Tirzepatide vs Semaglutide Weight Loss Medication Comparison

Tirzepatide vs Semaglutide

Both tirzepatide and semaglutide are prescription medications used alongside diet and exercise to treat type 2 diabetes and aid in weight loss. These medications are marketed under various brand names: Ozempic, Rybelsus, and Wegovy for semaglutide, and Mounjaro and Zepbound for tirzepatide. Cost-effective compound prescriptions of tirzepatide and semaglutide are available and are often prescribed for people whose insurance does not cover the name brands.

Both name-brand and compound tirzepatide and semaglutide can be prescribed by JoinFridays. Be sure to use code “MADISON.”

Mechanism of Action

  • Semaglutide (Ozempic, Wegovy, Rybelsus): A glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the natural GLP-1 hormone, binding to GLP-1 receptors to exert its effects. Study results indicate an average weight reduction of 12.4% with semaglutide.
  • Tirzepatide (Mounjaro, Zepbound): A dual-acting glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that binds to both GIP and GLP-1 receptors, potentially enhancing its action. Study results indicate an average weight reduction of 17.8% with tirzepatide.

These medications work by:

  • Stimulating insulin release from the pancreas to lower blood sugar.
  • Suppressing glucagon secretion to reduce sugar production by the liver.
  • Slowing gastric emptying, which can increase satiety, reduce appetite, and promote weight loss.

Approved Uses for Mounjaro, Ozempic, and Rybelsus

  • Mounjaro, Ozempic, and Rybelsus: Used with diet and exercise to control blood sugar levels in adults with type 2 diabetes.
  • Ozempic: Also approved to reduce the risk of major cardiovascular events (heart attack or stroke) in adults with type 2 diabetes. Mounjaro is undergoing studies for this indication but is not yet approved.

These drugs help achieve A1C goals, preventing complications such as heart and blood vessel disease, nerve or vision damage, and kidney failure. A1C is a test that measures long-term blood sugar control.

  • Mounjaro and Ozempic: Weekly subcutaneous injections in the abdomen, thigh, or upper arm. These injections can be administered at home.
  • Rybelsus: Oral tablet taken once daily.

Though these medications have shown efficacy in weight loss for type 2 diabetes patients, they are not specifically FDA-approved for weight loss.

Approved Uses for Zepbound and Wegovy

  • Wegovy: Approved for weight loss in adults and children 12 years and older with obesity or excess weight and related health problems (e.g., high blood pressure, high cholesterol). It is also approved to reduce the risk of serious heart issues in adults with heart disease and obesity or overweight.
  • Zepbound: Approved for weight loss in adults with obesity or those who are overweight with related medical problems.

Both medications should be used alongside a reduced-calorie diet and exercise program. They are administered as weekly subcutaneous injections that can be administered at home.

Administration Guidelines

  • Injectable forms (Mounjaro, Wegovy, Ozempic, Zepbound): Given weekly via subcutaneous injections in the abdomen, thigh, or upper arm. Training from a healthcare provider is necessary for home administration.
  • Oral form (Rybelsus): Taken daily on an empty stomach with a sip of water. Must be taken 30 minutes before any other intake.

Compound Medications

Compounded semaglutide and tirzepatide can be prescribed from compound pharmacies and are a fraction of the cost of the name brands. These medications usually come in vials and are self-injected. At JoinFridays GLP-1 Telehealth, semaglutide is $129 a month and tirzepatide starts at $179 a month.

Side Effects

Common side effects for both medications include nausea, vomiting, diarrhea, constipation, indigestion, and abdominal pain. These are often more pronounced when starting the medication or increasing the dose. Serious side effects are rare but may include severe gastrointestinal issues and hypoglycemia when combined with other diabetes treatments.

Comparison Studies and Cost Analysis

  • Efficacy: Studies show tirzepatide may lower A1C levels and lead to more significant weight loss compared to semaglutide, though it may also have higher rates of gastrointestinal side effects.
  • Cardiovascular Benefits: Semaglutide has been shown to reduce cardiovascular risks, whereas studies are still ongoing for tirzepatide.
  • Cost: Tirzepatide (Zepbound) may offer a better value for weight reduction compared to semaglutide (Wegovy), according to some cost analyses.

Choosing Between Tirzepatide and Semaglutide

Factors to consider include:

  • Cardiovascular risk reduction (semaglutide has proven benefits).
  • Side effect profiles (tirzepatide may have milder side effects).
  • Preferred administration method (injection vs. oral tablet).
  • Affordability and insurance coverage.
  • Use in children (Wegovy is approved for those 12 years and older).

Important Safety Information

Both tirzepatide and semaglutide carry boxed warnings about the potential risk of thyroid tumors. They are contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Patients should also be aware of possible pancreatitis, retinopathy, hypoglycemia, and gallbladder disease risks.

Cost Considerations

These medications can be expensive, and insurance coverage may vary. Manufacturer coupons may help reduce costs for eligible patients with commercial insurance.


Choosing between tirzepatide and semaglutide requires careful consideration of individual health needs, potential benefits, side effects, administration preferences, and costs. Discuss with your healthcare provider to determine the most suitable treatment for your condition.