Zepbound vs Wegovy: Side Effects, Effectiveness and More!

Introduction

Obesity is a rising global health concern. Global reports show that hundreds of millions of adults have been affected in recent decades. These numbers indicate the magnitude of obesity, which is medically defined as having a body mass index (BMI) of more than or equal to 30 kg/m² in adults. It is a significant lifestyle-related risk factor as obesity increases the odds of osteoarthritis, cardiovascular disease, stroke, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease ([MASLD], a liver condition associated with overweight and diabetes), among many other life-threatening diseases.  

With obesity becoming a major health issue, there is a growing interest in new treatment options. Zepbound (tirzepatide) and Wegovy (semaglutide) are two medicines that have come under the spotlight recently. Wegovy is FDA- and EMA-approved at 2.4 mg weekly for chronic weight management. Zepbound is FDA-approved for obesity (in 2023), but availability and approval may differ across countries (not yet EMA-approved as of 2025). They are both GLP-1 receptor agonists (a substance that acts like the natural human GLP-1 hormone and turns on a receptor in the body). Zepbound is a dual GLP-1/GIP agonist, while Wegovy is a GLP-1 agonist¹. 

Overview of Wegovy and Zepbound

Wegovy and Zepbound are the brand names of medicines approved for chronic weight management. Wegovy contains semaglutide and Zepbound contains tirzepatide. Both are injectables used along with a calorie-deficient diet and regular exercise. The FDA had earlier approved semaglutide and tirzepatide for T2D under the brand names Ozempic and Mounjaro, respectively^2,3. 

Table 1: Overview on Wegovy and Zepbound 

How Wegovy and Zepbound work

Wegovy’s active ingredient, semaglutide, works as a GLP-1 receptor agonist. It lowers blood sugar and promotes weight management by activating GLP-1 receptors in the gut, pancreas, and brain, as follows. 

• Gut: It is believed to slow down stomach emptying through signals sent via the vagus nerve and brain, which help reduce appetite and prolong feelings of fullness. 
• Pancreas: Helps enhance insulin release only when blood glucose is elevated and also helps reduce glucagon levels. This mechanism helps maintain stable blood sugar. 
• Brain: Acts on the hypothalamus (sends signals to control appetite) to curb hunger and food cravings. 

The active ingredient in Zepbound, tirzepatide, is a dual agonist that activates both GLP-1 and GIP receptors.  

• GLP-1 Receptors: Promote weight management by curbing the appetite, slowing digestion, and lowering blood sugar levels by boosting insulin and lowering glucagon levels. 
• GIP receptors: Promote meal-time insulin production and keep beta cells (cells that make insulin) healthy in the long term. 

How the medicines affect appetite, satiety (feeling full), and metabolism: 

GLP-1 agonists like semaglutide and dual agonists like tirzepatide reduce hunger, help to maintain the feeling of being full last longer, and steady blood sugar. They curb appetite through their effect on the brain, slow digestion to boost satiety, and improve insulin balance in the pancreas, thus improving weight control, blood sugar regulation, and metabolic parameters (e.g., lipids, insulin sensitivity, and liver fat reduction). Clinical trials (e.g., SURMOUNT-1 vs STEP) show that tirzepatide generally achieves greater weight loss than semaglutide (~20% vs ~15% body weight) at highest doses^3,4. 

Dosage and Administration of Wegovy and Zepbound

Wegovy

• Dosage and administration: Once weekly, on the same day, with or without meals. It can be injected subcutaneously (under the skin) on the abdomen, thigh, or upper arm. Patients with diabetes should monitor their sugar levels before starting it and during treatment⁵. 
• Dosage escalation schedule: The medicine can be started at 0.25 mg per week for 4 weeks with the dosage increased every 4 weeks based on the titration schedule until the maintenance dose is reached⁵. 

Table 2: Dose escalation schedule 

• Maintenance dose: For metabolic dysfunction–associated steatotic liver disease, it is 2.4 mg once weekly. For conditions like weight management, 2.4 mg once weekly (recommended) or 1.7 mg weekly. 
• Dosage forms and strengths: Prefilled, single-use injection pens available in 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg doses. 
• Missed dose flexibility: 
  • If the next scheduled dose is more than 2 days away, the missed dose may be administered as soon as possible. 
  • If the next scheduled dose is less than 2 days away, the missed dose can be skipped and administration resumed from the following week. 
  •  If two or more doses in a row are missed, the schedule should be restarted with a step-up (dosage escalation) schedule to minimise side effects of the digestive system. 

