Semaglutide vs Tirzepatide: Which GLP-1 Is Right for You?

the short answer

Tirzepatide produced more weight loss in the head-to-head trial, about 20 percent versus 14 percent at 72 weeks. Semaglutide has the longer track record, the heart-outcomes data, and the lower price, and it is enough for many people. A physician picks based on goal, history, tolerance, and budget.

Both are prescription medications, and Pepvio prescribes both: compounded semaglutide, the same molecule as Ozempic® and Wegovy®, and compounded tirzepatide, the same molecule as Mounjaro® and Zepbound®. You do not have to choose before your visit. The physician who reviews your intake recommends one, and you can ask for the other if you have a reason.

This article covers what the two have in common, where they differ, what the trials measured, and the situations where each one tends to be the better fit.

what they have in common

Semaglutide and tirzepatide are both modified copies of GLP-1, a hormone your gut releases after a meal. GLP-1 tells the brain you have eaten, slows how fast the stomach empties, and prompts the pancreas to release insulin when blood sugar is high. The natural hormone lasts a few minutes. Both medications are altered to last about a week, which is why each is a once-weekly injection under the skin.

Both start at a low dose and step up every few weeks. The steps give the digestive system time to adjust, and most of the side effects happen during those step-ups rather than at the settled dose. Semaglutide tops out at 2.4 mg a week for weight; tirzepatide tops out at 15 mg. The numbers are not comparable across the two, since they are different molecules with different potencies per milligram.

Both work on appetite. Hunger is lower, fullness arrives sooner, and the amount you eat drops without a conscious effort to restrict. Neither one raises the rate at which you burn calories. What is a GLP-1 covers the hormone and the medication class in more detail.

how they differ

Semaglutide copies one hormone. Tirzepatide copies two: GLP-1 and a second gut hormone called GIP, which is released after meals and appears to add to the effect on appetite and on how the body handles blood sugar. That second signal is the most likely reason the tirzepatide trials show a larger average loss.

The two also differ in how long they have been in use. Semaglutide was approved for type 2 diabetes in December 2017 and for weight in June 2021. Tirzepatide was approved for diabetes in 2022 and for weight in late 2023. Semaglutide has roughly four more years of prescribing history, and, as covered below, a completed trial on heart attacks and strokes that tirzepatide does not yet have in people without diabetes.

The third difference is cost. Tirzepatide costs the pharmacy more, and the compounded version is priced higher than compounded semaglutide at Pepvio and everywhere else. The GLP-1 page has current pricing for both, and the GLP-1 cost calculator shows what each plan comes to over a year.

the weight-loss data

Three trials matter here. Each one enrolled adults with obesity, or overweight with a weight-related condition, who did not have diabetes.

STEP 1 (semaglutide). In 1,961 adults, semaglutide 2.4 mg produced an average loss of 14.9 percent of body weight over 68 weeks, against 2.4 percent on placebo. Half of the participants on semaglutide lost 15 percent or more.^[1]

SURMOUNT-1 (tirzepatide). In 2,539 adults, tirzepatide produced an average loss of 15.0 percent at the 5 mg dose, 19.5 percent at 10 mg, and 20.9 percent at 15 mg over 72 weeks, against 3.1 percent on placebo. At the 15 mg dose, 57 percent of participants lost 20 percent or more.^[2]

SURMOUNT-5 (head to head). In 2025, a trial of 751 adults compared the two directly at each person's highest tolerated dose for 72 weeks. Tirzepatide produced an average loss of 20.2 percent; semaglutide produced 13.7 percent. Tirzepatide also took more inches off the waist, about 7 inches versus 5, and more participants on it reached every threshold measured, from 10 percent down to 25 percent.^[3]

The trial results are averages, and individual results vary. Some people on semaglutide lose 20 percent; some people on tirzepatide lose 10. The averages tell you which molecule is more likely to get you further, and that is what the physician weighs against your goal.

side effects compared

The side-effect profiles are close to identical in kind. Nausea, diarrhea, constipation, and reduced appetite are the most common with both, they show up mostly during dose step-ups, and they are mild to moderate for most people and fade as the dose settles.

