Are you new to the medical weight loss world? You might still have several questions going on in your head. Some of those concerns are regarding the side effects you might experience while taking semaglutide. 

When it comes to semaglutide, the side effects fall into two distinct categories: common and serious. The majority of them are common, manageable side effects that usually go away once your body gets used to the medication. 

However, there are some serious side effects that require urgent medical care and could be life-threatening if you just ignore them. 

Here, we are going to cover everything you need to know about all the possible side effects when you take semaglutide. From everyday digestive symptoms to rare (but serious) warning signs that require immediate action. 

In addition, we will also cover some practical strategies to help you manage the most common side effects and explain why it’s important to understand how these differences can make all the difference in your treatment journey. 

Quick Guide: Common vs Serious Semaglutide Side Effects

Common side effects include nausea, vomiting, diarrhea, constipation, abdominal pain, headaches, dyspepsia (upset stomach), and belching. Keep in mind that these GI side effects are usually more prominent during a dose escalation phase, but they tend to reduce when your body adapts to the medication. 

Serious side effects require immediate medical attention and include signs of pancreatitis (inflammation of the pancreas), gallbladder problems, severe allergic reactions, signs of severe dehydration or acute kidney injury, possible intestinal blockage, and sudden changes in your vision. 

These patterns and thresholds reflect the latest FDA-approved labeling for Weogvy and Ozempic. These warning signs can help you make informed decisions regarding the current medication you are taking. 

Are you feeling unsure about a symptom that you are experiencing? Take our no-obligation intake to message with your clinical team and get personalized guidance. 

How Semaglutide Works And Why GI Side Effects Happen

Semaglutide mimics a natural hormone called GLP-1, which enhances glucose-dependent insulin secretion, reduces appetite, and significantly slows gastric emptying. This effect on the stomach emptying is the main reason why you experience GLP-1 side effects, such as nausea, feelings of fullness, reflux, and constipation. 

So, why does it happen? 

The medication basically tells your stomach to hold onto food for a bit longer, which helps with weight loss by keeping you full for longer periods. However, this also explains why many people experience that uncomfortable “too full” feeling, especially when first starting the treatment or after eating larger portions. 

For most, GI symptoms are usually the strongest during the first weeks of treatment and typically improve when your body adapts to the medication. That is why FDA-approved protocols usually start at lower doses and gradually increase. 

Common Side Effects (Usually Manageable)

The most common side effects (happening in more than 5% of patients according to clinical trials) revolve around the digestive system. These include nausea, diarrhea, constipation, vomiting, and abdominal pain. 

These GI symptoms are usually the strongest during the first stages of the medication or during dose titration periods. Additionally, many have reported symptoms like headaches, fatigue, dizziness, dyspepsia (upset stomach), bloating, and belching. 

But there are some things that you can do to help reduce these GI symptoms:

• Eat smaller, more frequent meals rather than large meals. 
• Avoid spicy, fatty, or greasy foods since they can irritate your stomach. 
• Stay hydrated by drinking 20-30 small sips per hour throughout the day. 
• Consider ginger supplements or over-the-counter anti-nausea medication (make sure you speak with your healthcare provider first). 
• Add fiber gradually if you suffer from constipation rather than making sudden dietary changes. 

Keep in mind that if your vomiting or diarrhea doesn’t go away and interferes with your daily activities, contact your healthcare provider immediately. They may recommend an adjustment in your titration schedule or prescribe supportive medications to help you through the adjustment period. 

Serious Risks: What To Watch For And Why They Matter

While most semaglutide side effects are manageable, there are certain serious semaglutide side effects that require immediate medical attention and could be life-threatening if they are left ignored. 

Pancreatitis

Warning signs: Severe, persistent upper abdominal pain that may radiate to the back, and it’s often accompanied by nausea and vomiting. This pain typically feels different from a regular stomach ache since it’s intense and doesn’t seem to improve with position changes or antacids. 

Action required: Stop taking semaglutide immediately and seek urgent medical care. Pancreatitis is a life-threatening condition and should be handled as soon as possible. 

