Semaglutide Side Effects: What You Need to Know Before Starting

Semaglutide has become one of the most talked-about medications in recent years. Sold under brand names like Ozempic and Wegovy, it's gained massive popularity for weight loss and blood sugar management. But before you consider using it, understanding what side effects to expect can make a real difference in your experience.

How Semaglutide Works in Your Body

Semaglutide belongs to a class of drugs called GLP-1 receptor agonists. It mimics a natural hormone your gut produces after eating. When you take semaglutide, it signals your brain that you're full, slows down how fast food leaves your stomach, and helps regulate blood sugar. These effects contribute to weight loss and improved metabolic health.

The same mechanisms that make semaglutide effective also explain many of its side effects. Slowed gastric emptying, for instance, helps you feel satisfied with smaller meals. It can also trigger nausea when your body hasn't adjusted yet.

Common Side Effects Most People Experience

Gastrointestinal symptoms top the list. They're so common that doctors consider them almost expected during the first weeks of treatment.

Nausea

Between 20% and 50% of people taking semaglutide report nausea. It's the single most frequent complaint. Most episodes are mild to moderate and don't last long. Clinical data shows the median duration of individual nausea bouts is around 8 days.

Nausea happens most often when you first start taking the medication or when your dose increases. Your body needs time to adjust. After about 20 weeks of treatment, nausea rates drop significantly for most users.

Vomiting and Diarrhea

Vomiting affects up to 24% of users in clinical trials. Diarrhea hits around 30%. Both tend to be temporary. They peak during the dose escalation phase and usually improve as treatment continues.

Constipation

Here's the other side of the coin. While some people deal with diarrhea, others experience constipation. Up to 24% of users report this issue. Slowed digestion doesn't always mean loose stools. Sometimes everything just moves more slowly through your system.

Stomach Pain and Discomfort

Abdominal pain occurs in about 20% of users. It can range from mild cramping to more intense discomfort. The sensation often relates to how slowly food is moving through your digestive tract. Eating smaller portions usually helps.

Fatigue

Tiredness affects users differently depending on the specific product. Fewer than 5% of Ozempic users report fatigue. Wegovy users see higher rates at around 11%. This difference likely relates to dosing. Wegovy uses higher doses for weight loss purposes.

Reduced caloric intake can also contribute to feeling tired. Your body may need time to adapt to running on less fuel.

Serious Side Effects to Watch For

Most side effects are manageable inconveniences. Some require immediate medical attention. Knowing the difference matters.

Pancreatitis

Inflammation of the pancreas has been observed in people using GLP-1 medications. Symptoms include severe pain in your upper abdomen that may radiate to your back, along with vomiting. The pain usually feels worse after eating.

A meta-analysis covering about 35,000 patients found that semaglutide isn't associated with higher pancreatitis risk compared to placebo. Still, acute cases do occur. If you suspect pancreatitis, stop the medication and contact your doctor immediately.

Gallbladder Problems

Rapid weight loss from any cause increases gallstone risk. Semaglutide is no exception. A 2022 FDA review identified 36 cases of acute cholecystitis linked to GLP-1 medications. Of those, 30 patients needed surgery to remove their gallbladder.

Watch for pain in your upper right abdomen, especially after eating fatty foods. Yellowing of your skin or eyes, fever, and nausea can also signal gallbladder issues.

Kidney Problems

Dehydration from vomiting and diarrhea can stress your kidneys. In some cases, this leads to acute kidney injury. People with existing kidney disease face higher risk.

Patients with stage 3b-4 chronic kidney disease should have their kidney function monitored closely. Adequate hydration becomes especially important when GI symptoms are active.

Thyroid Cancer Risk

Tell your doctor if you notice a lump in your neck, trouble swallowing, or a hoarse voice that doesn't improve.

Gastroparesis: The Stomach Paralysis Concern

This topic deserves special attention because it's generated significant discussion. Gastroparesis means your stomach empties much slower than normal. In severe cases, it's sometimes called stomach paralysis.

Some slowing of gastric emptying is expected and even intentional with semaglutide. That's partly how it works. Problems arise when the slowdown becomes extreme.

Symptoms include severe nausea and vomiting that don't improve over time, feeling full very quickly, bloating, and stomach pain. Most cases improve after stopping the medication, usually within weeks to months. However, some reports describe symptoms persisting for an extended period, and rare cases of permanent gastroparesis have been documented.

