If you have been on GLP-1 or are considering a treatment, one of the question that immediately comes to mind is: which one is better , semaglutide or tirzepatide? And while there are so much marketing pushing for one over the other, it is nearly impossible to understand the why. In this article, we will attempt to address some of your concerns from a research-based angle.
Tirzepatide vs Semaglutide: Is One Better Than The Other?
Tirzepatide and semaglutide both show significant efficacy in reducing HbA1c and body weight, with tirzepatide demonstrating slightly better outcomes at its highest doses. However, it's important to note that tirzepatide's 15mg dose is nearly 5-10 times higher than semaglutide's 2mg dose.
The enhanced efficacy of tirzepatide may be attributed to its dual action as both a GLP-1 and GIP receptor agonist, compared to semaglutide's single GLP-1 receptor agonist mechanism. Additionally, the higher absolute dose of tirzepatide might allow for greater receptor activation, although this doesn't necessarily translate to better tolerability.
Efficacy: Tirzepatide 5 mg vs Semaglutide 1 mg
| Measure | Tirzepatide 5 mg | Semaglutide 1 mg |
|---|---|---|
| HbA1c Reduction | -2.01% | -1.86% |
| Weight Loss | -7.6 kg | -6.2 kg |
| Patients achieving HbA1c <7% | 82% | 79% |
Efficacy: Tirzepatide 10 mg vs Semaglutide 2 mg
| Measure | Tirzepatide 10 mg | Semaglutide 2 mg |
|---|---|---|
| HbA1c Reduction | -2.24% | -2.2% |
| Weight Loss | -9.3 kg | -6.9 kg |
| Patients achieving HbA1c <7% | 86% | 84% |
Sources: Tirzepatide data: Frías JP, et al. N Engl J Med. 2021;385(6):503-515.
Cost Comparison Between Compounded Semaglutide and Tirzepatide
We sampled the 9 most popular weight loss programs including Zeuss Health, Allan Meds, Eden Health, TeleFitMD, Costco/Sesame, Fella Health, Ro Body Program, Emerge Health, Henry Meds, Ivím Health and calculate the average cost for each medication.
Right off the bat, you can see that though Tirzepatide is a more trendy medication, it also costs nearly 50% more.
| Medication Type | Average Monthly Cost | Total Cost for 6 Months | Percentage Difference |
|---|---|---|---|
| Compounded Semaglutide | $297.22 | $2,417.99 | - |
| Compounded Tirzepatide | $448.11 | $3,196.21 | 50.77% |
Is Tirzepatide Worth it?
The short answer is: it depends. For those who are starting on GLP-1, the high cost of Tirzepatide might not be as sustainable compared to Semaglutide. However, at higher doses, the dual action nature of Tirzepatide might justify the cost as it leads to better outcomes for patients within the clinical trials.
We found up to nearly half of individuals on Tirzepatide have thought about switching to a lower-cost alternative when titrating up to a higher dose.
Equivalent Doses for popular GLP-1 Agents
GLP-1RA Conversion Guide (Based on Beth Israel Lahey Health, 11/2022)
Before deciding to switch, you must consult with the prescribing provider due to several factor: (1) most patients are on multiple medications, therefore, it is important to get expert opinion how how you should plan the transition to make sure there is no drug interaction and (2) your insurance might not approve the change or the cost can be huge.
| Drug (Brand Name) | Frequency | Dose 1 | Dose 2 | Dose 3 | Dose 4 |
|---|---|---|---|---|---|
| Dulaglutide (Trulicity)* | Weekly | 0.75 mg | 1.5 mg | 3 mg** | 4.5 mg** |
| Semaglutide (Ozempic)* | Weekly | 0.25 mg† | 0.5 mg | 1 mg | 2 mg |
| Liraglutide (Victoza)* | Daily | 0.6 mg† | 1.2 mg | 1.8 mg | - |
| Oral Semaglutide (Rybelsus) | Daily | 3 mg† | 7 mg | 14 mg | - |
| Exenatide (Bydureon BCise)‡ | Weekly | 2 mg | - | - | - |
| Exenatide (Byetta)§ | Twice Daily | 5 mcg | 10 mcg | - | - |
| Tirzepatide (Mounjaro)¶ | Weekly | 2.5 mg† | 5 mg | 7.5 mg | 10 mg |
Agents with ASCVD evidence † Starting doses not considered therapeutic. Increase dose after indicated duration, if tolerating. ‡ Increased risk of injection site reactions vs. Trulicity, Ozempic, and Victoza. § Rarely used, not recommended to initiate ¶ Given novel mechanism (GIP/GLP1), consider starting at initiation dose of 2.5 mg once weekly x 4 weeks, then increase to 5 mg once weekly. Continue to increase by 2.5 mg increments every 4 weeks as tolerated for additional glycemic control. Not currently indicated for ASCVD risk reduction. ** Additional A1c reduction not as significant as weight reduction at higher doses
Which Medication Has Worse Side Effects?
