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Tirzepatide vs Semaglutide

Sep 14, 2023
Tirzepatide vs Semaglutide

Glucagon-like peptide 1 (GLP-1) agonists, such as Ozempic (semaglutide), Wegovy (semaglutide), and Mounjaro (tirzepatide), are used to treat obesity because they have been shown to work in clinical trials.

Since all three medications have similar uses, it is important to compare tirzepatide vs semaglutide in terms of mechanism of action, dosing, side effects, and clinical trial data. Understanding the similarities and differences among these medications can help you work with your doctor to develop a weight-management treatment plan.

Indications for Tirzepatide vs Semaglutide

Ozempic and Wegovy are brand names for semaglutide. They are both manufactured by Novo Nordisk. Ozempic is used to treat type 2 diabetes and prevent cardiovascular disease. Wegovy is used for chronic weight management in adults and adolescents aged 12 and older. Both medications are injectables and are intended to be used as part of a comprehensive plan that includes a well-balanced, reduced-calorie diet and exercise.

Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist manufactured by Eli Lilly. It is also an injectable and is approved to treat type 2 diabetes. Like Ozempic and Wegovy, people taking Mounjaro experience significant weight loss.

After submitting clinical trial results that support its weight-loss potential, safety, and efficacy, the FDA gave Mounjaro a second indication: to treat obesity.

Medication indications are based on the outcomes of clinical trials. For example, to receive an indication for obesity treatment, a manufacturer must demonstrate that their drug safely and effectively treats obesity. Off-label use is when a clinician makes a medical judgment that a medication is an appropriate choice to treat a patient for a medical condition.

weight loss treatment

Eligibility: Tirzepatide vs Semaglutide

Semaglutide is indicated for weight management, so eligibility criteria focus on body mass index, or BMI. People with a BMI of 30 or greater are eligible to take semaglutide. People with a BMI of 27 or higher and a weight-related medical condition such as high blood pressure, high cholesterol, or type 2 diabetes may also qualify. Adolescents must have a BMI at or above the 95th percentile for their age and weight.

The eligibility guidelines to use tirzepatide as an obesity treatment are the same as for semaglutide.

Mechanism of Action: Tirzepatide vs Semaglutide

Tirzepatide and semaglutide are GLP-1 receptor agonists. GLP-1 agonists mimic the action of GLP-1 in the body. They boost insulin production in the pancreas and, therefore, help control blood sugar levels. They also reduce glucose production in the liver by lowering glucagon release.

GLP-1 agonists slow stomach emptying and reduce intestinal motility, which helps you feel full longer. Slowing stomach emptying helps stabilize blood glucose.

GLP-1 agonists also act in the brain. The gut releases GLP-1 after you consume food. It tells the brain you are full. Specialized neurons in the brain regulate food intake and energy expenditure. Other neurons that control reward, emotion, memory, attention, and cognition modulate weight-control neuronal activity. GLP-1 agonists reduce hunger and are thought to reduce food cravings.

Tirzepatide is also a GIP agonist. It boosts insulin production and sensitivity. It slows stomach emptying by reducing stomach acid production.

A scale and weights

Dosing: Tirzepatide vs Semaglutide

Tirzepatide and semaglutide are injectables that use a gradually increasing dose to minimize side effects.

Wegovy (semaglutide) comes in pre-filled, single-dose pens that deliver doses of 0.25, 0.5, 1.0, 1.7, or 2.4 mg. The dose is slowly increased after four weeks on each dose until a 2.4 mg weekly dose is reached.

Ozempic (semaglutide) comes in a 2 mg/1.5 ml and 2 mg/3 ml pen that is used to deliver doses of 0.25 mg or 0.5mg. A 4 mg/3 ml pen delivers 1 mg of Ozempic per dose, and an 8 mg/3 ml pen delivers 2 mg per dose. The dose of Ozempic is slowly increased to a maximum of 2mg weekly. The starting dose of 0.25 mg is ineffective for blood glucose control, per the manufacturer.

Mounjaro (tirzepatide) is available in multiple doses, from 2.5 mg to 15 mg. The starting dose is 2.5 mg, injected under the skin once a week. Every four weeks, the dose can be increased in 2.5 mg increments. The maximum dose is 15 mg, injected subcutaneously once a week.

Wegovy side effects

Side Effects: Tirzepatide vs Semaglutide

The GLP-1 medications cause similar gastrointestinal side effects. Side effects typically increase when the drug is first started and when the dosage is increased.

Side effects associated with semaglutide include:

  • Nausea (44%)
  • Diarrhea (30%)
  • Vomiting (24%)
  • Constipation (24%)
  • Stomach pain (20%)
  • Headache (14%)
  • Fatigue (11%)
  • Heartburn (9%)
  • Dizziness (8%)
  • Stomach bloating (7%)
  • Burping/flatulence (7%)
  • Low blood sugar in people with type 2 diabetes (6%)
  • Gas (6%)
  • Gastroenteritis (6%)
  • Acid reflux (5%)
  • Stomach irritation (4%)
  • Viral gastroenteritis (4%)
  • Hair loss (3%)


Rare but more serious side effects include inflammation of the pancreas, gallbladder disease, diabetic retinopathy complications, and kidney disease. In animal studies, semaglutide increased the risk of thyroid cancer. If you have a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome type 2, you should not take semaglutide.

Tirzepatide side effects include:

  • Nausea
  • Diarrhea
  • Decreased appetite
  • Vomiting
  • Constipation
  • Indigestion
  • Stomach pain

Mounjaro (tirzepatide) can cause the same serious side effects as Wegovy and Ozempic (semaglutide). These include an increased risk of thyroid C-cell tumors, pancreatitis, low blood sugar, allergic reactions, acute kidney injury, severe gastrointestinal disease, complications from diabetic retinopathy, and acute gallbladder disease.

clinical trials evaluate tirzepatide vs semaglutide

Clinical Trial Results: Tirzepatide vs semaglutide

The FDA approved Wegovy to treat obesity based on the results of the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials. The average weight loss was almost 15% for adults and 16% for adolescents.

Ozempic clinical trials (SUSTAIN) included a series of eight trials focused on type 2 diabetes management and cardiovascular outcomes. Clinical trial participants taking Ozempic lowered their hemoglobin A1C (HgA1C) by over 1%, indicating that they achieved significantly better glucose control, as HgA1C is a measurement of average blood glucose over three months. The secondary clinical trial’s endpoint was weight loss. When patients with type 2 diabetes took Ozempic, they averaged 6% to 7% weight loss.

In phase 3 clinical trials, participants with type 2 diabetes treated with Mounjaro lost an average of 12 to 25 pounds over 52 weeks. They had a reduction in HgA1C of between 1.8% and 2.4%.

In the Phase 3 SURMOUNT 1 study, at the end of 72 weeks, the mean weight loss for participants taking Mounjaro was:

  • 15% for the 5 mg dose
  • 19.5% for the 10 mg dose
  • 20.9% for the 15 mg dose
  • 3.1% for placebo

If you meet the eligibility guidelines and are interested in taking a GLP-1 agonist such as tizepatide or semaglutide to support your weight loss efforts, contact an Invigor Medical treatment specialist to learn more about these medications.

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Tirzepatide vs Semaglutide
Disclaimer
While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.

Tirzepatide vs Semaglutide

Leann Poston, M.D.

Dr. Leann Poston is a licensed physician in the state of Ohio who holds an M.B.A. and an M. Ed. She is a full-time medical communications writer and educator who writes and researches for Invigor Medical. Dr. Poston lives in the Midwest with her family. She enjoys traveling and hiking. She is an avid technology aficionado and loves trying new things.

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