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Semaglutide — the active ingredient in the brand-name meds Ozempic®, Wegovy®, and Rybelsus® — treats type 2 diabetes and obesity or overweight. If you’ve recently been prescribed this medication or are curious about getting a prescription, you probably have some questions about semaglutide side effects.
While semaglutide can be a life-changing tool and is generally considered safe and effective when taken as prescribed, side effects like nausea and upset stomach are common in the beginning. Though they typically subside after a few weeks to months.
We’ll talk about how semaglutide works and go over the common side effects you might encounter — as well as some rare but more serious risks to be aware of. Knowledge is power, and we’re here to help you feel informed and confident in your treatment journey.
Let’s dive in.
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Semaglutide is in a class called glucagon-like peptide-1 (GLP-1) receptor agonists. It works by mimicking GLP-1, a hormone the intestines naturally make.
GLP-1 plays a key role in stimulating insulin production and regulating blood sugar levels (glucose). It also suppresses appetite and boosts feelings of fullness, which can then lead to reduced food intake and potential weight loss.
Ozempic, Wegovy, and compounded semaglutide are once-weekly injections. Rybelsus, on the other hand, is taken orally once a day.
Semaglutide is used to treat both type 2 diabetes and obesity. Wegovy is FDA-approved for weight management in people with a BMI (body mass index) of 30 or higher or 27 or higher if they have at least one weight-related medical condition, such as:
High blood pressure (hypertension)
Type 2 diabetes
High cholesterol
Sleep apnea
Ozempic is FDA-approved for type 2 diabetes, but since it also contains semaglutide, it’s often prescribed off-label to help support weight management. Off-label is when a provider prescribes a medication for something other than what it was FDA-approved to treat.
Both Wegovy and Ozempic are prescribed alongside lifestyle changes like a healthy diet and increased physical activity.
Compounded semaglutide, which is available through the Hers platform, contains the same active ingredient as Wegovy and Ozempic.
Healthcare providers usually start patients on a low dose of semaglutide and gradually increase it every four weeks until they reach a long-term maintenance dose. This can help mitigate some semaglutide side effects.
The recommended maintenance dose of Wegovy is 2.4 milligrams (mg) weekly. But not everyone will need such a high dose to achieve their weight loss goals. That’s why Hers offers personalized dosing options, so you can do what works best for your body.
It’s not uncommon to experience some adverse effects with semaglutide, especially during the first few weeks of treatment or when adjusting to a higher dose.
The most common side effects of Ozempic, Wegovy, and Rybelsus are gastrointestinal, including things like:
Nausea
Vomiting
Diarrhea
Constipation
Stomach pain
It’s important to be aware of these initial reactions as your body adapts to the medication. When in doubt, keep your provider in the loop. They may be able to help you find ways to manage the side effects if they don’t go away on their own.
Semaglutide injection side effects — like skin irritation — can also occur at the injection site.
Side effects from semaglutide are expected (if they occur) at the beginning of treatment and when you increase your dose. Thankfully, many people find that these side effects subside after a few weeks as their bodies get used to it.
Some folks taking semaglutide manage nausea, diarrhea, and stomach pain by using over-the-counter medications during the adjustment period.
It’s always a good idea to keep in close communication with your healthcare provider about any side effects you experience. If your side effects are particularly severe, they may suggest slowing down your dose escalation to help your body adapt more comfortably. If significant nausea is one of your side effects, it is often possible your medical provider will prescribe a nausea medicine for you.
Remember, your healthcare provider can offer personalized advice tailored to your situation, so don’t hesitate to reach out.
Now, you may be wondering about the rare long-term side effects of semaglutide.
This medication is generally considered safe, and the benefits of taking semaglutide outweigh the risks for most people. But there’s still a possibility of more serious side effects.
According to research cited in the FDA’s prescribing information for Ozempic, some severe side effects and long-term risks include:
Pancreatitis
Acute kidney injury
Gallbladder problems
Diabetic retinopathy complications
Increased heart rate
Thyroid cancer
Mental health issues
Here’s what’s known so far about these effects.
Pancreatitis (inflammation of the pancreas) was reported during clinical trials of Ozempic. However, the findings weren’t conclusive. Translation: If pancreatitis is a potential risk, it appears to be very rare.
In a two-year clinical trial of Ozempic, acute pancreatitis — a sudden but treatable condition — was observed in a small number of patients taking Ozempic, but more cases of pancreatitis were observed in patients given a placebo.
In other words, more cases of pancreatitis were reported among those on the placebo than those using semaglutide, making it difficult to determine whether the medication was a contributing factor.
