Starting a GLP-1 medication like semaglutide or tirzepatide comes with questions about side effects. What should you expect? Which symptoms are normal? When should you worry? These are some of the most common concerns providers hear from patients beginning treatment with Ozempic, Wegovy, Mounjaro, or Zepbound.

The reality is that most people experience some side effects when starting GLP-1 therapy. This does not mean the medication is dangerous or wrong for you. It reflects how your body adapts to changes in digestion and appetite signaling. Understanding what is normal, what is manageable, and what requires medical attention helps you navigate treatment with confidence rather than anxiety.

This article covers the most common GLP-1 side effects, why they happen, how to manage them, and the warning signs that require immediate attention. It also addresses how long side effects last and what you can do to minimize discomfort during the adjustment period.

Why GLP-1 Medications Cause Side Effects

GLP-1 receptor agonists work by mimicking your body's natural GLP-1 hormone. This hormone does several things: it slows how quickly food leaves your stomach, signals fullness to your brain, improves insulin sensitivity, and reduces appetite. These mechanisms make GLP-1 medications highly effective for weight loss and blood sugar control. They also explain why side effects happen.

When digestion slows, your stomach feels fuller longer. This is therapeutic, but it can also cause nausea, bloating, and changes in bowel patterns. Your body needs time to adjust to this new pace of digestion. Most people adapt within four to eight weeks, though some symptoms may return temporarily after dose increases.

The intensity of side effects varies from person to person. Factors that influence severity include your starting dose, how quickly you increase doses, your individual sensitivity to the medication, and whether you are combining it with other medications. People who start low and increase slowly tend to tolerate the medication better than those who escalate quickly.

The Most Common GLP-1 Side Effects

Nausea

Nausea is the most frequently reported side effect of semaglutide and tirzepatide. It affects roughly 30 to 50 percent of people starting treatment, particularly during the first few weeks. The nausea typically peaks two to three days after your weekly injection and improves as the week progresses. For most people, nausea becomes much less intense after four to six weeks as the body adjusts.

Nausea happens because food moves through your stomach more slowly than usual. Your brain interprets this delayed emptying as fullness, which can register as nausea. The sensation is usually manageable and does not prevent most people from continuing treatment.

What helps with nausea? Eating smaller, more frequent meals works better than three large meals. Many people find success with four to five small meals throughout the day. Avoiding greasy, fatty, or spicy foods during the adjustment phase reduces nausea for most people. Eating slowly and stopping when you feel satisfied rather than full also makes a significant difference. 

Ginger is one of the few natural remedies with good evidence for reducing nausea. Ginger tea, ginger candies, or ginger capsules can provide relief. Some people also find that taking vitamin B6 supplements helps, though the evidence is less clear. If nausea is severe or persistent, your provider can prescribe anti-nausea medications like ondansetron, which is safe to use with GLP-1 medications and often very effective. Check out our nausea medications here. 

Timing your injection can also help. Some people inject at night so they sleep through the peak nausea period. Others prefer morning injections. Finding what works for your schedule and symptom pattern takes some trial and error.

Digestive Changes

Changes in bowel habits are common with GLP-1 therapy. Some people experience diarrhea, particularly in the first few weeks. Others develop constipation, which can persist longer term due to the slowed digestive process. Some people alternate between both.

Diarrhea usually resolves on its own within the first month. During this time, sticking to bland, easy-to-digest foods helps. The BRAT diet (bananas, rice, applesauce, toast) can be useful temporarily. Avoiding dairy, caffeine, and high-fat foods while your digestive system adjusts often reduces diarrhea. Staying hydrated is especially important if you are experiencing loose stools. If diarrhea persists beyond a week or becomes severe, contact your provider.

Constipation is more common as a long-term side effect because the medication continuously slows digestive motility. It also results from eating less food, which means less bulk moving through your intestines. Managing constipation requires a multi-pronged approach. Drinking plenty of water is essential. Most people need at least 64 ounces daily, sometimes more. Increasing fiber gradually helps, but adding too much fiber too quickly can worsen bloating. Aim for 25 to 30 grams of fiber daily from food or supplements. Staying physically active, even with just daily walks, supports regular bowel movements. Magnesium supplements can be helpful for both constipation and sleep quality.

If these measures are not enough, over-the-counter options like polyethylene glycol (Miralax) or docusate (Colace) are safe for regular use. Your provider can recommend the best approach for your situation. Check out our GI medications here. 

Bloating and gas often accompany the changes in digestion. These symptoms result from food spending more time in your digestive tract. Reducing carbonated beverages, limiting beans and cruciferous vegetables initially, and eating smaller portions all help minimize bloating. Simethicone (Gas-X) can provide relief when needed.

