GLP-1 Side Effects: What Symptoms Do GLP-1s Cause?

GLP-1s, also known as glucagon-like peptide-1s, are natural gut hormones that the body releases after eating. They help regulate appetite, control blood sugar, and provide essential health benefits that the body needs to function properly. In recent years, artificial GLP-1s, known as GLP-1 RAs, have come on the market to assist with type 2 diabetes management, but they’re also popular for assisting in weight loss and weight management. As with any drug, GLP-1 RAs have known side effects that are common among people taking them.

If you’re interested in starting a GLP-1 medication or have recently started taking one, it’s important to be aware of the side effects. For that reason, here is what you need to know about GLP-1 side effects and what they mean for your body.

What are GLP-1 Receptor Agonists?

GLP-1 receptor agonists, also known as GLP-1 RAs or just GLP-1s, are a class of medications that mimic the effects of the GLP-1s your body naturally produces. These drugs are a type of anti diabetic drugs and were originally developed to help manage type 2 diabetes symptoms, as they can help moderate blood sugar. However, in recent years, GLP-1 RAs have also become popular as a weight loss drug for people who don’t have diabetes. In addition to diabetes, some GLP-1 RAs are FDA-approved to treat obesity.

How GLP-1 RAs Work

GLP-1 RAs are able to mimic natural GLP-1s that your body produces after eating. They operate in four main ways:

1. GLP-1 RAs bind to GLP-1 receptors on pancreatic beta cells, which triggers insulin release, especially in people who do not produce enough insulin naturally. This process helps lower blood sugar and improve glycemic control by facilitating glucose uptake into tissues.
2. GLP-1 RAs inhibit the release of glucagon, a hormone that raises blood sugar levels.
3. GLP-1 RAs slow down the stomach’s emptying process, which prolongs the feeling of fullness and reduces calorie intake.
4. GLP-1 RAs signal the brain to suppress appetite and increase satiety, leading to reduced food intake.

These mechanisms provide beneficial effects for people with type 2 diabetes.

Available GLP-1 RAs

Currently, there are six different types of FDA-approved GLP-1 RAs on the market.

1. Dulaglutide (Trulicity): A weekly injection intended for type 2 diabetes management.
2. Exenatide (Byetta): A twice-daily injection intended for type 2 diabetes management.
3. Liraglutide (Victoza, Saxenda): A weekly injection that can be used for both type 2 diabetes management and as a weight loss drug.
4. Lixisenatide (Adlyxin): A once-daily injection intended for type 2 diabetes management.
5. Semaglutide (Ozempic, Wegovy, Rybelsus): Either a weekly injection or a daily pill that can be used for both type 2 diabetes and as a weight loss drug.
6. Tirzepatide (Mounjaro, Zepbound): A weekly injection that can be used for both type 2 diabetes management and weight loss. Tirzepatide is also the only medication that is a combination of GLP-1 RAs and glucose-dependent insulinotropic polypeptides (GIP).

These FDA-approved medications have been evaluated in multiple clinical trials for both diabetes and weight loss indications.

GLP-1 RA Side Effects

GLP‑1 receptor agonists are generally well tolerated, but it’s important to understand their side effect profile. Most people experience gastrointestinal symptoms as adverse effects early on. These symptoms—such as nausea, vomiting, diarrhea, and constipation—are common, dose-dependent, and may have an increased incidence with higher doses. They tend to subside as the body adapts, especially when dosing is increased slowly.

On the flip side, although rare, some users may face more serious adverse events or negative effects. These include pancreatitis, gallbladder problems, acute kidney injury due to dehydration, gastroparesis, and changes in vision. Digestive issues are a common complication for people taking GLP‑1 RAs.

Below is a breakdown of what’s most likely to occur versus what’s less common but still important to be aware of for anyone taking GLP‑1 RAs.

Common Side Effects

• Nausea and vomiting
• Diarrhea
• Constipation
• Stomach pain
• Bloating
• Injection site reactions
• Increased heart rate
• Appetite changes
• Weight loss
• Indigestion
• Heartburn
• Headache
• Dizziness
• Fatigue
• Hair loss
• Low blood glucose (hypoglycemia)

Serious Side Effects

• Gallstones
• Gallbladder inflammation
• Acute pancreatitis
• Acute kidney injury
• Gastroparesis
• Bowel obstruction
• Intestinal paralysis
• Exenatide administration has been associated with specific risks, including injection site reactions and rare adverse events.
• Cardiovascular events and cardiovascular outcome results have been evaluated in large trials, with no significant increase in risk observed for GLP-1 RAs.
• Central nervous system side effects are rare but have been reported.
• Diabetic retinopathy

Injection Site Reactions

When using injectable GLP-1 RAs, you may notice reactions around the injection site, such as redness, swelling, or pain. To help avoid reactions around the injection site, follow these tips:

• Rotate injection sites every time you take your medication. If you use your abdomen this week, next week use your thigh, and after that, try your upper arm. Changing the injection site every week can help you avoid skin irritation and pain from repeated injections.
• Clean the injection site before injecting. When you get your prescription from the pharmacy, it should come with disposable alcohol swabs to disinfect the injection site. Make sure you always do this before injecting the medication to reduce the chance of infection.
• Use a cold compress. If you’re prone to pain or discomfort at the injection site, try using a cold pack in the area after injecting to reduce swelling.

