The side effects of semaglutide — what to expect

Semaglutide is the active ingredient in 3 brand-name medications — Wegovy, Ozempic, and Rybelsus. It’s also available as compounded semaglutide from compounding pharmacies. Llike any medication, all of these drugs can have side effects — some minor, some more serious. In this post, we cover the side effects of semaglutide and what you might expect when you take it along with other things you need to know.

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What is semaglutide?

Semaglutide belongs to a class of drugs known as glucagon-like peptide-1 receptor agonists. These drugs mimic a natural hormone called glucagon-like peptide-1 (GLP-1) that’s produced naturally in your small intestine. GLP-1 and GLP-1 agonist medications:

• Increase insulin production, reduce appetite, and slow down digestion so you feel full longer, eat less, and lose weight.
• Help regulate blood sugar levels and lower A1C levels to help people with type 2 diabetes better manage their condition. 
• Help reduce the risk of major cardiovascular events, such as stroke, heart attack, or death for people with known heart disease who meet the criteria for taking semaglutide.

Semaglutide is the active ingredient in an oral pill called Rybelsus, weekly injections sold as brand names Wegovy and Ozempic, and as compounded versions of the injection or oral tablet.

Ozempic 

Ozempic (semaglutide) was approved by the U.S. Food and Drug Administration (FDA) to lower blood sugar (glucose) levels and A1C in people with type 2 diabetes when used with a reduced-calorie diet and increased activity in 2017. It’s also since been FDA-approved to help reduce the risk of major cardiovascular events, like stroke, heart attack, or death for people with type 2 diabetes and existing heart disease. It’s intended to be used with a reduced-calorie diet and increased exercise.

Ozempic isn’t approved for weight loss and is used at a lower dose than Wegovy. People who take it often lose weight though. In clinical trials, people with type 2 diabetes who took 2 milligrams of Ozempic per week lost at least 5% of their body weight in 40 weeks. Some people lost more than 10% of their body weight.

Because people lost weight on Ozempic, Novo Nordisk, who makes it, got a version of it approved just for weight loss under the brand name Wegovy.

Wegovy

Wegovy was FDA-approved in 2021 for weight loss and chronic weight management when used with a reduced-calorie diet and increased activity. It’s approved for people with obesity (a body mass index [BMI] of 30 or more) or overweight (a BMI of 27 or more) with at least 1 weight-related health condition such as high cholesterol, high blood pressure, or type 2 diabetes. It’s also approved to reduce the risk of major cardiovascular events, like death, heart attack, or stroke, in adults with known heart disease and obesity or overweight.

In clinical trials for Wegovy, people who changed their diet and exercise patterns lost an average of 14.9% of their body weight in 68 weeks.

Read Wegovy reviews to see what patients say about Wegovy’s side effects. Also, learn more about Ozempic vs Wegovy.

Rybelsus

Rybelsus (semaglutide) is an oral GLP-1 medicatoin and an alternative to Ozempic. It was FDA-approved in 2019 to improve control of blood sugar in adult patients with type 2 diabetes, along with diet and exercise. Like Ozempic, people taking it may lose weight. In a phase 3 clinical trial, people taking 50 milligrams of oral semaglutide lost an average of 15.1% of their body weight in 68 weeks. 

Compounded semaglutide

Compounded semaglutide is also available. A compounding pharmacy can create a compounded medication in small batches or a custom version from scratch based on your specific needs. A provider may prescribe a compounded version of a medication so the patient can save money, when they have trouble finding Rybelsus, Ozempic, or Wegovy in stock, or due to allergies.

Common side effects of semaglutide for weight loss

Based on clinical trials conducted with people taking Wegovy for weight loss, the most common side effects of semaglutide are gastrointestinal symptoms. 

The semaglutide side effects users reported most often in clinical trials were:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Abdominal pain
• Headache
• Fatigue

More than 20% of trial participants reported these side effects, with 44% reporting nausea and 30% reporting diarrhea compared to 24% or fewer for vomiting, constipation, and abdominal pain. 

Less common, but milder, side effects of semaglutide injections

Some side effects of semaglutide injections for weight loss seen in clinical trials are less common but still mild and include:

• Indigestion (dyspepsia)
• Dizziness
• Abdominal distention (bloating)
• Belching (eructation)
• Low blood sugar (hypoglycemia) in people with type 2 diabetes
• Flatulence
• Gastroenteritis
• Gastroesophageal reflux disease (GERD)
• Gastritis
• Gastroenteritis viral
• Hair loss
• An abnormal touch sensation (dysesthesia)

These side effects were reported fewer than 9% of trial participants. 

Side effects for other forms of semaglutide, including Ozempic, Rybelsus, and compounded semaglutide are similar but not identical to the side effects for Wegovy, which is the primary form of semaglutide for weight loss. Learn more about compounded semaglutide below. Also learn about Ozempic side effects. Note that Rybelsus and Ozemic share side effects except that Ozempic can cause injection site reaction while Rybelsus doesn’t.

Even though common semaglutide side effects tend to be mild, tell your healthcare provider if you experience them. They can help you manage them and adjust your Wegovy dose or other semaglutide dose or increase your dose more slowly.

Precautions and serious side effects of semaglutide

Serious side effects of semaglutide for weight loss are possible, most are fairly rare. They include:

• Acute pancreatitis (inflammation of the pancreas) — 4 people in clinical trials who took Wegovy and 1 person on a placebo got acute pancreatitis. Symptoms of acute pancreatitis include persistent, severe abdominal pain that sometimes radiates to the back and is accompanied by vomiting. 
• Acute gallbladder disease, including gallstones (cholelithiasis). In clinical trials, 1.6% of people on Wegovy had gallstones compared to 0.7% on the placebo. Gallstones may cause no symptoms. When they do trigger symptoms, they can include steady, severe upper abdominal pain, pain between your shoulder blades or in your right shoulder, nausea, vomiting, fever, chills, or jaundice (yellow skin or eyes). Gallbladder disease is especially common in people who lose large amounts of weight quickly, whether with semaglutide or another way.

• Hypoglycemia (low blood sugar) in people with type 2 diabetes. In clinical trials for semaglutide as Wegovy, 6.2% of people taking Wegovy compared to 2.5% on a placebo had significant hypoglycemia. The risk for hypoglycemia is higher for people on other medications to manage blood sugar like insulin or sulfonylureas. Hypoglycemia in patients without type 2 diabetes wasn’t assessed in clinical trials.  
• Acute kidney injury. In clinical trials, 7 people taking Wegovy had acute kidney injury compared to 4 on placebo. Kidney damage can occur both in people with pre-existing kidney conditions and those with no history. Most of these adverse events were reported by people who experienced nausea, vomiting, and/or diarrhea that caused dehydration. If you take Wegovy, make sure you stay hydrated to help reduce the risk of kidney injury.
• Retinal disorders in people with type 2 diabetes. 6.9% of people on Wegovy in clinical trials who had type 2 diabetes experienced retinal disorders compared to 4.2% on placebo — primarily diabetic retinopathy and non-proliferative retinopathy. Rapid improvement in glucose control has been associated with temporarily worsened diabetic retinopathy. There’s not yet long-term data on how using semaglutide for blood sugar control affects diabetic retinopathy.
• Increased resting heart rate. In trials, more adults taking Wegovy than placebo had an increase in resting heart rate from 1 to 4 beats per minute on average.
• Hypotension (low blood pressure) and syncope (loss of consciousness due to low blood pressure). 1.3% of people taking Wegovy in trials had hypotension compared to .4% on placebo. And .8% on Wegovy had an episode of syncope versus .2% on placebo. Some episodes were tied to gastrointestinal problems or the simultaneous use of blood pressure medications. 
• Appendicitis. A small number of trial participants got appendicitis during clinical trials.  And more people on Wegovy had it than those on placebo — .5% on Wegovy compared to .2% on placebo.  
• Gastrointestinal adverse reactions as previously mentioned occurred in clinical trials and were more common in people taking semaglutide than the placebo. 4.3% of adults taking semaglutide vs 0.7% on placebo quit the trial because of gastrointestinal issues. 
• Injection site reactions. 1.4% of people on Wegovy compared to 1.0% on placebo during clinical trials had pruritus (itching), erythema (redness), inflammation, induration (thickening), and/or irritation at the injection site.
• Hypersensitivity or serious allergic reactions like anaphylaxis (a severe, possibly life-threatening allergic reaction), angioedema (swelling deep in the skin) were reported in clinical trials. When taking semaglutide, monitor yourself for any sign of hypersensitivity and stop taking it if you develop a rash, itching, or swelling.
• Fractures. In trials to assess semaglutide’s effectiveness for reducing the risk of major cardiovascular events in adults, hip and pelvic fractures were reported and occurred more often in women under 75 and patients 75 or older.
• Urolithiasis (kidney stones). In trials to assess semaglutide’s effectiveness for reducing the risk of major cardiovascular events in adults, more people taking Wegovy developed kidney stones than those on placebo — 1.2% vs 0.8% respectively.  If you take Wegovy, make sure you stay hydrated to help reduce the possibility of kidney stones.
• Dysgeusia (a taste disorder). In trials, 1.7% of people on Wegovy developed dysgeusia compared to .5% of people on the placebo.
• Elevated amylase and lipase levels. Amylase and lipase are digestive enzymes that help your body break down carbohydrates and fats. In trials, adults and children taking Wegovy had elevated levels of both enzymes. It’s not known whether the elevations reported pose any health risk. 
• Elevated liver enzymes. In trials to assess semaglutide’s effectiveness for reducing the risk of major cardiovascular events in adults, increases in total bilirubin greater than or equal to 3 times the upper limit of normal were seen in .3% of people taking Wegovy versus .2% of people taking the placebo. High levels of bilirubin can cause serious health risks. Monitoring liver function is important when taking Wegovy or compounded semaglutide.

Clinical trials are done before a medication is approved by the FDA. In some cases, as with semaglutide in Wegovy, after a medication is approved and sold, other adverse events, called “postmarketing experience” are reported. In the case of Wegovy, additional adverse events reported after it was released to market include: 

• Gastrointestinal disorders, including acute pancreatitis, necrotizing pancreatitis (when part of the pancreas dies) that sometimes results in death, and ileus when muscles in the intestine stop working and food and waste can’t pass through the body normally. 
• Hypersensitivity reactions that include anaphylaxis, angioedema, rash, and urticaria (itchy welts on the skin)
• Acute kidney injury

How common these post-marketing side effects of semaglutide are or if they are directly linked to Wegovy or the result of another medication isn’t known.

Side effects of compounded semaglutide vs Wegovy 

Compounded medications don’t go through clinical trials or other testing. The pharmacies that make them are regulated by the FDA, but compounded medications themselves are not. And while, when from reputable compounding pharmacies, they use pharmaceutical-grade ingredients, they may also use other ingredients not found in Wegovy, Ozempic, and Rybelsus.

So, while the basic side effects of compounded semaglutide may be similar to Wegovy and include nausea, vomiting, and gastrointestinal issues, they may have other side effects as well.  For example, it’s possible to have an allergic reaction to an inert ingredient used in compounded semaglutide that’s not used in a brand-name semaglutide.

Drugs that may interact with semaglutide

Like any other prescription, semaglutide in any form can interact with other medications. Drugs known to interact with Wegovy, and that may also interact with Ozempic, Rybelsus, or compounded semaglutide, include:

• Insulin or other diabetes medications like sulfonylureas (insulin secretagogues) may increase the risk for hypoglycemia (low blood sugar). If you’re on insulin or an insulin secretagogue, work with your healthcare provider. They may reduce the dose of insulin or the secretagogue to reduce your risk of hypoglycemia. 
• Some oral medications. Because semaglutide slows down how quickly food leaves your stomach (gastric emptying), it can affect how some oral drugs are absorbed by your body. If you take other medications, work with your healthcare provider to ensure they continue working as expected.

Warnings for semaglutide

In addition to the potential for serious side effects, there are warnings for semaglutide to be aware of.

• Thyroid C-cell tumor risk. Semaglutide carries an FDA boxed warning for thyroid C-cell tumors. A boxed warning is the most serious warning the FDA issues. The warning is based on animal studies. It’s unknown if semaglutide increases the risk of thyroid C-cell tumors, including medullary thyroid cancer, for people. But, people with a personal or family history of thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN 2) should tell their provider, watch for symptoms of thyroid problems,and be monitored.
• Suicidal ideation and behavior. Suicidal ideation and behavior were reported in clinical trials of semaglutide for weight management. While you’re on semaglutide, watch for signs of worsening depression, suicidal thoughts or behavior, and/or any changes in behavior or mood. Stop taking it and contact your provider if you have any suicidal thoughts or behaviors. People with a history of suicidal attempts or active suicidal ideation shouldn’t take semaglutide for weight loss.

And always discuss your medical history with your healthcare provider before starting semaglutide. 

When not to take semaglutide

Semaglutide for weight loss is safe and effective for most people. In clinical trials, similar percentages of people taking semaglutide reported adverse events compared to people taking placebo (89.7% and 86.4%, respectively).

But every medication has contraindications, which are medical symptoms or conditions that make taking that specific drug less safe or potentially harmful. 

The main contraindications for semaglutide are:

• Having a personal or family history of medullary thyroid cancer (MTC). Semaglutide may increase the risk of thyroid C-cell tumors. People with a history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN 2) shouldn’t take semaglutide.
• Known hypersensitivity. If you’ve had a serious allergic reaction to semaglutide or any of its ingredients in the past, you could have anaphylaxis or angioedema if you take semaglutide. 

Other people who should be cautious when considering semaglutide include:

• People who are pregnant or thinking about getting pregnant. Semaglutide is contraindicated during pregnancy because it may harm the fetus. If you might get pregnant, use effective contraception while taking semaglutide. And stop taking or don’t start semaglutide if you’re pregnant or plan to get pregnant.
• Women who are breastfeeding. There’s no data on whether or not semaglutide or its metabolized components show up in human breastmilk, how it affects breastfed babies, or a breastmilk production. But semaglutide has been found in the milk of lactating rats. When medication is found in animal milk, it will likely be present in human milk too. If you’re considering taking semaglutide while breastfeeding, work with your provider to balance the benefits and potential problems for you and your infant to decide whether to start or continue taking it or not.
• People with severe gastrointestinal disorders. People with issues, like gastroparesis (delayed stomach emptying), should avoid semaglutide. Because it slows gastric emptying, it may worsen gastrointestinal conditions.

For many people, deciding whether a medication is the right choice is a process of balancing benefits and potential risks. Ask your healthcare provider to be sure a semaglutide prescription is right for you.

How to avoid side effects from semaglutide

Most people taking semaglutide for weight loss find that, if they experience side effects, they’re mild-to-moderate and are most common when first starting semaglutide or increasing their dose. But whether you have side effects from semaglutide or not, there are ways to avoid or minimize them including the following.

• Understand and follow your provider’s instructions on dose and timing. Your provider will have you start with a smaller dose and increase your Wegovy dose gradually. This helps your body adjust and reduces side effects like nausea and vomiting. Always follow your provider’s dosing instructions, in part to minimize or avoid side effects.
• Eat smaller, more frequent meals to help manage nausea and indigestion.
• Avoid fried, fatty, and spicy foods that can make nausea and stomach discomfort worse.
• Stay hydrated and consider avoiding caffeine and alcohol. Drink plenty of water, especially if you experience vomiting or diarrhea.
• Follow more general best practices for your health. Get enough sleep, and exercise regularly.
• Tell your provider about any medications or supplements you take.

How to manage the side effects of semaglutide

If you can’t avoid side effects while on semaglutide, there are things you can do to manage them.

• Nausea. If you’re eating smaller, more frequent meals and avoiding spicy and fatty foods and still have nausea, try eating bland foods like crackers and toast, and avoid strong smells. Taking ginger or peppermint may also help.
• Diarrhea. If you’re staying hydrated and still have diarrhea, try more liquids and drink electrolyte-rich drinks like coconut water or Gatorade.
• Stomach pain. If you have stomach discomfort, talk to your healthcare provider about trying antacids or other over-the-counter or prescription remedies.
• Constipation. If you’re watching your diet and getting regular exercise but you still have constipation, talk to your healthcare provider about over-the-counter remedies that may help.
• Low blood sugar. If you take other diabetes medications, monitor your blood sugar closely. If you’re eating smaller, more frequent meals and you still experiencing low blood sugar, speak to your provider about how to remedy the problem. Have a snack or glucose tablets on hand in case you feel symptoms of hypoglycemia.

Over-the-counter medications can target specific side effects, such as nausea, vomiting, or constipation. Talk to your provider before taking any medication alongside semaglutide though. 

And if you experience side effects of semaglutide for weight loss that are persistent or get worse, there are alternative weight loss medications, including alternatives to Wegovy. Ask your healthcare provider about adjusting your dose or alternative treatments.

What to do if you miss a dose of semaglutide

Missing a dose can affect side effects and how effective your medication is overall. If you miss a dose of semaglutide, here’s what to do:

• If it’s within 5 days of your missed dose, take the dose as soon as you remember.
• If more than 5 days have passed, skip the missed dose and take your next scheduled dose at the regular time.
• Don’t double up on doses to make up for a missed one. This can increase your risk for side effects like nausea, vomiting, and hypoglycemia.

If you miss and then take a dose, you might have more side effects like nausea. That’s because your body may need to readjust to taking semaglutide. But getting back in the rhythm of regular doses should help stabilize side effects.

Always ask your healthcare provider if you’re unsure how to handle a missed dose.

Key takeaways

• The most common side effects of prescription semaglutide for weight loss are gastrointestinal issues. People report nausea, vomiting, constipation, abdominal pain, and diarrhea.
• More serious side effects of semaglutide are rare. These include, but aren’t limited to,  kidney issues and gallbladder disease.
• Some people shouldn’t take semaglutide, like those with a history of thyroid cancer or people who are pregnant or breastfeeding.
• You can reduce your risk for semaglutide side effects and manage them if you have them. Take it only as prescribed, increase your dose slowly, and avoid spicy, fatty foods.
• Talk to your healthcare provider if the side effects of semaglutide bother you. Mention all of your other medications, including over-the-counter drugs and supplements. All of these can affect semaglutide side effects.

Possible weight loss with semaglutide is a click away

Semaglutide isn’t a miracle drug, and like any medication, it has side effects. But prescription versions of semaglutide have effectively helped many people with obesity or overweight achieve their weight loss goals.

If you’re struggling with weight management or weight loss, find a qualified healthcare provider who specializes in weight loss on Klarity Health today.