Decreased Appetite and Food Aversion

The dramatic reduction in appetite is actually how GLP-1 medications work for weight loss, but the intensity surprises many people. You may feel completely disinterested in food, experience aversions to foods you previously enjoyed, or feel full after just a few bites. Some people describe feeling "food neutral" or forgetting to eat entirely.

While decreased appetite supports weight loss, you still need adequate nutrition. The challenge is meeting your nutritional needs when food feels unappealing or you have little hunger. Focusing on protein-rich foods first ensures you get essential nutrients even when eating less overall. Protein shakes, Greek yogurt, eggs, and lean meats are practical options when solid food is unappealing.

Many people need to set reminders to eat because natural hunger cues decrease significantly. Tracking your food intake, at least initially, helps ensure you are meeting minimum calorie needs of 1,200 to 1,500 per day and protein goals of 60 to 80 grams daily. These minimums protect your muscle mass and metabolic health.

Fatigue

Fatigue is common during the first few weeks of GLP-1 therapy. It happens for several reasons. Your body is adjusting to consuming fewer calories than usual. Your metabolism is shifting. Your energy intake may not yet be optimized for your new appetite level. The result is often a feeling of low energy or tiredness that can be frustrating.

The good news is that fatigue typically improves significantly after four to six weeks. During the adjustment phase, ensuring adequate protein intake, staying hydrated, getting enough sleep, and maintaining light physical activity all help manage fatigue. A daily multivitamin can help cover nutritional gaps while your eating patterns stabilize.

If fatigue persists beyond six to eight weeks or feels extreme, it is worth investigating further. Your provider may want to check your thyroid function, iron levels, vitamin B12, vitamin D, and blood sugar to rule out deficiencies or other issues. Persistent fatigue is not something you should just tolerate long term.

Headaches

Headaches affect roughly 10 to 15 percent of people starting GLP-1 therapy, usually during the first two weeks. These are typically mild and respond well to over-the-counter pain relievers like acetaminophen or ibuprofen. Staying well hydrated often prevents headaches or reduces their intensity. For most people, headaches resolve within the first month and do not return.

Injection Site Reactions

Some people develop mild reactions at the injection site, including redness, itching, or small bumps. These reactions are usually minor and resolve within a few days. Rotating injection sites (abdomen, thigh, upper arm) helps prevent repeated irritation in one area. Allowing your medication to reach room temperature before injecting can also reduce injection site discomfort.

Heartburn and Acid Reflux

Slowed stomach emptying can cause or worsen acid reflux and heartburn. If you are prone to these symptoms, they may become more noticeable on GLP-1 therapy. Avoiding lying down within three hours of eating, elevating the head of your bed, reducing trigger foods like caffeine and alcohol, and taking antacids or proton pump inhibitors can all help manage reflux symptoms.

Side Effects That Require Immediate Medical Attention

While most side effects are manageable and temporary, certain symptoms require urgent evaluation. Knowing these warning signs helps you respond appropriately if they occur.

Severe Abdominal Pain

Sharp, severe, or persistent abdominal pain, particularly if it radiates to your back or is located in your upper right abdomen, requires immediate medical attention. This type of pain could indicate pancreatitis or gallbladder inflammation, both of which are rare but serious complications of GLP-1 therapy.

Pancreatitis typically presents as severe upper abdominal pain that does not improve with position changes and may be accompanied by persistent nausea, vomiting, fever, or rapid heart rate. If you experience these symptoms, stop your medication and seek immediate medical care.

Gallbladder problems can develop during rapid weight loss. Symptoms include sharp pain in the upper right abdomen, pain after fatty meals, yellowing of the skin or eyes, clay-colored stools, or dark urine. These symptoms warrant prompt evaluation.

Persistent Vomiting

Occasional nausea is expected, but persistent vomiting that prevents you from keeping down food or liquids for more than 24 hours is concerning. This can lead to dangerous dehydration and electrolyte imbalances. Signs of dehydration include extreme thirst, dark urine, dizziness when standing, confusion, and decreased urination.

Persistent vomiting may also indicate severe gastroparesis, a condition where the stomach becomes unable to empty properly. While rare, this is a serious complication that requires medical evaluation and may necessitate temporarily stopping the medication.

Allergic Reactions

True allergic reactions to GLP-1 medications are uncommon but require emergency care. Symptoms include difficulty breathing, throat tightness or swelling, severe widespread rash or hives, facial swelling, rapid or irregular heartbeat, or severe dizziness. These reactions typically occur within hours of an injection. If you experience any of these symptoms, call 911 immediately.

Changes in Vision

Any sudden changes in vision, particularly affecting one eye, should be reported to your provider promptly. While vision changes are rare, people with diabetes should be especially vigilant, as rapid improvements in blood sugar can temporarily affect diabetic retinopathy.