When to Seek Medical Attention

There’s a spectrum of severity when it comes to the side effects you may encounter when taking GLP-1 RAs, and it may be confusing to know when to seek medical attention for a side effect. Most side effects from GLP‑1 receptor agonists are mild and temporary. However, get medical help right away if you experience any of the following:

• Severe or persistent vomiting, diarrhea, or dehydration that doesn’t improve, especially with dizziness, rapid heartbeat, or dark urine, as this may affect your kidneys or hydration levels.
• Intense upper stomach pain that radiates to your back, especially if paired with nausea, vomiting, or fever, could signal pancreatitis.
• Sharp right-sided abdominal pain, yellowing of your skin or eyes, or dark urine are signs of possible gallbladder issues.
• Vision changes if you have diabetes. GLP‑1s can sometimes affect diabetic eye health temporarily.
• Allergic symptoms such as swelling of the face or throat, rash, or trouble breathing require emergency care.
• Symptoms of hypoglycemic episodes, such as shakiness, confusion, sweating, or loss of consciousness, especially if you are also taking insulin or sulfonylureas.

When in doubt, or if any symptom interferes with your daily life, reach out to your healthcare provider promptly, or go to an emergency room or urgent care.

5 Tips for Alleviating Side Effect Symptoms

You can help yourself avoid some side effects by making small changes in your lifestyle and how you eat while taking GLP-1 RAs. Losing weight gradually, rather than experiencing rapid weight loss, can help prevent facial changes such as sagging or wrinkles, sometimes referred to as ‘Ozempic face.’ Rapid weight loss, especially in the face, may lead to noticeable cosmetic effects, and in severe cases, plastic surgery might be considered to address these changes. It is important to consult healthcare providers for personalized advice on how to lose weight safely and manage any side effects. Here are some things to consider.

1. Eat Smaller Meals

Taking GLP-1s makes you feel fuller faster, and if you force yourself to eat the same size meals that you’re used to, you can end up feeling nauseous. Try cutting your meals in half and saving one portion for the next time you feel hungry. This can also be a good way to meal prep in advance.

2. Eat Foods that are Gentle on the Stomach

If you’re experiencing nausea, diarrhea, or an upset stomach, try to eat foods that are easier on your stomach. Bland, low-fat, and easily digestible foods like crackers, rice, and bananas can help you avoid these side effects. You can also follow a GLP-1 diet to set yourself up for success when using these medications.

3. Stay Hydrated

Drinking enough water throughout the day can be very helpful if you’re experiencing GLP-1 side effects like vomiting, diarrhea, or constipation. Electrolyte packets sold at grocery stores can also be useful for hydration levels, and they can easily be added to bottled water before drinking.

4. Avoid Triggering Foods

Foods that are spicy, greasy, or fatty can potentially trigger side effects or worsen them. For this reason, it can be helpful to limit these types of foods, as well as alcohol and carbonated drinks, especially if you’re unsure how your body will react while taking a GLP-1 RA.

5. Don’t Lie Down After Eating

Feelings of nausea and heartburn can occur if you lay down too soon after eating a meal. Try to remain upright for at least half an hour after eating to lessen the risk of these feelings.

Be Aware of GLP-1 Side Effects

GLP‑1 receptor agonists can be incredibly effective tools for managing type 2 diabetes and supporting weight loss. These medications are part of a broader class known as incretin based drugs, which have been studied for their effects on pancreatic health, including potential risks like pancreatitis. While side effects are common, especially in the early stages, they’re usually manageable with the right strategies and support. Ongoing research and data presented at major conferences and in meta-analyses continue to inform our understanding of GLP-1 RA safety. Transparency in research, including disclosures of relationships with pharmaceutical companies, is essential to ensure trust and clarity in the information provided. Being aware of both the typical and more serious symptoms helps you stay in control of your health while on this medication.

Whether you’re just starting a GLP‑1 RA or have been taking one for a while, you’re not alone in navigating the journey. Support from a qualified healthcare team can make all the difference, especially when it comes to managing side effects, improving your nutrition, and staying on track with your goals.

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GLP-1 Side Effects FAQ (Frequently Asked Questions)

Can GLP-1 RAs Cause Kidney Disease?

Studies have shown that GLP-1 RAs are generally good for the kidneys. While acute kidney injuries are a known risk of taking them, it’s uncommon and can be prevented in part by staying hydrated. Current evidence shows no known link between GLP-1 RAs and kidney disease.

Do GLP‑1 RAs Offer Health Benefits Beyond Blood Sugar Control and Weight Loss?

Yes, studies suggest they may also help lower blood pressure, improve lipid metabolism, benefit fatty liver, and support heart and kidney health.

Are GLP‑1 RAs Safe to Use During Pregnancy or Breastfeeding?

No, they’re generally not recommended in pregnancy due to potential fetal risks like miscarriages and birth defects, as shown in animal studies. If you become pregnant while using GLP-1 RAs, see your healthcare provider immediately.

Can I Continue My GLP‑1 if I Become Ill?

For mild illness, it’s usually safe to continue. However, if you experience severe GI symptoms, holding the medication temporarily may be advisable. You can typically restart without issues after recovery, but always consult your healthcare provider before starting or stopping your medication. However, typically it’s expected that users of GLP-1s should take the medication either indefinitely or for several years for maximum efficiency.