Why it matters: GLP-1 receptor agonists carry a class-wide association with pancreatitis risk, which is why you often see it in the FDA labelling across every form of semaglutide available on the market. 

Gallbladder/Biliary Disease

Recent meta-analysis of 76 randomized controlled trials shows there is an increased risk of gallstones (cholelithiasis) and gallbladder inflammation (cholecystitis) when using semaglutide treatment. This risk often seems stronger when there are higher doses, longer treatment duration, and when used for weight loss. 

Warning signs: Upper-right abdominal pain, fever, and yellowing of the skin or eyes. 

Action required: Seek immediate medical evaluation if you experience any of these symptoms. 

Thyroid C-Cell Tumors (MTC) Warning

Semaglutide carries a boxed warning due to thyroid C-cell tumors seen in rodent studies. While it’s still not known if this is something that can affect humans, right now the FDA has issued a warning for those with a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 

Warning signs: New neck masses, persistent hoarseness, or difficulty swallowing. 

Action required: Report any new symptoms to your healthcare provider right away. 

Diabetic Retinopathy Considerations

The SUSTAIN-6 trial identified higher diabetes retinopathy complications for people with pre-existing retinopathy who experienced a rapid A1c reduction. However, a recent 2025 meta-analysis found no overall increase in diabetic retinopathy risk but identified a potential sign for non-arteritic anterior ischemic optic neuropathy (NAION). 

Action required: Report any sudden changes in your vision or vision loss to get an immediate evaluation. 

Acute Kidney Injury (AKI) & Dehydration

Severe gastrointestinal fluid losses from persistent vomiting or diarrhea can lead to dehydration and acute kidney injury. 

Warning signs: Very low urine output, swelling in legs or feet, sudden weight gain, or feeling extremely weak and dizzy. 

Action required: Seek immediate medical attention to get the right evaluation and potential IV fluid therapy. 

Intestinal Blockage & Severe Gastroparesis

FDA labeling and safety communications include ileus (intestinal blockage) and severe gastroparesis (stomach paralysis). 

Warning signs: Severe and persistent abdominal distention, severe abdominal pain, and persistent vomiting. 

Action required: If you experience any of these symptoms, make sure you seek immediate medical care. 

Hypoglycemia With Insulin or Sulfonylurea

While semaglutide alone can rarely cause dangerously low blood sugar levels, the risk increases when you combine it with insulin or a sulfonylurea medication. 

Action required: Talk to your healthcare provider to consider reducing the dose of these medications when starting semaglutide. Make sure you also monitor your blood sugar levels closely and know the signs (and what to do) for hypoglycemia (low blood sugar). 

Hypersensitivity/Anaphylaxis (Rare)

Though it’s uncommon, there is always the risk of having a severe allergic reaction, including anaphylaxis. 

Warning signs: Facial swelling, difficulty breathing, widespread rash, and severe itching. 

Action required: Stop semaglutide immediately and seek urgent medical care. 

Do you need individualized risk counseling based on your health history? Book your intake to message with one of our clinicians about your specific situation. 

Long-Term Effects: Benefits, Tradeoffs, And What Happens If You Stop

Knowing what semaglutide’s long-term effects are can help you make informed decisions about continuing the treatment. Here, we are going to go over what those long-term effects. 

Remember that you should always follow your healthcare provider’s recommendations to stop (or continue) the treatment. 

Cardiovascular Benefits

The SELECT trial demonstrated significant heart health benefits for adults with overweight or obesity and established cardiovascular disease (but without diabetes). The study showed that those taking 2.4 mg of semaglutide had a 20% reduction in major adverse cardiovascular events (MACE_ compared to the placebo group over three years. 

Weight Maintenance vs. Discontinuation 

In the STEP-1 extension study, participants regained approximately two-thirds of their weight loss when they stopped taking semaglutide. That is why some people recommend ongoing treatment and/or making lifestyle changes to promote weight maintenance. 