Signs of Low Blood Sugar

If you are taking GLP-1 medications in combination with insulin or sulfonylureas, you have an increased risk of low blood sugar. GLP-1 medications alone rarely cause hypoglycemia, but the combination with these other medications can. Watch for shakiness, sweating, rapid heartbeat, dizziness, confusion, or extreme hunger. If you experience these symptoms, check your blood sugar if possible, consume 15 grams of fast-acting carbohydrates, and contact your provider about adjusting your diabetes medications.

Thyroid Symptoms

GLP-1 medications carry a warning about potential thyroid tumors based on animal studies, though this has not been observed in humans. Nonetheless, if you notice a persistent lump or swelling in your neck, persistent hoarseness, difficulty swallowing, or persistent shortness of breath, these symptoms warrant evaluation. Do not take GLP-1 medications if you have a personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2.

Mental Health Changes

Some people report mood changes, increased anxiety, or depression while taking GLP-1 medications, though direct causation is not clearly established. If you experience persistent sadness, loss of interest in activities, suicidal thoughts, or significant anxiety, contact your healthcare provider immediately. Your mental health is as important as your physical health during treatment.

How Long Do Side Effects Last?

The timeline of side effects follows a predictable pattern for most people. The first two weeks are typically the most challenging. Nausea peaks, fatigue is most noticeable, and appetite changes feel most dramatic. This is the adjustment period when your body is learning to function with slower digestion and different hunger signals.

By weeks three and four, most people notice improvement. You develop strategies for managing remaining symptoms. Nausea becomes less intense or less frequent. Energy levels begin recovering. You start feeling more like yourself again, though with a substantially reduced appetite.

Between weeks five and eight, the majority of common side effects diminish significantly. Many people report feeling essentially normal again, though still experiencing the therapeutic effect of reduced appetite. This is the period when treatment starts feeling sustainable rather than challenging.

After each dose increase, you may experience a mini-return of side effects, usually milder than what you experienced initially. These typically last one to two weeks. Each subsequent dose increase tends to be easier than the previous one as your body becomes more adapted to the medication.

Long term, after three or more months on a stable dose, most people have minimal side effects. You may retain some sensitivity to large meals or high-fat foods, and reduced appetite becomes your new normal, but the disruptive symptoms of early treatment generally resolve.

Strategies for Minimizing Side Effects

There are practical steps you can take to reduce the intensity of side effects during the adjustment period.

Starting low and increasing slowly makes a substantial difference in tolerability. There is no benefit to reaching the maximum dose quickly. If side effects are significant, staying at each dose level for six weeks instead of four allows more time for adaptation. Work with your provider to find a titration schedule that balances effectiveness with tolerability.

Meal timing and composition matter more than you might expect. Eating smaller portions more frequently prevents overwhelming your slowed digestive system. Prioritizing protein at each meal supports muscle preservation and satiety. Avoiding high-fat, greasy, or fried foods during the adjustment phase reduces nausea for most people. Eating slowly and putting your utensil down between bites gives your body time to register fullness.

Hydration is one of the simplest and most effective ways to reduce side effects. Aim for at least 64 ounces of water daily, sipped throughout the day rather than consumed in large amounts at once. Many people find they need conscious effort to drink enough because thirst decreases along with appetite. Adequate hydration reduces constipation, fatigue, and headaches significantly.

Physical activity supports digestion and helps manage constipation, but it does not need to be intense. Daily walks, gentle yoga, or light strength training all provide benefits. During the first few weeks when fatigue may be higher, listen to your body and avoid pushing too hard. Movement should feel supportive, not exhausting.

Consider the timing of your injection. Some people do better injecting at night so they sleep through the peak symptom period. Others prefer morning injections. Experimenting with timing can help you find what works best for your schedule and symptom pattern.

Stock your kitchen with easy-to-digest foods before you start treatment. Having Greek yogurt, crackers, bananas, plain chicken, and protein shakes readily available makes it easier to eat well when appetite is low or nausea is present.

When to Contact Your Provider

Your provider wants to hear from you about your experience with GLP-1 therapy. Many people hesitate to reach out, assuming their symptoms are normal or not wanting to bother their provider. However, reporting side effects allows your provider to help you more effectively.

Contact your provider if nausea is severe enough to interfere with work or daily activities. They can prescribe anti-nausea medications or adjust your dose. If fatigue is limiting your ability to function normally, your provider may want to check labs or slow your dose increases. If constipation persists despite hydration and fiber, prescription options are available. If you are struggling to meet minimum nutritional needs, your provider or a dietitian can help you develop strategies.

