How to Manage Side Effects on CagriSema

How to Manage Side Effects on CagriSema

Starting a new medication on your health journey is a significant step, and it's natural to have questions about what to expect. CagriSema, an investigational medicine that combines the actions of cagrilintide and semaglutide, is being studied for its potential in weight management and type 2 diabetes. Novo Nordisk submitted it to the US FDA for weight management in December 2025; at the time of our October 2026 review it had not been approved in the US or EU, so outside clinical trials it should not be available. Products sold online as "CagriSema" or cagrilintide are not approved medicines, and the FDA states that cagrilintide cannot be used in compounding under US federal law. Like any medication, it can have side effects. Understanding them is key to a smooth and successful experience.

This guide provides a clear overview of common and serious side effects, tips for managing them, and guidance on when to connect with your clinician. The goal is to empower you with information, not to replace the essential advice of your medical team. Consult your healthcare provider before starting any medication.

How CagriSema Works

To understand the side effects, it helps to know a little about how the medication works. CagriSema is a combination of two different types of drugs:

• Semaglutide: A GLP-1 receptor agonist that helps regulate appetite and food intake by targeting areas of the brain involved in hunger. It also slows down how quickly your stomach empties, helping you feel full for longer.
• Cagrilintide: An amylin analog that also works to reduce appetite and slow stomach emptying, complementing the effects of semaglutide.

Because both components primarily affect the digestive system and brain, most of the common side effects are gastrointestinal.

Common Side Effects: What to Expect and How to Cope

The most frequently reported side effects of medications like CagriSema are mild to moderate and often occur when you first start the treatment or increase your dose. For many people, these effects lessen as their body adjusts over time.

Nausea

Nausea is the most common side effect. In the REDEFINE 1 trial, nausea was reported by 55% of people on CagriSema compared with 12.6% on placebo, and gastrointestinal side effects overall by 79.6% compared with 39.9%. It often feels like a mild, lingering queasiness, especially after eating.

What might help:

• Eat Smaller, More Frequent Meals: Overly full feelings can trigger nausea. Instead of three large meals, try five or six smaller ones throughout the day.
• Choose Bland Foods: Stick to simple foods like toast, rice, bananas, and crackers, especially if you're feeling queasy. Avoid greasy, spicy, or heavily processed foods.
• Eat Slowly: Take your time with meals and chew your food thoroughly. This gives your body more time to signal fullness and can aid digestion.
• Stay Hydrated: Sip water, clear broths, or electrolyte drinks throughout the day.

Diarrhea or Constipation

Changes in bowel habits are also common. You might experience either diarrhea or constipation as your digestive system adapts to the medication.

What might help for diarrhea:

• Focus on Hydration: Diarrhea can lead to dehydration, so it's crucial to drink plenty of fluids.
• Try the BRAT Diet: Bananas, rice, applesauce, and toast are low in fiber and can help make your stool firmer.

What might help for constipation:

• Increase Fiber Slowly: Incorporate high-fiber foods like fruits, vegetables, and whole grains into your diet.
• Drink Plenty of Water: Adequate hydration is essential for keeping things moving.
• Stay Active: Gentle physical activity, like walking, can stimulate bowel function.

Vomiting or Burping

Some people may experience vomiting, particularly during the initial dose-escalation phase (26.1% on CagriSema vs 4.1% on placebo in REDEFINE 1). Increased burping or reflux can also occur due to the slower stomach emptying.

What might help:

• Avoid Lying Down After Eating: Stay upright for at least 30 minutes after a meal to help prevent reflux.
• Identify Trigger Foods: Pay attention to whether certain foods, like those high in fat or acid, make your symptoms worse.
• Communicate with Your Provider: If vomiting is frequent or severe, it's important to contact your clinician, as it can lead to dehydration.

Decreased Appetite and Fatigue

A reduced appetite is an intended effect of the medication, but it’s important to ensure you’re still getting adequate nutrition. You might also feel more tired than usual, especially at the beginning of treatment.