No cases of pancreatitis were reported in another two-year trial sponsored by Novo Nordisk. This trial involved participants who had obesity or overweight along with at least one weight-related health issue (excluding type 2 diabetes), who were given a 2.4 mg dose of semaglutide.
We should note that semaglutide hasn’t been studied in people with a history of pancreatitis. But if you’ve had this condition, your healthcare provider may suggest an alternative treatment.
Some studies sponsored by Novo Nordisk suggest that semaglutide may actually help reduce the risk of kidney disease over the long term. But there have also been reports of individuals taking GLP-1 medications, like semaglutide, who developed kidney issues, including worsening chronic kidney failure, especially if experiencing significant nausea or vomiting.
Acute kidney injury is when the kidneys suddenly stop functioning properly. There have been instances of kidney problems showing up in people experiencing significant nausea, vomiting, or diarrhea — conditions that can lead to dehydration and negatively impact kidney function.
If you have a history of kidney problems, let your healthcare provider know before starting semaglutide. And if you experience severe gastrointestinal side effects, your provider may want to monitor your kidney function closely to ensure everything stays on track.
Your gallbladder is in your abdomen. It stores and releases bile, which is needed to break down fats in the food you eat. One of the rarer side effects of semaglutide is related to gallbladder health, specifically gallstones — hardened pieces of bile that develop over time.
According to research, losing a significant amount of weight quickly can increase the risk of gallbladder issues, including gallstones.
In clinical trials supported by Novo Nordisk, gallstones were reported in 1.5 percent of participants taking a 0.5 mg dose of semaglutide and 0.4 percent of those taking the 1 mg dose. No cases of gallstones were reported among those who received a placebo.
Also, semaglutide may raise the risk of gallbladder disease. In further clinical trials from Novo Nordisk, 83 people taking semaglutide experienced gallbladder-related events (mainly gallstones), compared to just 39 patients on a placebo.
While many people with gallstones may not experience symptoms, it’s important to know that if a gallstone blocks your bile ducts, you might feel pain in your upper-right abdomen. If anything feels unusual, reach out to your healthcare provider.
Diabetic retinopathy is a serious eye condition that can affect folks with diabetes. It happens when blood vessels in the eyes are damaged, potentially leading to vision loss.
Semaglutide may increase the risk of complications related to diabetic retinopathy. In a two-year trial funded by Novo Nordisk, participants with type 2 diabetes and a high cardiovascular risk reported more events of diabetic retinopathy complications while taking semaglutide compared to those on a placebo.
Your risk is also higher if you have a history of diabetic retinopathy. And rapid improvements in glucose control — something that can occur with semaglutide — might temporarily worsen diabetic retinopathy. However, the long-term effects of semaglutide on this condition haven’t been thoroughly studied, so we don’t know if sustained glucose control will improve the situation over time.
There’s hope for more clarity soon, though. A study investigating the long-term effects of semaglutide on diabetic retinopathy is currently in progress and expected to conclude in 2027.
If you have a history of diabetic retinopathy, inform your healthcare provider before starting Ozempic. And if you’re already taking it, seek medical advice right away if you notice any changes in your vision.
Taking semaglutide may lead to a slight increase in heart rate — typically by two to three beats per minute, based on trials sponsored by Novo Nordisk using 0.5 and 1 mg doses of semaglutide.
The reassuring news is that this small increase hasn’t been linked to any adverse cardiac events. In fact, the benefits of GLP-1 medications like semaglutide on heart health often outweigh the risks of a modest rise in heart rate.
Long-term use of semaglutide may even lower the risk of major cardiovascular events like heart attacks, particularly in patients with type 2 diabetes.
The Wegovy drug label indicates that suicidal ideation and behaviors have been reported in clinical trials of other weight loss treatments.
There may also be concerns about other long-term mental health issues, but more research is needed to fully understand these effects.
In clinical trials sponsored by Novo Nordisk, semaglutide was compared to liraglutide — another medication used for diabetes and weight loss. Six percent of people taking semaglutide experienced psychiatric disorders over one to four years, compared to 15 percent of those taking liraglutide and 11 percent of the participants taking a placebo.
The most commonly reported psychiatric disorders included:
Insomnia
Before starting semaglutide, discuss any history of mental health issues with your healthcare provider.
If you notice any mood changes, experience worsening depression, or have thoughts of self-harm while taking this medication, reach out to a healthcare professional. Your mental well-being is just as important as your physical health, and support is available.
Ozempic carries a black box warning from the FDA (the FDA’s most serious warning). It says that semaglutide has caused thyroid C-cell tumors in rodents after long-term and high dose exposure to the drug. That said, it’s unclear whether semaglutide poses the same risk to humans, and more research is needed to fully understand this.
When it comes to semaglutide side effects, cancer is an unproven risk. Still, it’s helpful to be aware of the symptoms associated with thyroid tumors, which can include:
A mass in the neck
Difficulty swallowing
A persistent hoarse voice
Shortness of breath
In the meantime, if you have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2) — both extremely rare types of thyroid tumors — your medical provider will probably encourage you to avoid using semaglutide medications.
You might wonder how the side effects of semaglutide for weight loss compare to those of tirzepatide medications like Mounjaro® and Zepbound®, both made by Eli Lilly. Like semaglutide, tirzepatide is used to treat type 2 diabetes and aid weight loss in those with overweight or obesity.
Mounjaro is approved for type 2 diabetes and often prescribed off-label for weight loss. Zepbound is FDA-approved for weight loss in adults with obesity or overweight who have a weight-related condition.
The side effects of semaglutide are quite similar to those of tirzepatide, as the drugs work similarly. Both target the GLP-1 receptor, but tirzepatide also targets the insulinotropic polypeptide (GIP) receptor, making it a GIP/GLP-1 receptor agonist.
By mimicking both hormones, tirzepatide helps reduce appetite and food intake, promoting weight loss, as noted in Eli Lilly-sponsored studies.
Common side effects for both semaglutide and tirzepatide include nausea and diarrhea, which can be more pronounced at higher doses. Over five percent of people report these symptoms with 2 milligrams or less of semaglutide, while up to 10 percent experience them with tirzepatide.
Also, in a 40-week trial comparing tirzepatide to semaglutide in individuals with type 2 diabetes, those on tirzepatide lost more weight. But the study also found that five to seven percent of tirzepatide users experienced serious side effects, compared to three percent of semaglutide users.
Yes, semaglutide is generally considered safe for long-term use. Like any medication, it may come with potential side effects and risks. But for many individuals struggling with overweight and obesity, the benefits of losing weight with semaglutide often outweigh those risks.
A comprehensive review of clinical trials involving semaglutide — specifically the 2.4 mg dose used for Wegovy — highlighted that one of the drug’s significant advantages is its effectiveness for long-term weight management.
Though more extensive research is still needed, a study conducted by Novo Nordisk over four years suggests that Wegovy is safe for long-term use.
While compounded semaglutide hasn’t been FDA-approved, compounded drugs from state-licensed pharmacies that stick to the FDA’s Current Good Manufacturing Practice (CGMP) guidelines are considered safe.
The compounded semaglutide available on the Hers platform has the same active ingredient found in Ozempic and Wegovy. And it’s produced in FDA-regulated compounding pharmacies.
It’s possible to regain some of the weight you lost while taking semaglutide once you stop treatment.
A Novo Nordisk study included 2,000 participants with obesity or overweight and a weight-related health condition (excluding type 2 diabetes) who were given a 2.4 mg dose of semaglutide for 68 weeks. They were examined after stopping the medication and healthy lifestyle changes.
The findings showed that, on average, participants regained two-thirds of the weight they’d lost within a year of stopping both the medication and their healthy habits.
This may seem discouraging, but keep in mind that weight regain often happens when people don’t maintain healthy lifestyles.
By focusing on nutritious meals, including an emphasis on protein intake and regular exercise, you can significantly improve your chances of keeping the weight off. Staying committed to a healthy lifestyle can make a big difference in your long-term journey.
All these semaglutide side effects can sound overwhelming. But remember, they’re pretty rare — the severe ones, at least — and this medication is considered safe. Here’s what else to keep in mind:
The most common side effects of semaglutide are gastrointestinal. They’re often temporary and usually subside over time.
There are potential long-term side effects of semaglutide. These are rare. They include pancreatitis, acute kidney injury, gallbladder problems, increased heart rate, diabetic retinopathy, mental health issues, and thyroid cancer.
Semaglutide subcutaneous injections are recommended as a long-term weight management treatment. They’re designed to help people lose and keep off weight. More long-term research is needed, but studies spanning four years indicate the drug’s safety.
The benefits of semaglutide may outweigh its risks. Semaglutide can help you lose weight. So if you have overweight or obesity, the drug might improve your health and quality of life in many ways, outweighing potential long-term risks.
Stay informed about the potential risks of any drug you’re taking. If you have any concerns, discuss them with your healthcare provider. They can help determine if semaglutide is right for you, answer questions, and talk through any of your worries.
Also, other options are available. Take our free online weight loss assessment to find out which weight loss medications could work best for you.
This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.
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