Zepbound

• Recommended dosage escalation schedule: This should be started at 2.5 mg per week for 4 weeks and the dose increased every 4 weeks in 2.5 mg increments until maintenance dose is reached. The maintenance dose can be 5 mg, 10 mg, or 15 mg once weekly, depending on a person’s response and tolerance⁶. 

Table 3: Dose escalation schedule 

• Recommended maintenance and maximum dosage: For weight reduction and long-term maintenance, 5 mg, 10 mg, or 15 mg; for obstructive sleep apnoea, 10 mg or 15 mg injected subcutaneously once weekly. The maximum recommended dosage is 15 mg. 
• Administration: Subcutaneously once per week.  
• Dosage forms and strengths: Available as a single-use pen or vial in different dose sizes- 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg per 0.5 mL (i.e., drug suspension in 0.5 mL of liquid). 
• Missed dose flexibility: 
  • The medicine should be administered within 4 days, i.e., 96 hours. 
  •  If more than 4 days have passed, skip the missed dose and administer the next dose as per regularly planned schedule. 

Effectiveness of Wegovy vs Zepbound

Evidence from clinical trials: In large clinical trials (STEP trials for semaglutide and SURMOUNT for tirzepatide), adults with overweight or obesity were treated with either Wegovy (semaglutide, up to 2.4 mg weekly) or Zepbound (tirzepatide, up to 10–15 mg weekly). Both medicines supported significant weight management, but participants taking the highest doses of Zepbound tended to lose more weight than those on Wegovy. This benefit was seen in people with and without diabetes. Zepbound had slightly higher rates of nausea, vomiting, and diarrhoea than Wegovy, particularly during dose escalation. 

Apart from clinical trials, some real-world retrospective cohort studies (like one study published in JAMA 2023) also compared the two drugs. These showed similar patterns, but because they relied on clinic records, the data wasn’t perfect. Parameters like the exact timing of weigh-ins, side effect tracking, and patient motivation weren’t always clear, and the participants did not fully represent the whole U.S. 

In the trials, participants with type 2 diabetes had separate, dedicated trials (STEP 2 for Wegovy, SURMOUNT-2 for Zepbound). People with depression could still participate, unless their condition was severe or unstable⁷. 

Average percentage weight loss comparison  

Table 4: Average percentage weight loss comparison 

T2D = Type 2 diabetes 

Factors that may affect the outcomes

• Dose differences: The amount of medicine taken matters. 
• Presence/absence of T2D: People without diabetes show better weight management than those with diabetes. 
• Treatment duration and continuation: Staying on the medication is important; stopping early can lower the medicines efficiency. 
• Underreported side effects: Not all side effects get recorded in regular clinic visits. 
• Insurance/ coverage issues: If insurance doesn’t cover the medicine, some patients cannot afford the higher, more effective doses, or may stop the treatment altogether.  

Zepbound vs Wegovy Side Effects

Wegovy

• Common side effects: Nausea, diarrhoea, vomiting, constipation, abdominal pain, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycaemia in patients with T2D, flatulence, gastroenteritis, gastroesophageal reflux, gastritis (viral), and hair loss⁵.

The side effects associated with Wegovy are discussed in Table 5. 

Table 5: Wegovy side effects (less common but serious risks) 

Zepbound

• Common side effects: Nausea, diarrhoea, vomiting, constipation, abdominal pain, dyspepsia, injection-site reactions, fatigue, hypersensitivity reactions, eructation, hair loss, gastroesophageal reflux disease, flatulence, dizziness, and hypotension⁶. 

Other side effects of Zepbound are discussed in Table 6. 

Table 6: Zepbound side effects (less common but serious risks) 

Both Zepbound and Wegovy have similar side effects but with slight variation. Below is a table comparing side effects of both weight management drugs^5,6. 

Table 7: Comparison between side effects of Wegovy and Zepbound 

Managing side-effects safely 

• Most common side effects: These include nausea, vomiting, diarrhoea, constipation, and tiredness⁸. 
• What helps: 
  • Start with a low dose and increase dosage gradually (as per doctor’s advice). 
  • Eat small, light meals; avoid oily, fried, or spicy food. 
  • Drink plenty of water and eat fibre. 
  • Rest, eat slowly, and stop when feeling full. 

When to call the doctor

Call the doctor in case of: 

• Severe stomach pain 
• Ongoing vomiting or dehydration 
• Yellowing of the skin/eyes 
• Trouble breathing, rash, or swelling 

Most side effects get better with time. Follow the doctor’s plan and check in regularly for optimum results. 