What might help:

• Prioritize Nutrient-Dense Foods: Since you may be eating less, focus on making every bite count. Choose foods rich in protein, vitamins, and minerals.
• Listen to Your Body: Rest when you feel tired and don't push yourself too hard. Ensure you are getting enough sleep.

Will Side Effects Improve Over Time?

For the vast majority of people, yes. The body needs time to adapt to a new medication. The gastrointestinal side effects are typically most noticeable during the first few weeks or after a dose increase. As your body adjusts, these symptoms often become much milder or disappear completely.

The gradual dose-escalation schedule is specifically designed to help manage this adjustment period. By starting with a low dose and increasing it slowly over several weeks or months, your body has a chance to get used to the medication, which can minimize the intensity of side effects.

Serious but Less Common Side Effects

While most side effects are manageable, it's important to be aware of the signs of more serious, though rare, potential issues. If you experience any of the following, you should contact your healthcare provider or seek medical attention immediately.

• Pancreatitis: Symptoms include severe, persistent pain in your stomach area (abdomen) that may radiate to your back. This pain may or may not be accompanied by vomiting. Get urgent medical help.
• Gallbladder Problems: This can include gallstones or gallbladder inflammation. Watch for pain in your upper abdomen, fever, nausea, vomiting, or yellowing of the skin or eyes (jaundice).
• Kidney Problems: Diarrhea, nausea, and vomiting can cause a loss of fluids (dehydration), which may worsen kidney function, especially in people with pre-existing kidney issues.
• Low Blood Sugar: If you have type 2 diabetes and also take insulin or a sulfonylurea, the risk of low blood sugar is higher. Watch for shakiness, sweating, confusion or a fast heartbeat.
• Changes in Vision: Semaglutide has been linked to worsening diabetic eye disease in people with type 2 diabetes. Report any change in vision.
• Serious Allergic Reaction: Signs include swelling of your face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; or a very rapid heartbeat.
• Risk of Thyroid C-cell Tumors: In studies with rodents, semaglutide caused thyroid tumors, including a type of thyroid cancer. It is not known if this happens in people. You should not use this medication if you or any of your family have ever had medullary thyroid carcinoma (MTC) or if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Also tell your trial team or doctor if you are pregnant or planning a pregnancy, and tell your anaesthetist before any surgery or sedation, because medicines that slow stomach emptying can raise the risk of food being inhaled under anaesthesia.

Your Partnership with Your Provider

Open and honest communication with your healthcare team is the most important part of managing your treatment. They are your best resource for guidance and support.

Be sure to talk to your clinician if:

• Side effects are severe or don't go away.
• You are struggling to eat or drink enough.
• You are considering stopping the medication or changing your dose. Do not change or skip doses without their advice.

Your provider can offer personalized strategies, adjust your treatment plan if necessary, and ensure you are using the medication safely and effectively as a tool to support your health goals.

Every person's experience is unique, and being informed helps you navigate your journey with confidence. Consult your healthcare provider before starting any medication.

Sources

1. ClinicalTrials.gov: A Study to Compare CagriSema and Semaglutide in People With Overweight or Obesity (REDEFINE 1). https://classic.clinicaltrials.gov/ct2/show/NCT05567796
2. Novo Nordisk: Novo Nordisk successfully completes phase 2 trial with CagriSema in people with type 2 diabetes. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=165830
3. Wegovy (semaglutide) US Prescribing Information and Medication Guide. https://www.novo-pi.com/wegovy.pdf
4. Novo Nordisk announcement on CagriSema NDA submission, with REDEFINE 1 and 2 safety data (December 18, 2025). https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916470
5. MedlinePlus: Semaglutide Injection. https://medlineplus.gov/druginfo/meds/a618008.html
6. FDA: FDA's concerns with unapproved GLP-1 drugs used for weight loss. https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss