With increasing media attention on weight loss and diabetes medications like semaglutide and tirzepatide, many individuals seek to understand the differences between these two medications. Both have gained popularity due to their effectiveness, but it’s important to understand their differences and similarities to better prepare you for conversations with a licensed medical provider about whether these medications are right for you. This article aims to provide a detailed comparison of tirzepatide and semaglutide, two highly effective medications for obesity management and type 2 diabetes treatment.
Understanding Semaglutide and Tirzepatide
Semaglutide and tirzepatide are both GLP-1 agonist prescription medicines used with diet and exercise to treat people with type 2 diabetes or to help people lose weight and maintain that weight loss. These medicines are available in various brand names, such as Ozempic, Rybelsus, or Wegovy (contains semaglutide) and Mounjaro or Zepbound (contains tirzepatide).
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, mimicking the natural GLP-1 hormone in our bodies. It belongs to the drug class of GLP-1 receptor agonists, which stands for glucagon-like peptide-1. It mimics a hormone your gut already produces, which helps regulate appetite and blood sugar levels. Tirzepatide, on the other hand, is a dual-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist and binds to both GIP and GLP-1 receptors. Tirzepatide is a dual agonist acting on 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.
Indications and Uses
Both medications are used for weight management. Ozempic is also approved to reduce the risk of a major cardiovascular event (like a heart attack or stroke) in adults with type 2 diabetes. In Jan 2025, Ozempic was also approved to reduce the risk of worsening kidney disease and cardiovascular death in patients with type 2 diabetes and chronic kidney disease. These drugs can help you reach your A1C goal, which can prevent diabetes complications like heart and blood vessel disease, nerve or vision damage, and kidney failure. Wegovy was Granted Accelerated Approval in the US for the Treatment of MASH on August 15, 2025.
Efficacy in Weight Loss
Both medications are effective for weight loss and diabetes management, each with its own benefits and potential drawbacks. While both medications are used for weight management, Tirzepatide has shown slightly higher effectiveness. 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.
Read also: Comprehensive guide: Tirzepatide and Semaglutide for weight management
In a phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks. The primary end point was the percent change in weight from baseline to week 72. The least-squares mean percent change in weight at week 72 was −20.2% with tirzepatide and −13.7% with semaglutide (P<0.001). Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
Impact on Waist Circumference
In addition to overall weight loss, both medications also impact waist circumference. The trial also assessed the change in waist circumference from baseline to week 72. The least-squares mean change in waist circumference was −18.4 cm with tirzepatide and −13.0 cm with semaglutide (P<0.001).
Dosing and Administration
Mounjaro and Ozempic are given as a weekly subcutaneous (under the skin) injections in the abdomen, thigh, or upper arm. You, or a caregiver, can learn to give these injections at home. Mounjaro, Wegovy, Ozempic and Zepbound are given once per week as injections under the skin (subcutaneously) in the stomach area (abdomen), thigh or upper arm. Swallow the Rybelsus tablet whole (do not crush, split or or chew it).
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.
With any of these medicines, your doctor will start you with lower doses to help prevent common stomach side effects like nausea, vomiting, diarrhea which are common to drugs in the incretin mimetic class. 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.
Read also: Transformations with Ozempic
Cardiovascular Benefits
Semaglutide (brands Ozempic and Wegovy) has been shown to reduce cardiovascular risks, like heart attack, stroke and heart-related death, in patients with type 2 diabetes or obesity and established heart disease. Both products are FDA-approved for this use. Semaglutide (Ozempic and Wegovy) have been shown to reduce cardiovascular risks like heart attack, stroke and heart-related death in patients with established heart disease. Semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are both in the class of drugs known as incretin mimetics and are similar but have some differences in how they work and dosing.
Side Effects and Tolerability
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.
Side effects are similar between tirzepatide and semaglutide, probably because they work in a similar manner for similar indications. Stomach side effects can be severe in some patients, but are usually transient and decrease over the first few months of treatment. Most reports of nausea, vomiting, and diarrhea occur when doses are being increased at the start of treatment.