Other Potential Health Benefits

Zepbound

• Obstructive sleep apnoea:  Obstructive sleep apnoea (OSA) is defined as repeated episodes of complete (apnoea) or partial (hypopnoea) obstruction of the upper airway during sleep, leading to intermittent low oxygen levels, fragmented sleep, and increased cardiovascular and metabolic risk⁹.  People with obesity and moderate-to-severe OSA who took tirzepatide in the SURMOUNT-OSA randomised, double-blind, placebo-controlled trials (published NEJM 2024) had significant improvements in their breathing during sleep. The number of apnoea–hypopnoea events dropped more in the Zepbound group than in the placebo group, and about half improved to mild or no OSA. Tirzepatide also helped lower blood pressure, reduce inflammation, and enhance sleep quality. These improvements are thought to be largely mediated by weight loss, rather than a direct effect of tirzepatide on the airway. 
• Metabolic effects: The metabolic effects of tirzepatide primarily include weight loss and appetite regulation, which have been discussed elsewhere. Other metabolic effects, like anti-inflammatory effects, body composition, weight loss maintenance, glycaemic control, and effects on lipid profile, are secondary to weight loss and improved insulin sensitivity. The following section briefly explains these metabolic impacts of tirzepatide¹⁰. 
• Anti-inflammatory effects: Tirzepatide reduces inflammation in heart tissues, lowers oxidative stress, and improves lipid metabolism, which in turn reduces inflammatory markers. It is still unclear whether these benefits come directly from the drug or as a result of weight loss. 
• Body composition: Mostly causes fat reduction, but in the process, lean mass loss also occurs (around ~10.9%). 
• Weight maintenance/weight regain: In one study¹⁰, patients lost about 21% of their body weight after 36 weeks on tirzepatide. Those who stayed on the drug for another 52 weeks lost an additional 5.5%, while those switched to placebo regained about 14%. Overall, 89.5% of people on tirzepatide kept at least 80% of their weight loss, compared to only 16.6% on placebo. This shows tirzepatide may need to be taken long-term to prevent weight regain. (This finding comes from the SURMOUNT-4 withdrawal trial, which lasted 88 weeks.) 
• Glycaemic control: Improved insulin secretion and sensitivity (better post-meal glucose control).  
• Effect on lipid profile parameters: Liver fat decreased by about 8.1%. Tirzepatide improves lipid and liver fat profiles, which may help protect cardiovascular health.  

Wegovy

• Reduction in cardiovascular risk: The SELECT trial (2023, NEJM) showed that semaglutide 2.4 mg weekly reduced major adverse cardiovascular events in adults with overweight or obesity and established cardiovascular disease, without diabetes. It lowered appetite and improved weight, lipid metabolism, and inflammation. In SELECT, participants did not have diabetes, so the glucose-lowering effect was not the main reason of benefit. The cardiovascular protection is mostly due to weight loss and improved heart and metabolic health. Evidence from the trial showed fewer cardiovascular events and better outcomes compared to placebo. Common side effects included nausea, vomiting, and diarrhoea, with less common risks such as gallbladder problems and pancreatitis. Diabetic retinopathy worsening was observed in T2D trials (e.g., SUSTAIN-6), not in the non-diabetic SELECT population. However, the benefits were only seen while on treatment and cost remained a barrier since it was not PBS-listed (listed by Pharmaceutical Benefits Scheme – an Australian government program that helps people afford medicines)¹¹. 

Why additional benefits may influence the choice

Many people living with obesity also deal with other health conditions, so choosing a medication that addresses more than one issue can improve overall health and reduce the need for multiple treatments. Wegovy has been shown to lower the risk of heart attack and stroke and may also support certain liver conditions. It may also be the preferred medicine in individuals at high risk of T2D.^1,2 Zepbound, on the other hand, can help improve obstructive sleep apnoea, a condition where breathing repeatedly stops during sleep⁶. For this reason, it is important to consider not only how much weight can be lost but also the added health benefits each treatment may provide. 

Eligibility for Wegovy and Zepbound

The following table lists the eligibility criteria for both Wegovy and Zepbound^5,6: 

Table 8: Eligibility for Wegovy and Zepbound 

Cost of Wegovy and Zepbound

Wegovy is available in pharmacies across India (imported)from the end of June 2025, but Zepbound has not yet been introduced in India. Below is the price list of Wegovy across different doses. 

Table 9: cost per dose for Wegovy (imported) 

Factors that affect the cost 

• Dosage: As seen in the table above, higher dosages cost more. 
• Brand availability: Since these are not manufactured locally, imported pens are pricy. 
• Imports: Shipping fees, import duties, and limited suppliers drives up the cost. 