The difference is in degree. In STEP 1, 4.5 percent of people on semaglutide stopped because of digestive side effects, against 0.8 percent on placebo.^[1] In SURMOUNT-1, side effects of any kind led 4.3 to 7.1 percent of people on tirzepatide to stop, depending on dose, against 2.6 percent on placebo.^[2] In the head-to-head trial, digestive side effects led 5.6 percent of the semaglutide group to stop and 2.7 percent of the tirzepatide group.^[3] That trial was open-label, meaning participants knew which drug they were on, which can affect how side effects get reported. Taken together, the two are in the same range, and tirzepatide was not the harder one to tolerate.

Both carry the same class warnings: they are not used in pregnancy or in anyone with a personal or family history of medullary thyroid cancer, and a history of pancreatitis needs a physician's review before either is prescribed. Those are among the questions on the intake, and they apply to both medications rather than steering you toward one.

the case for semaglutide

Semaglutide has been prescribed since 2017, about four years longer than tirzepatide, and it has the longer safety record of the two.

It is also the one with completed heart-outcomes data in people without diabetes. In the SELECT trial, 17,604 adults aged 45 and older with existing heart disease and a BMI of 27 or higher took semaglutide 2.4 mg or placebo for about three years. Heart attack, stroke, or death from cardiovascular causes occurred in 6.5 percent of the semaglutide group and 8.0 percent of the placebo group, a 20 percent lower relative risk.^[4] The equivalent tirzepatide trial in people without diabetes is still underway. If you have heart disease or several risk factors for it, this is the finding your physician will weigh most.

It costs less, and the gap adds up over a year. And for many people, a 15 percent average loss covers the goal. Someone who weighs 200 pounds and wants to lose 25 to 30 is inside semaglutide's range. Starting with the lower-cost option and reassessing after a few months is a reasonable plan, since switching is straightforward.

the case for tirzepatide

Tirzepatide's case is the larger average loss. The separate trials and the head-to-head trial both put it ahead of semaglutide by about six percentage points, and the head-to-head trial found that more people on it reached each milestone. The tirzepatide guide covers the molecule and the trial history in more depth.

It tends to be the recommendation when the goal is larger. Someone with 60 or more pounds to lose is more likely to get there on tirzepatide, and more likely to get there within the first year. It is also the usual next step for someone who lost weight on semaglutide and stalled short of their goal: the second hormone signal often restarts progress.

It costs more. Whether the added loss is worth the added cost is a personal calculation, and the cost calculator is built for exactly that comparison.

switching between them

A physician can move you from one to the other, in either direction. The common reasons: a plateau on semaglutide, side effects that do not settle on one of them, a change in budget, or a goal that turns out to be larger or smaller than expected.

The new medication usually starts at a low dose and steps up on its own schedule, rather than picking up at the dose you were on. The two molecules are not interchangeable by milligram, and starting low on the new one is how the digestive side effects are kept in check during the change. Most people notice the switch as a few weeks of readjustment, similar to the first weeks on the original medication. Your physician sets the timing so there is no gap and no overlap between the two.

how Pepvio decides

The process starts with an online visit that takes about 2 minutes: your weight history, your goal, your health conditions and medications, and any prior experience with either medication. A licensed U.S. physician reviews it and recommends semaglutide or tirzepatide based on the factors above. If you have a preference, say so in the intake, and the physician will tell you if there is a reason to go the other way.

You are charged only after the physician approves. Both medications come with Price Lock: the monthly price is set at the start, it does not go up as your dose steps up, and it does not go up in the second year. Every dose increase is included. A licensed U.S. compounding pharmacy fills the prescription and ships it to you.

If you already have a sense of which one fits, the visit below is the next step. If you do not, that is fine too; the physician makes the call, and you can change it later.

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