Observational electronic health record data also shows that some patients do manage to keep their weight off after stopping the treatment. However, individual results vary based on lifestyle factors, underlying metabolism, and other health conditions. 

Long-Term Eye Health Considerations 

Patients with pre-existing diabetic retinopathy who experience rapid glucose improvements may see an increase in their retinopathy symptoms. Do keep in mind that there is currently no data that shows there is an increase in diabetic retinopathy. However, there are some emerging notes regarding the potential NAION (non-arteritic anterior ischemic optic neuropathy) signals. 

Who Should Not Take Semaglutide (And Who Needs Extra Caution)

There are some people who should avoid taking semaglutide entirely, while others might require careful monitoring and potentially have a modified treatment approach. 

Do not use semaglutide if you have: 

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Serious hypersensitivity to semaglutide or any components in the formulation. 

Currently, it’s not recommended to take semaglutide if you are pregnant. Women who are of childbearing age (and are thinking about getting pregnant) should discuss everything with their healthcare provider before starting treatment. 

Several health conditions require tailored monitoring and a modified treatment approach: 

• History of pancreatitis: It requires careful risk-benefit assessment and close monitoring. 
• Active gallbladder disease: You may need treatment of any underlying conditions before you start the treatment. 
• Advanced diabetic retinopathy: It requires ophthalmology coordination and close monitoring. 
• Chronic kidney disease with recent acute kidney injury: You may need careful monitoring of kidney function. 
• Currently using insulin or sulfonylurea: It may require medication adjustments to prevent low blood sugar levels. 

These situations don’t mean you automatically cannot get semaglutide treatment, but they do require individualized assessment and enhanced monitoring protocols. 

Managing Side Effects Like A Pro (Dose, Diet, and Timing)

Semaglutide can have several side effects, but there are some strategies that can help you manage them, such as dosing, dietary choices, and timing. 

Follow Label Titration Protocols

The FDA-approved titration schedule exists for a good reason, and it’s to start low, go slow, and escalate every four weeks as tolerated. Normally, semaglutide side effects are strongest during the first weeks of treatment or when there are increased doses. 

It can be tempting to increase doses faster than recommended, even if you are tolerating the current dose well. Your body needs time to adapt to each level before moving on to the next higher dosage. 

Strategic Meal Planning 

• Portion control: Eat smaller, more frequent meals rather than large meals per day. Remember that your stomach empties more slowly when taking semaglutide, so it’s best to have smaller portions to prevent that uncomfortable “stuffed” feeling. 
• Food timing: Consider eating your largest meal earlier in the day when your stomach motility tends to be better. Many find that eating too heavily in the evening can lead to overnight discomfort. 
• Food choices during titration: Temporarily limit high-fat, greasy, or very spicy foods while your body adjusts. These foods can worsen nausea and create an upset stomach while you get used to the medication. 

Hydration Strategy 

Sip fluids steadily throughout the day rather than drinking large amounts at once. Aim to get 20-30 sips of water in an hour to stay hydrated without overwhelming your slower-emptying stomach. 

Managing Specific Symptoms 

For constipation: Add fiber gradually to your diet and consider getting an over-the-counter stool softener (just make sure you speak with your healthcare provider first). Keep in mind that sudden increases in fiber can worsen bloating and gas, and may even lead to more constipation. 

For nausea, taking ginger supplements, eating smaller, more frequent meals, and avoiding strong food odors can help manage your nausea symptoms. If it continues, you might benefit from an over-the-counter anti-nausea medication, but it’s always best to talk with your healthcare provider first. 

Oral vs Injectable: Do Side Effects Differ?

Rybelsus (oral semaglutide) and injectable formulations share the same active ingredient, but since they have different delivery methods and doses, they have specific side effects. 

Rybelsus uses a specialized absorption enhancer to help semaglutide withstand the digestion process. This requires specific administration rules: take it on an empty stomach with no more than 4 ounces of water, then wait at least 30 minutes before eating, drinking, or taking any other medication. 

Regarding the GI side effects of both oral and injectable semaglutide, they are pretty much the same since they come from semaglutide’s mechanism rather than the delivery method. However, there might be a difference in the timing or intensity due to its absorption pattern. 