Severe or persistent symptoms always warrant contact. Vomiting that prevents you from staying hydrated, severe abdominal pain, signs of dehydration, allergic reaction symptoms, or any of the red flag symptoms described earlier require prompt medical attention.

You should also reach out if you are considering stopping the medication due to side effects. In many cases, adjustments to dosing or additional support can make treatment tolerable. Stopping treatment should be a collaborative decision made with your provider's guidance.

What If One GLP-1 Medication Doesn't Work for You?

If you struggle significantly with one GLP-1 medication, you may tolerate a different one better. Semaglutide and tirzepatide have slightly different mechanisms and side effect profiles. Some people who cannot tolerate semaglutide do well with tirzepatide, and vice versa. Daily formulations like liraglutide also exist and may work better for some people.

Alternatively, some people do better on a lower maintenance dose long term rather than pushing to the maximum dose. Weight loss may be slower, but if the lower dose is sustainable and still producing results, that is a reasonable approach.

The Bigger Picture

Side effects are a normal part of starting GLP-1 therapy for most people. They reflect your body's adjustment to changes in digestion and appetite signaling. While the first few weeks can be uncomfortable, the majority of side effects improve significantly with time and proactive management.

Understanding what is normal helps you navigate early treatment with less anxiety. Knowing warning signs helps you recognize when medical attention is needed. Having strategies for managing common symptoms makes the adjustment period more tolerable.

Most people find that side effects become much less of an issue after the first month or two. The medication becomes part of your routine, your body adapts, and the therapeutic benefits continue without the disruptive symptoms of early treatment. Patience, communication with your provider, and realistic expectations make all the difference in successfully navigating this process.

Check Your Eligibility

If you want to learn whether GLP-1 treatment is right for you and receive personalized guidance from providers who understand how to optimize your experience, you can start by completing Mochi's eligibility questionnaire. It only takes a few minutes and helps our clinical team understand your goals and health history. Check your eligibility here.

References

Aroda, V. R., Ahmann, A., Cariou, B., Chow, F., Davies, M. J., Gigante, R., Nauck, M. A., Ørsted, D. D., Lingvay, I., & PIONEER 1 Investigators. (2019). Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the PIONEER trials. Diabetes Care, 42(9), 1595-1603. https://doi.org/10.2337/dc19-0149

Davies, M., Færch, L., Jeppesen, O. K., Pakseresht, A., Pedersen, S. D., Perreault, L., Rosenstock, J., Shimomura, I., Viljoen, A., Wadden, T. A., & Lingvay, I. (2021). Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): A randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet, 397(10278), 971-984. https://doi.org/10.1016/S0140-6736(21)00213-0

Dahl, D., Onishi, Y., Norwood, P., Huh, R., Bray, R., Patel, H., & Rodríguez, Á. (2022). Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: The SURPASS-5 randomized clinical trial. JAMA, 327(6), 534-545. https://doi.org/10.1001/jama.2022.0078

Drucker, D. J., & Nauck, M. A. (2006). The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. The Lancet, 368(9548), 1696-1705. https://doi.org/10.1016/S0140-6736(06)69705-5

Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., & Stefanski, A. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205-216. https://doi.org/10.1056/NEJMoa2206038

Meier, J. J. (2021). Efficacy of semaglutide in a subcutaneous and an oral formulation. Frontiers in Endocrinology, 12, 645617. https://doi.org/10.3389/fendo.2021.645617

Novo Nordisk. (2023). Ozempic (semaglutide) injection prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209637s014lbl.pdf

Novo Nordisk. (2023). Wegovy (semaglutide) injection prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215256s006lbl.pdf

Pratley, R. E., Aroda, V. R., Lingvay, I., Lüdemann, J., Andreassen, C., Navarria, A., & Viljoen, A. (2018). Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): A randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology, 6(4), 275-286. https://doi.org/10.1016/S2213-8587(18)30024-X

Rubino, D. M., Greenway, F. L., Khalid, U., O'Neil, P. M., Rosenstock, J., Sørrig, R., Wadden, T. A., Wizert, A., & Garvey, W. T. (2021). Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: The STEP 8 randomized clinical trial. JAMA, 327(2), 138-150. https://doi.org/10.1001/jama.2021.23619

Sodhi, M., Rezaeianzadeh, R., Kezouh, A., & Etminan, M. (2023). Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA, 330(18), 1795-1797. https://doi.org/10.1001/jama.2023.19574

Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989-1002. https://doi.org/10.1056/NEJMoa2032183

Eli Lilly and Company. (2023). Mounjaro (tirzepatide) injection prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215866s000lbl.pdf

Eli Lilly and Company. (2023). Zepbound (tirzepatide) injection prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217806s000lbl.pdf