Accessibility challenges in India (Only Wegovy)

• Insurance does not cover obesity drugs in India; therefore, patients must pay out of pocket. 
• Even patients who can afford it may struggle with irregular supplies (as imports are inconsistent). 

Why affordability matters in long term use

• Both drugs are long-term treatments, so stopping suddenly leads to weight regain. 
• These medications are expensive, so many patients stop early. 
• Affordability is important so that people can stay on the treatment and also improve related conditions like diabetes and heart disease. 

Switching from Wegovy to Zepbound or Vice Versa

• When switching might be considered: 
  • Current medicine is not lowering blood sugar enough^12,13. 
  • Not enough weight loss is seen. 
  • Side effects are hard to manage. 
  • Cost and convenience. 
• Why it must be supervised by a doctor 
  • Switching involves timing the last dose of one medicine and the first dose of the new one to avoid overlaps or gaps. 
  • Based on a person’s situation, doctors decide whether to start at the lower dose or move directly to maintenance dose. 
  • Only a doctor can manage possible risks like low blood sugar (GLP-1/GIP agonists alone do not usually cause hypoglycaemia. The risk occurs only if combined with insulin or sulfonylurea) or stomach side effects. 
• Key precautions to keep in mind: 
  • Do not overlap medications. Since both semaglutide and tirzepatide are weekly injections with long half-lives (~1 week), the new drug is usually started when the next dose would have been due. Gaps longer than 1–2 weeks may cause return of appetite and weight gain. 
  • If the medicine is switched because of stomach problems, wait until the problems settle before starting the new drug. 
  • If switching for other reasons (like cost or convenience), the new drug is started out at a low dose and increased slowly, even if the patient was already on a higher dose of the previous drug. Direct switching to a maintenance dose raises the risk of intolerance. 
  • Side effects (like nausea or stomach upset) are usually mild; however, must be reported right away if they become severe. 
  • Follow-up is typically every 4–8 weeks during dose titration. Weekly or biweekly monitoring is not standard unless the patient has type 2 diabetes and is also on insulin or sulfonylurea. 

Conclusion

Wegovy and Zepbound are both promising medicines used to manage overweight and obesity. The key difference is that while both act on GLP-1 receptors, Zepbound also targets GIP receptors. The choice between them depends entirely on a patient’s health needs. It is advisable to research both medicines and consult a doctor before making a decision. Regular check-ups and monitoring of symptoms are vital. It is important to remember that there is no solution that may fit everyone. What works best often depends on health history, side effect tolerance, availability, and cost. 

The safest step is to consult a qualified healthcare professional before making any decision. A doctor can assess medical history, existing health conditions, and long-term goals to recommend the most suitable treatment. 

Frequently Asked Questions (FAQs)

References

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2. Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med. 2022;70(1):5-13. doi:10.1136/jim-2021-001952. Available from:https://pmc.ncbi.nlm.nih.gov/articles/PMC8717485/ 
3. Farzam K, Patel P. Tirzepatide. [Updated 2024 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK585056/ 
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6. Eli Lilly and Company. Zepbound (tirzepatide) injection, for subcutaneous use: U.S. prescribing information. U.S. Food and Drug Administration, Center for Drug Evaluation and Research; November 2023. Application No. 217806. Available from:https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217806Orig1s020lbl.pdf 
7. Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. 2024;184(9):1056-1064. doi:10.1001/jamainternmed.2024.2525. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11231910/ 
8. Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J, et al. Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus. J Clin Med. 2022;12(1):145. Published 2022 Dec 24. doi:10.3390/jcm12010145. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9821052/ 
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10. Sara Sokary, Hiba Bawadi, The promise of tirzepatide: A narrative review of metabolic benefits, Primary Care Diabetes,Volume 19, Issue 3,2025,Pages 229-237,ISSN 1751-9918, Available from: https://www.primary-care-diabetes.com/article/S1751-9918(25)00081-6/fulltext 
11. Semaglutide for cardiovascular risk reduction in people who are overweight or have obesity without diabetes (new indication). AustPrescr. 2025;48(3):107-108. doi:10.18773/austprescr.2025.024. Available from:https://pmc.ncbi.nlm.nih.gov/articles/PMC12187477/ 
12. Jabbour S, Paik JS, Aleppo G, Sharma P, Gomez Valderas E, Benneyworth BD. Switching to Tirzepatide 5 mg From Glucagon-Like Peptide-1 Receptor Agonists: Clinical Expectations in the First 12 Weeks of Treatment. EndocrPract. 2024;30(8):701-709. doi:10.1016/j.eprac.2024.05.005. Available from:https://www.endocrinepractice.org/article/S1530-891X(24)00515-9/fulltext 
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