The increasing media attention on weight loss and diabetes medications like semaglutide and tirzepatide has led many individuals to seek a better understanding of these treatments. Both medications have gained popularity due to their effectiveness, but understanding their differences and similarities is crucial for informed conversations with a licensed medical provider about whether these medications are right for you. Semaglutide and tirzepatide are injectable medications offering new hope for those struggling with weight management. These medications are part of a new generation of therapies that have revolutionized medical treatment for patients who are struggling to lose weight. Both semaglutide and tirzepatide have shown unprecedented weight loss in patients.
Understanding Semaglutide and Tirzepatide
Semaglutide and tirzepatide are injectable medications initially used for managing type 2 diabetes, with the remarkable and unexpected side effect of significant weight loss. They belong to a class of drugs known as GLP-1 receptor agonists. These medications mimic the action of a hormone called glucagon-like peptide-1 (GLP-1). Semaglutide is a GLP-1 receptor agonist, mimicking a hormone your gut already produces, which helps regulate appetite and blood sugar levels. Tirzepatide is a dual agonist acting on both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. This combination helps lower blood sugar levels after meals and promotes fullness, which can contribute to reduced food intake.
Semaglutide increases insulin secretion, decreases glucagon release, and slows gastric emptying. Tirzepatide, sold under the brand name Mounjaro®, is a dual-action medication that targets both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. This dual action can make tirzepatide more effective in lowering blood sugar levels and promoting weight loss. But the real mechanisms underlying their extraordinary effectiveness in weight loss lie in their effects within the brain.
Semaglutide is marketed under brand names such as Ozempic (for diabetes) and Wegovy (for weight loss). Tirzepatide is a newer medication that combines the actions of GLP-1 and another hormone called glucose-dependent insulinotropic polypeptide (GIP). These benefits only highlight those that have been confirmed through the FDA testing process.
Effectiveness for Weight Management
Both medications are used for weight management, but tirzepatide has shown slightly higher effectiveness. In clinical trials, patients using semaglutide for weight loss achieved an average reduction of 10-15% of their body weight over a year. Tirzepatide users saw even more impressive results, with average weight loss reaching 15-20% of their body weight in some trials. Studies generally report a weight loss of about 15-16% of initial body weight with semaglutide, while tirzepatide can result in a 14-18% reduction.
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A cohort study of adults with overweight or obesity receiving semaglutide or tirzepatide, using electronic health record data linked to dispensing information from a collective of US health care systems, assessed on-treatment weight outcomes. Among 41,222 adults meeting the study criteria (semaglutide, 32,029; tirzepatide, 9,193), 18,386 remained after propensity-score matching. The mean (SD) age was 52.0 (12.9) years, 12,970 were female (70.5%), 14,182 were White (77.1%), 2,171 Black (11.8%), 354 Asian (1.9%), 1,679 were of other or unknown race, and 9,563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5,140 patients (55.9%) receiving tirzepatide and 4,823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%: hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.68-1.84; ≥10%: HR, 2.54; 95% CI, 2.37-2.73; and ≥15%: HR, 3.24; 95% CI, 2.91-3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI, -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). The authors report that use of tirzepatide was associated with significantly greater weight loss than semaglutide. This cohort study reports that individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with semaglutide. Furthermore, consistent treatment effect estimates were observed in subgroups with and without T2D.
Another retrospective cohort study included obese or overweight adults (BMI ≥27 kg/m2) with an incident prescription (index date) for semaglutide or tirzepatide between 13 May 2022 and 1 October 2023. A total of 945 adults were included (semaglutide n = 836, tirzepatide n = 109). Over the 6‐month follow‐up period, patients prescribed tirzepatide experienced significantly greater weight loss compared with semaglutide patients (mean loss 6.6 kg vs. 3.1 kg, p < 0.001, mean percent loss 5.3% vs. 2.7%, p < 0.001). In an unadjusted linear regression analysis, tirzepatide was significantly associated with an additional 2.6% (95% CI −4.0%, −1.3%, p < 0.001) weight loss compared with semaglutide. In patients without diabetes that tirzepatide was associated with an additional 3.6% weight loss (95% CI −5.5%, −1.8%, p < 0.001) relative to semaglutide. Overall, significantly greater proportions of patients prescribed tirzepatide lost >5% (48.6% vs. 26.0%), >10% (22.9% vs. 9.3%) and >15% (10.1% vs. In the subgroup of patients without diabetes (n = 416), patients prescribed tirzepatide experienced a larger loss in body weight compared with those prescribed semaglutide (7.0% vs. 3.4%, p < 0.001). In the population with diabetes (n = 529), the percentage of weight loss was not statistically different between the tirzepatide and semaglutide groups (−3.3% vs. −2.2%, p = 0.30). In this study of patients who were overweight or obese, tirzepatide was associated with greater weight loss over 6 months of follow‐up than semaglutide overall and in patients without diabetes.
Side Effects
Both drugs have common side effects related to the gastrointestinal system. Because both medications slow gastric emptying, they can cause nausea, vomiting, and digestive discomfort. Semaglutide users might experience more pronounced side effects due to its sole GLP-1 action, while tirzepatide’s dual mechanism might result in a different side effect profile. Both medications can cause gastrointestinal side effects, such as nausea, vomiting, and diarrhea. Tirzepatide’s dual-action mechanism may result in a different side effect profile compared to semaglutide, and ongoing studies continue to evaluate these differences. No significant differences in the incidence of gastrointestinal AEs were observed. However, it is essential to consult with a healthcare provider to manage these side effects.