Rybelsus requires strict adherence to administration rules to make sure it has proper absorption. Taking multiple tablets together or not following the timing requirements can significantly reduce the effectiveness of the medication.

Surgery Or Procedures While On Semaglutide

Updated multi-society guidance from anesthesiology organizations provides clearer directions for those undergoing surgery while they are taking GLP-1 medications (like semaglutide). 

Most patients can continue taking their regular semaglutide dosing before getting elective surgery. The previous practice of having to stop all GLP-1 medications has been abandoned due to newer evidence and expert consensus. 

However, those who have a higher risk of GI complications may benefit from getting a 24-hour clear liquid diet before getting a procedure. However, as always, it’s best to consult with a healthcare provider to determine the best course of action for you. 

About Compounded Semaglutide Safety

The FDA has issued an important warning about unapproved and illegally marketed semaglutide products that it’s important for you to understand. 

Compounded semaglutide products may contain inconsistent dosing, unknown ingredients, or salt forms that haven’t undergone the same safety testing as FDA-approved medications. As a result, these variations can potentially increase the risk of semaglutide side effects or reduce its effectiveness. 

If you are considering compounded semaglutide, make sure you are working with: 

• State-licensed compounding pharmacies
• Licensed healthcare providers who can properly supervise your treatment
• Facilities that follow appropriate quality standards and testing protocols 

Keep in mind that improperly compounded medications might have a higher risk of contamination, incorrect dosing, or unexpected reactions. That is why the side effects of these medications may be different from the ones we’ve previously mentioned. 

FAQs

How long do common side effects last?

Most GI side effects usually improve as you complete the titration process and your body adapts to each dose level. If the symptoms persist or worsen, make sure you consult with your healthcare provider to potentially slow the titration schedule or add any supportive medication (like anti-nausea medication). 

What are the early signs of pancreatitis on semaglutide?

Watch for severe, constant upper-abdominal pain that radiates to your back and that is usually accompanied by nausea and vomiting. Keep in mind that this pain is not like a regular stomach ache; it’s usually intense, persistent, and doesn’t improve if you change positions. 

If you experience any of the previous symptoms, stop taking semaglutide and seek urgent medical care. 

Does semaglutide cause thyroid cancer?

Rodent studies have shown that taking semaglutide can increase the risk of C-cell tumors. That is why there are currently boxed warnings in every semaglutide medication. However, we still don’t know the effects on humans. 

As a precaution, it’s best to avoid taking semaglutide if you have a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). And, if you see any new neck masses, persistent hoarseness, or difficulty swallowing, talk with your healthcare provider. 

Can it harm the gallbladder?

Some clinical trials and meta-analyses show there is an increased risk of gallstones and gallbladder inflammation, especially with higher doses, longer treatment duration, and weight-loss applications. If you experience upper-right abdominal pain, fever, or jaundice (yellow coloring of skin or eyes), seek medical attention. 

What about my eyes?

Patients who have pre-existing diabetic retinopathy and who experience rapid blood sugar improvements need closer monitoring. While studies haven’t shown an increased risk, there is a concern for non-arteritic anterior ischemic optic neuropathy (NAION). If you experience any sudden changes in your vision, speak with your healthcare provider. 

Are long-term effects positive or negative?

Overall, there are some positive effects when using semaglutide. There is sustained weight loss as well as cardiovascular protection. However, it’s important to weigh these benefits against the possible side effects you might experience when taking the medication. 

Do I need to stop before surgery?

Usually no, according to an updated 2024-2025 multi-society guidance from anesthesiology organizations. Patients who have a higher risk of GI problems are best to follow a clear liquid diet for 24 hours before surgery. It’s best to speak with your doctor to learn if it’s best to continue or if you should stop the medication before any surgery. 

Ready to get personalized semaglutide guidance based on your specific health situation? Start your OnlineSemaglutide.org intake today to connect with an experienced clinician who can help you navigate your treatment journey safely and effectively.