"Ozempic Face" and Body Composition Changes

Rapid weight loss affects more than the number on your scale. When you lose weight quickly, you lose both fat and lean mass. Your face can look gaunt, with sunken cheeks and more visible wrinkles. People have nicknamed this "Ozempic face."

Clinical trials show that users lost on average 60% fat and about 39% lean mass. Losing muscle during weight loss isn't unique to semaglutide. It happens with any rapid weight reduction method.

The concern intensifies for adults over 60. Loss of muscle mass at that age raises risk for reduced mobility and impacts quality of life. Maintaining strength becomes harder when you're already dealing with age-related muscle decline.

Mental Health Considerations

The relationship between semaglutide and mental health has been studied extensively. Results paint a complex picture.

Large clinical trials like STEP 1-3 found no increased risk of depression or suicidal thoughts in semaglutide users compared to placebo. Across all four STEP trials, 1% or fewer of participants reported suicidal ideation. Actually, fewer semaglutide users needed mental health evaluation than those taking placebo.

Yet pharmacovigilance studies tell a different story. One analysis found significant signals for anxiety, depressed mood, and suicidality associated with semaglutide use. Individual case reports describe people developing depression about a month after starting treatment, with symptoms resolving after they stopped.

Hair Loss

Semaglutide itself doesn't directly cause hair loss. Clinical trials of Ozempic and Wegovy didn't list it as a side effect. However, the FDA has received over 400 reports mentioning hair loss in patients taking semaglutide or similar medications.

Rapid weight loss triggers a condition called telogen effluvium. Your hair growth cycle gets disrupted, and more hairs than usual enter the shedding phase. Nutritional deficiencies from eating less can make this worse. Iron, zinc, vitamin D, and biotin deficiencies are known triggers.

How to Manage Side Effects

Side effects don't have to derail your treatment. Practical strategies can make a significant difference.

Start Low, Go Slow

Healthcare providers typically begin with the lowest effective dose and increase gradually over months. This approach lets your body adjust and minimizes symptoms. Rushing the dose escalation usually means worse side effects.

Adjust Your Eating Habits

Stay Hydrated Wisely

Drink water throughout the day, but take small sips rather than large amounts at once. Avoid drinking much during meals, as this can make you feel overly full. If vomiting or diarrhea is significant, focus on replacing lost fluids and electrolytes.

Timing Your Dose

Take semaglutide at the same time each day or week, depending on your formulation. Some people find that taking it at night helps them sleep through the worst of the nausea. Others prefer morning dosing. Experiment to find what works for your body.

Natural Nausea Remedies

When to Consider Medication for Side Effects

Over-the-counter options like bismuth subsalicylate (Pepto-Bismol) or dimenhydrinate (Dramamine) help some people. If these don't provide enough relief, prescription anti-nausea medications are available. Ondansetron (Zofran) and metoclopramide (Reglan) are commonly prescribed. Talk to your healthcare provider about what's appropriate for your situation.

Protect Your Muscle Mass

• Aim for 60-90 grams of protein daily while taking semaglutide
• Prioritize resistance training at least 2-3 times per week
• Consider working with a personal trainer or physical therapist
• Don't cut calories more drastically than necessary

Long-Term Safety: What We Know So Far

Clinical trials have followed patients for up to 104 weeks. The STEP 5 trial tracked participants for two years and found that less than 4% stopped due to side effects. Most people tolerated the medication well over extended periods.

Rare complications like gallbladder problems or pancreatitis can occur at any point during treatment. They're not more likely after months of use, but they remain possibilities throughout.

Some side effects can lead to longer-lasting issues. Pancreatitis, vision problems, kidney injury, and skin changes may persist after stopping the medication. For most people, though, stopping semaglutide leads to improvement in GI symptoms.

Because these medications are relatively new, experts acknowledge that long-term effects beyond a few years remain unknown. More data will emerge as millions of people continue using them.

A Note on Compounded Semaglutide

Compounded drugs carry higher risk. They should only be used when FDA-approved options aren't available for a specific patient's needs.

When to Contact Your Doctor

Reach out to your healthcare provider if:

• Nausea or vomiting is severe enough to prevent eating or drinking
• You're showing signs of dehydration (dark urine, dizziness, dry mouth)
• Abdominal pain is intense or doesn't improve
• You notice a lump in your neck or difficulty swallowing
• Your mood changes significantly or you experience depressive symptoms
• Vision problems develop
• Side effects don't improve after several weeks on the same dose

Frequently Asked Questions