all previously diagnosed medical conditions you may have, as well as all medications you are taking. If you have vomiting or diarrhea and are unable to stay hydrated, contact your doctor, especially if you have concentrated urine, are urinating infrequently, or notice swelling of your hands and feet.

Low Blood Sugar

Semaglutide increases insulin release from the pancreas in response to a meal. Insulin lowers your blood sugar and can cause hypoglycemia, but it is not common with semaglutide because its effects are limited to releasing insulin only after a meal (9).

Hypoglycemia is more common if you combine semaglutide with another blood-sugar-lowering medication such as insulin or sulfonylureas. Tell your doctor if you take other medications to lower your blood sugar, as you may need a dosage change when you start semaglutide.

Nausea and Vomiting

Nausea and vomiting are some of the more common semaglutide side effects. Semaglutide slows stomach emptying. This means that food sits in your stomach longer. This can help you feel full longer, but it can also trigger nausea and vomiting. In clinical trials, about 20% of people taking semaglutide reported nausea.

All the GLP-1 diabetes and anti-obesity medications cause nausea and vomiting. The symptoms are worse when you first start treatment and when your medication dose is increased (8, 11). Symptoms usually develop within the first week to months after starting semaglutide and then gradually improve (1). The dosage of semaglutide should be slowly increased to reduce the risk of nausea. If your nausea persists or worsens, contact your healthcare provider to see if a dosage increase should be delayed or if you should decrease your medication dose.

Most gastrointestinal side effects are described as mild-to-moderate in intensity. Researchers found women are more likely to have nausea and vomiting from semaglutide, but stomach-related severe side effects are equally common in men and women. Increasing age is also associated with increased nausea and vomiting when taking semaglutide. Overall, increasing age and body weight were most strongly correlated with increased nausea and vomiting with semaglutide (1).

To help minimize nausea and vomiting when taking semaglutide:

• Eat smaller meals
• Eat slowly and chew your food thoroughly
• Avoid high-fat foods
• Stay hydrated
• Avoid irritating foods, such as spicy or greasy foods
• Avoid ultra-processed foods and alcohol
• Stay upright after eating to reduce heartburn
• Sip ginger or peppermint tea

Pancreatitis

Pancreatitis, or inflammation of the pancreas, is a rare side effect when taking semaglutide. While rare, pancreatitis is serious and can even be life-threatening. Symptoms of pancreatitis include severe abdominal pain, nausea, vomiting, and/or jaundice, which is a yellowish tinge to the skin and eyes.

How semaglutide increases the risk of pancreatitis is not clear. One theory is that semaglutide stimulates increased activity in the pancreas, and this could lead to inflammation. Semaglutide and other GLP-1 agonists may increase the production of digestive enzymes in the pancreas, triggering inflammation (12).  

Rebound Weight Gain

Obesity is a chronic disease. Semaglutide is intended to be taken long-term to control appetite and support weight loss. Longer-term studies show that as long as semaglutide continues, weight loss will continue. Weight regain is common when the medication is stopped (13). In one study, two-thirds of study participants regained their lost weight after they stopped taking semaglutide (13).

If you plan to stop taking semaglutide at some point, it is important to establish healthy eating and exercise habits to help maintain your weight loss. Before stopping semaglutide, talk to your healthcare provider to discuss the risks and benefits of stopping this medication.

Thyroid Tumors

Semaglutide has a boxed warning for thyroid tumors. This is the strictest warning the FDA requires drug manufacturers to include on their labels. In animal studies, rodents developed thyroid tumors in response to GLP-1 agonists. This increased risk has not been confirmed in human studies.

Contraindications to taking semaglutide include a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) type 2. If you have a lump in your neck or any pressure when swallowing or breathing, contact your doctor.

Over the last decade, the number of effective weight-loss medications has increased. If you experience side effects when taking semaglutide, contact your doctor to learn more about other weight-loss medication options.

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