Dosage and Administration
Both semaglutide and tirzepatide are administered via weekly subcutaneous injection. Semaglutide is available as an oral, FDA-approved medication called Rybelsus that is used to treat Type 2 diabetes. It is critical that you work with a licensed medical provider to determine the appropriate dosage schedule for you. The dosing parameters noted in this blog post are general guidelines.
For semaglutide, the dosing typically starts at 0.25 mg per week and gradually increases to 2.4 mg per week for weight loss, titrating every four weeks to minimize side effects. Tirzepatide, branded as Mounjaro for diabetes and ZepBound for weight loss, typically starts at 2.5 mg per week and can increase to 15 mg.
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Factors Influencing Medication Choice
A licensed medical provider will help you decide which medication to use based on several factors, including your medical history, specific health goals, and financial considerations. Individuals with a history of medullary thyroid cancer or certain other conditions should avoid these medications due to potential risks.
If you are not tolerating one medication well, switching to the other is possible but must be managed by a licensed medical provider. It’s not a direct switch, and starting doses may need to be adjusted to avoid adverse effects. Many factors determine which medication is better for you.
Insurance Coverage
Approved specifically for weight loss as Wegovy®, semaglutide is sometimes covered by insurance if we prescribe it for obesity. Since tirzepatide was initially approved for diabetes management, insurance coverage may be more accessible for diabetic patients. Both medications are excellent for managing blood sugar if you have diabetes, but tirzepatide’s dual receptor activation may offer added benefits for glucose control alongside weight loss. Both treatments have gastrointestinal side effects, but you may find that one suits you better than the other. Coverage varies widely, so check with your insurance provider about what may be covered under your plan.
The FDA-approved indications for use of Wegovy (semaglutide, Novo Nordisk) and Zepbound (tirzepatide, made by Eli Lilly) are individuals with obesity - with a BMI of 30 or higher, and individuals with a BMI of 27 who have at least 1 “comorbid” health condition are eligible for (but NOT assured of) insurance-coverage of these medications as part of a comprehensive weight loss plan. “Comorbid condition” means that patients have other health conditions that are either caused by or contributed to by the presence of obesity. High blood pressure, high cholesterol levels, and type-2 diabetes are all conditions that can often result from being overweight or obese. Semaglutide (Wegovy) is already FDA-approved specifically for weight loss in this these populations, as is Zepbound (tirzepatide).
Compounded Versions and FDA Concerns
FDA is aware that some patients and health care professionals may look to unapproved versions of GLP-1 (glucagon-like peptide-1 (GLP-1) receptor agonists) drugs, including semaglutide and tirzepatide, as an option for weight loss. This can be risky for patients, as unapproved versions do not undergo FDA’s review for safety, effectiveness and quality before they are marketed. Compounded drugs should only be used in patients whose medical needs cannot be met by an FDA-approved drug. Patients should obtain a prescription from their doctor and fill the prescription at a state-licensed pharmacy.
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The agency has identified some areas of concern for compounded GLP-1 drugs. FDA is working with its state regulatory partners and will continue to communicate with compounders regarding these concerns. Improper storage during shipping may lead to quality issues, as injectable GLP-1 drugs require refrigeration as indicated in their package inserts. FDA has received complaints that certain compounded GLP-1 drugs have arrived warm or with inadequate ice packs to keep the drug at recommended storage temperatures.
FDA is also aware of compounded drugs that contain false information on the product label and one reported adverse event associated with a product labeled as compounded tirzepatide from a pharmacy that did not actually compound the product.
Dosing concerns with compounded semaglutide and tirzepatide have also arisen, with FDA receiving multiple reports of adverse events, some requiring hospitalization, that may be related to dosing errors associated with compounded injectable semaglutide products.
Retatrutide and cagrilintide cannot be used in compounding under federal law, as these are not components of FDA-approved drugs and have not been found safe and effective for any condition. The agency has issued warning letters to companies distributing active pharmaceutical ingredients, such as retatrutide and certain other GLP-1 drugs.
The agency is aware that some semaglutide products sold by compounders may be the salt forms. These salt forms, including semaglutide sodium and semaglutide acetate, are different active ingredients than are used in the approved drugs. The agency does not have information on whether these salts have the same chemical and pharmacologic properties as the active ingredient in the approved drug, and we are not aware of any lawful basis for their use in compounding.
FDA has received reports of adverse events related to compounded versions of semaglutide and tirzepatide. However, federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to FDA so it is likely that adverse events from compounded versions of these drugs are underreported.
The agency investigates reports of suspected counterfeit drugs to determine the public health risks and the appropriate regulatory response. FDA monitors the internet for fraudulent or unapproved drugs and has issued warning letters to stop the distribution of illegally marketed semaglutide and tirzepatide. These illegally marketed drugs may be counterfeit, could contain the wrong ingredients or harmful ingredients, or could contain too little, too much or no active ingredient at all.
FDA has warned companies that have illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that are falsely labeled “for research purposes” or “not for human consumption.” These products have been sold directly to consumers for human use with dosing instructions. The agency urges consumers not to purchase these products which are of unknown quality and may be harmful to their health.
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