Here's a comparison of the frequency of some common side effects:
Tirzepatide:
- Nausea: 25% to 28%
- Diarrhea: 19 to 23%
- Belching / burping: 4% to 5%
- Vomiting: 8% to 13%
- Constipation: 11% to 17%
- Stomach area pain: 9% to 10%
- Gastroesophageal reflux disease: 4% to 5%
- Heartburn: 9% to 10%
Semaglutide:
- Nausea: 16% to 20%
- Diarrhea: 9%
- Vomiting: 5% to 9%
- Constipation: 3% to 5%
- Heartburn (dyspepsia): 3% to 4%
- Stomach (abdominal) pain: 6% to 7%
How often side effects occur with tirzepatide and semaglutide cannot be compared outside of clinical studies as patient types, doses and study designs may differ between the studies.
Read also: Semaglutide Without Diet Changes
Both tirzepatide and semaglutide can slow gastric emptying (which is slowed or stopped movement of food through your digestive tract). In 2023, the FDA updated the side effects for Ozempic (semaglutide) to emphasize that an ileus, an intestinal blockage, has been reported as a possible side effect. The FDA cannot reliably determine how often this side effect occurs or if the drug actually caused the ileus due to the voluntary nature of the reports.
Contraindications and Warnings
Individuals with a history of medullary thyroid cancer or certain other conditions should avoid these medications due to potential risks.
It is important to note that this is not all of the reported side effects, precautions or warnings for semaglutide or tirzepatide and rates will differ among products. Speak to your healthcare provider if you have questions about drug side effects. if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Switching Between Medications
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.
Drug Interactions
Semaglutide and tirzepatide may decrease the absorption of other oral medicines due to the delayed gastric-emptying effect.
Cost and Availability
For many patients, access to these medications is difficult due to high costs and lack of insurance coverage. In some cases, the manufacturer may offer a copay coupon that can help lower your costs if you have commercial insurance.
Semaglutide (Wegovy) injection for weight loss treatment costs about $1418 per month if you are paying cash without insurance or manufacturer's copay cards. Semaglutide for treatment of type 2 diabetes costs $1051 per month for either the Ozempic pen injection or 30 oral tablets of Rybelsus.
Price and insurance coverage are important considerations. Many insurance companies will not cover the costs of these medications, especially for weight loss. Check with your insurance before you decide on a treatment with your doctor.
Meta-Analysis Findings
A meta-analysis is a type of statistical study used to combine the results of multiple clinical trials to answer a related research question.
The meta-analysis contained 22 randomized controlled studies with over 18,000 participants. Researchers found that, compared to a placebo, the highest dose of tirzepatide (15 mg given once weekly) was most effective at reducing HbA1c (mean difference of 2%). Tirzepatide doses of 10 mg or 15 mg were more effective than 1 mg or 2 mg doses of semaglutide at lowering body weight.
Cost-Effectiveness Analysis
A 2023 study determined the cost needed to treat (CNT) to achieve a 1% reduction in body weight using tirzepatide 15 mg vs. semaglutide 2.4 mg.
Head-to-Head Study: SURPASS-2
In the Phase 3, head-to-head study SURPASS-2, tirzepatide (Mounjaro) was compared to semaglutide (Ozempic) in an open-label, 40-week long study with over 1,870 participants with type 2 diabetes. Mounjaro 5 mg, 10 mg, and 15 mg injections were compared to semaglutide (Ozempic) 1 mg injections in adults with type 2 diabetes whose blood sugars were not controlled with 1,500 mg/day of metformin alone.
MASH Treatment
Wegovy Granted Accelerated Approval in the US for the Treatment of MASH. August 15, 2025. MASH is a progressive ongoing liver disease leading to inflammation and damage caused by a buildup of fat in the liver. It can progress to liver cancer and become fatal if not properly managed.
Considerations for Treatment Selection
You and your healthcare provider should consider your individual needs when selecting a treatment for type 2 diabetes or weight loss. What may be the best treatment for others may not be the best for you.
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