Tirzepatide vs. semaglutide: how they differ
Both are weekly injections that quiet appetite. One acts on a single hormone receptor and the other on two, and that difference shows up in the research.
At a glance
Semaglutide acts on one gut-hormone receptor, GLP-1. Tirzepatide acts on two, GLP-1 and GIP. In their FDA-approved weight-management forms (Wegovy and Zepbound) both are once-weekly injections that start low and increase over weeks, and both most often cause stomach and bowel side effects. In a 72-week head-to-head trial, people taking tirzepatide lost more weight on average than people taking semaglutide.1 A licensed clinician decides which, if either, is appropriate for you.
In this guide8 sections
One receptor or two
Semaglutide copies GLP-1, a hormone the gut releases after eating that slows stomach emptying, increases fullness, and helps regulate blood sugar. Tirzepatide activates the GLP-1 receptor and the receptor for GIP, a second gut hormone, which is why it is sometimes called a dual agonist.
FDA approved tirzepatide as Zepbound for chronic weight management in 2023; the same medicine was already approved as Mounjaro for type 2 diabetes.2 Semaglutide is approved as Wegovy for weight management and as Ozempic for type 2 diabetes.3
Side by side
The table compares the FDA-approved weekly injections. Compounded versions are prepared by licensed U.S. pharmacies and are not FDA-approved4, so the trial results below describe the brand products, not any compounded product.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Acts on | GLP-1 receptor | GLP-1 and GIP receptors |
| FDA-approved for weight | Wegovy | Zepbound |
| How often | Once a week, under the skin | Also once a week, under the skin |
| Starting the dose | Starts low and increases in steps over several months | Starts low and increases over 4 to 20 weeks |
| Most common side effects | Nausea, diarrhea, vomiting, constipation | Similar: nausea, diarrhea, vomiting, constipation |
Dosing cadence
Both medicines are injected once a week on the same day, with or without food. Each starts at a low dose that is raised every few weeks so the gut can adjust; FDA describes Zepbound’s increases as happening over four to 20 weeks toward a target of 5, 10, or 15 mg once weekly.2
Oral forms exist too. Daily oral semaglutide tablets are FDA-approved, and some pharmacies compound oral versions of both medicines. Compounded oral forms have far less published evidence than the weekly injections, which is worth weighing if you prefer to avoid needles.
Side effects in plain terms
The most common effects of both are nausea, diarrhea, vomiting, constipation, and stomach discomfort. In the head-to-head trial, most of these were mild to moderate and occurred primarily during dose escalation1, which is why the dose is raised slowly.
Both carry a boxed warning because they caused thyroid tumors in rats; it is not known whether they do so in people.35 A clinician will ask whether you or anyone in your family has had medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN 2). Severe stomach pain, repeated vomiting, or signs of dehydration need prompt medical advice. Our GLP-1 side effects guide covers what to track.
What the head-to-head trial found
SURMOUNT-5 randomly assigned 751 adults with obesity, but without type 2 diabetes, to the highest dose they could tolerate of tirzepatide or semaglutide for 72 weeks. Average weight change was 20.2% with tirzepatide and 13.7% with semaglutide.1
These are averages. Some people lose more, some lose less, and some stop because of side effects. The trial was open-label, meaning participants knew which drug they took, and it was funded by the maker of tirzepatide.1
Who might consider which
There is no single right answer, and a licensed clinician decides whether either medicine is appropriate. The decision usually weighs your goals, past response to either drug, how you tolerate side effects, other conditions and medicines, insurance coverage, and cost.
FDA-approved Wegovy and Zepbound remain options, especially if your insurance covers them.
FDA has not reviewed compounded semaglutide or tirzepatide for safety or effectiveness.4 Trial results for FDA-approved products do not apply to compounded versions. See how the Everdawn weight-loss program works.
- Your goal and how much support you want
- Any prior GLP-1 use and how it went
- Type 2 diabetes, kidney disease, gallbladder or pancreas history
- Thyroid cancer or MEN 2 in you or your family
- Pregnancy or plans for pregnancy
- Coverage and the full monthly price
Common questions
Is tirzepatide stronger than semaglutide?
In the SURMOUNT-5 trial, average weight loss at 72 weeks was greater with tirzepatide than with semaglutide. That does not mean it is the right choice for everyone; tolerance, health history, and cost also matter.
Can I switch from semaglutide to tirzepatide?
Switching is possible, but the starting dose and timing should be set by a clinician. Do not convert doses yourself; the medicines are not interchangeable milligram for milligram.
Are compounded versions the same as Wegovy or Zepbound?
No. Compounded semaglutide and tirzepatide are prepared by licensed pharmacies and are not FDA-approved. The trial results describe the FDA-approved products.
Which has fewer side effects?
Both most often cause nausea, diarrhea, vomiting, and constipation, mostly while the dose is rising. Individual tolerance varies, and a slow dose increase usually helps.
References
- Source 1: Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med, 2025 (opens in a new tab)
- Source 2: FDA: FDA approves new medication for chronic weight management (Zepbound) (opens in a new tab)
- Source 3: MedlinePlus (NIH): Semaglutide injection (opens in a new tab)
- Source 4: FDA: Concerns with unapproved GLP-1 drugs used for weight loss (opens in a new tab)
- Source 5: MedlinePlus (NIH): Tirzepatide injection (opens in a new tab)
A number in the text links to the source for that statement.
This guide provides general educational information and is not medical advice, diagnosis, or treatment. Treatment decisions require an appropriately licensed clinician who understands your history and circumstances.
Images are illustrations, not Everdawn members or clinicians.