In terms of side effects and discontinuation rate (people who drop out because they couldn't handle it anymore), Tirzepatide was reported to have more people experiencing side effects and nearly 2X drop out rate compared to Semaglutide.
A recent study found that only less than half of GLP-1 patients stick to the treatment after 6 months and less than one third after a year. Semaglutide actually performed the best with 1-year adherence rate at 47.1%.
Gastrointestinal Side Effects (SURPASS-2 Trial Data)
The side effect profile of GLP-1 receptor agonists, including both Tirzepatide and Semaglutide, is primarily characterized by gastrointestinal events. The SURPASS-2 trial provides detailed comparative data on these side effects for Tirzepatide at a 15mg dose and Semaglutide at a 1mg dose.
| Side Effect | Tirzepatide 15mg | Semaglutide 1mg |
|---|---|---|
| Nausea | 22% | 18% |
| Diarrhea | 14% | 12% |
| Vomiting | 10% | 8% |
Nausea: The incidence of nausea was higher in the Tirzepatide 15mg group (22%) compared to the Semaglutide 1mg group (18%). Nausea is a common issue with GLP-1 therapies, as these medications slow gastric emptying, contributing to the sensation of nausea.
Diarrhea: Diarrhea was reported by 14% of patients taking Tirzepatide 15mg, compared to 12% of those on Semaglutide 1mg. The occurrence of diarrhea can be attributed to the effects of GLP-1 agonists on the gastrointestinal tract, influencing bowel movements and leading to increased frequency or looseness of stools.
Vomiting: Vomiting was noted in 10% of patients receiving Tirzepatide 15mg, whereas it was observed in 8% of patients on Semaglutide 1mg. Vomiting, similar to nausea, is a result of delayed gastric emptying and the central effects of these medications on the vomiting center in the brain.
Discontinuation Rates Due to Adverse Events
Adverse events can significantly impact the continuation of treatment. The SURPASS-2 trial highlighted that discontinuation rates due to adverse events were notably higher for Tirzepatide at a 15mg dose compared to Semaglutide at a 1mg dose.
| Medication | Discontinuation Rate |
|---|---|
| Tirzepatide 15mg | 9% |
| Semaglutide 1mg | 4% |
Tirzepatide 15mg: The trial showed that 9% of patients on Tirzepatide discontinued the medication due to adverse events. This higher discontinuation rate reflects the increased incidence and severity of side effects, which can be a deterrent for ongoing treatment adherence.
Semaglutide 1mg: In contrast, the discontinuation rate for patients on Semaglutide was lower, at 4%. This suggests that while Semaglutide also causes gastrointestinal side effects, they may be more tolerable or less frequent, leading to better overall adherence.
Frequently Asked Questions
Are there any major differences in the mechanisms of action between Tirzepatide and Semaglutide?
Yes, Tirzepatide acts on both GLP-1 and GIP receptors, while Semaglutide targets only GLP-1 receptors. This dual action of Tirzepatide may contribute to its slightly higher efficacy in some patients.
What are the primary benefits of using Tirzepatide over Semaglutide?
Tirzepatide has shown slightly better results in reducing HbA1c levels and promoting weight loss compared to Semaglutide, especially at higher doses. However, individual responses may vary.
What are the common side effects associated with Tirzepatide and Semaglutide?
Both medications primarily cause gastrointestinal side effects, such as nausea, diarrhea, and vomiting. These side effects tend to be more pronounced with higher doses of Tirzepatide.
How do the discontinuation rates due to adverse events compare between Tirzepatide and Semaglutide?
Tirzepatide has a higher discontinuation rate (9%) compared to Semaglutide (4%), mainly due to the severity of gastrointestinal side effects.
Is there a significant cost difference between Tirzepatide and Semaglutide?
Yes, compounded Tirzepatide is generally about 50% more expensive than compounded Semaglutide, making cost a significant consideration for many patients.
Can I switch between Tirzepatide and Semaglutide easily?
Switching between these medications should be done under medical supervision due to potential differences in dosage, side effects, and drug interactions. Consulting with a healthcare provider is essential for a safe transition.
How long do patients typically adhere to GLP-1 therapies like Tirzepatide and Semaglutide?
Adherence rates vary, but Semaglutide has shown better one-year adherence at 47.1% compared to other GLP-1 therapies. Many patients may stop treatment due to side effects or cost.
What are the equivalent doses of Tirzepatide and Semaglutide?
The dosing regimens for these medications differ significantly, with Tirzepatide available in higher doses. For example, Tirzepatide's doses range from 2.5 mg to 15 mg weekly, while Semaglutide's doses range from 0.25 mg to 2 mg weekly.
Is it safe to use Tirzepatide or Semaglutide with other medications?
Both medications can interact with other drugs. It's crucial to discuss all medications you're taking with your healthcare provider to avoid adverse interactions and to adjust dosages appropriately.