Semaglutide vs Tirzepatide: Weight Loss, Side Effects and Cost Compared
Both are once-weekly shots that curb appetite. Tirzepatide led to more weight loss on average in the first head-to-head trial, while semaglutide usually costs less. Either one can be the right choice.
Semaglutide and tirzepatide are both once-weekly injections for weight loss, but they work a little differently. Semaglutide acts on one gut hormone receptor (GLP-1), while tirzepatide acts on two (GIP and GLP-1). In SURMOUNT-5, the first head-to-head trial, people on tirzepatide lost about 20.2% of their body weight over 72 weeks, compared with about 13.7% on semaglutide. Tirzepatide usually costs more, and the right pick depends on your goals, your budget and how your body handles the medicine.
- Both are weekly shots given under the skin, started low and raised slowly.
- Semaglutide is a GLP-1 receptor agonist. Tirzepatide is a dual GIP and GLP-1 receptor agonist.
- In SURMOUNT-5 (751 adults without diabetes), tirzepatide led to 22.8 kg of average weight loss versus 15.0 kg with semaglutide.
- Side effects are similar for both: mostly nausea, diarrhea, vomiting and constipation, especially while doses go up.
- Both carry an FDA boxed warning about thyroid C-cell tumors seen in rodents.
- Semaglutide is usually the lower-cost option, whether you pay with insurance, a manufacturer program or a cash-pay plan.
Semaglutide vs tirzepatide side by side
This table compares the two molecules using the FDA labels for the weight-loss versions and the main trials behind them. Doses are the label doses for weight management.
| Semaglutide | Tirzepatide | |
|---|---|---|
| How it works | GLP-1 receptor agonist (one hormone pathway) | GIP and GLP-1 receptor agonist (two hormone pathways) |
| How it is taken | Injection under the skin, once a week (an oral tablet version also exists) | Injection under the skin, once a week |
| Starting dose | 0.25 mg weekly for 4 weeks | 2.5 mg weekly for 4 weeks |
| How doses go up | 0.5 mg, 1 mg, 1.7 mg, then 2.4 mg, about every 4 weeks | 5 mg, then up in 2.5 mg steps, at least 4 weeks apart |
| Maintenance and top dose | 1.7 mg or 2.4 mg; may go up to 7.2 mg after at least 4 weeks on 2.4 mg | 5 mg, 10 mg or 15 mg; top dose 15 mg |
| Average weight loss in the main placebo trial | 14.9% at 68 weeks on 2.4 mg (placebo 2.4%), STEP 1 | 20.9% at 72 weeks on 15 mg (placebo 3.1%), SURMOUNT-1 |
| Head-to-head (SURMOUNT-5, 72 weeks) | 13.7% average weight loss | 20.2% average weight loss |
| Most common side effects | Nausea, diarrhea, vomiting, constipation, belly pain, headache, fatigue | Nausea, diarrhea, vomiting, constipation, belly pain, indigestion, injection site reactions, fatigue |
| Boxed warning | Thyroid C-cell tumors in rodents | Thyroid C-cell tumors in rodents |
Sources: the FDA prescribing information on DailyMed for semaglutide 2.4 mg and DailyMed for tirzepatide. For a closer look at each schedule, see our semaglutide dosage chart and tirzepatide dosage guide.
How they work differently
Your gut releases hormones after you eat. Two of them, GLP-1 and GIP, help signal fullness and help your body handle blood sugar.
Semaglutide copies GLP-1. It slows how fast your stomach empties, helps you feel full sooner and lowers food cravings.
Tirzepatide copies GLP-1 too, and it also acts on the GIP receptor. Researchers think this second pathway is part of why tirzepatide led to more weight loss in trials, though exactly how GIP adds to the effect is still being studied.
Both are taken once a week, and both start at a low dose that rises slowly so your body can adjust. If you want the basics on the newer drug first, read what tirzepatide is and how it works.
The head-to-head trial: SURMOUNT-5
Earlier trials tested each drug against a placebo, so their results could not be compared directly. SURMOUNT-5 was the first trial to put the two side by side for weight loss. It was published in the New England Journal of Medicine in 2025.
- Who was in it: 751 adults with obesity, or with overweight plus at least one weight-related health problem, and without type 2 diabetes.
- Doses: each person took the highest dose they could tolerate, either tirzepatide 10 mg or 15 mg, or semaglutide 1.7 mg or 2.4 mg, once a week.
- Length: 72 weeks.
| SURMOUNT-5 result at 72 weeks | Semaglutide | Tirzepatide |
|---|---|---|
| Average change in body weight | -13.7% | -20.2% |
| Average weight lost | 15.0 kg (about 33 lb) | 22.8 kg (about 50 lb) |
| Average change in waist size | -13.0 cm | -18.4 cm |
| Stopped because of stomach side effects | 5.6% | 2.7% |
A few things to keep in mind. The trial was open-label, meaning people knew which drug they were taking, and it was funded by the maker of tirzepatide. These are averages, so some people on semaglutide lost more weight than some people on tirzepatide. Men lost less weight than women on both drugs (American College of Cardiology summary).
💡 What the result does and does not mean
SURMOUNT-5 shows tirzepatide led to more weight loss on average. It does not mean semaglutide fails. A 13.7% average loss is still a large, meaningful change for health.
Side effects and tolerability
The two drugs share most of the same side effects because both act on GLP-1. Most are stomach-related, mild to moderate, and most common while the dose is going up.
On the semaglutide 2.4 mg label, the most common side effects in adults were nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%) and belly pain (20%). The tirzepatide label lists nausea, diarrhea, vomiting, constipation, belly pain, indigestion, injection site reactions, fatigue, allergic reactions, burping, hair loss and acid reflux as its most common side effects.
In SURMOUNT-5, fewer people stopped tirzepatide because of stomach side effects (2.7%) than stopped semaglutide (5.6%). That is one trial, and your own experience may differ.
Serious risks for both include pancreatitis, gallbladder problems, kidney problems from dehydration, low blood sugar when used with some diabetes medicines, and serious allergic reactions. Neither should be used if you or a family member has had medullary thyroid cancer or MEN 2.
- Eat smaller meals and stop when you feel full.
- Go easy on greasy and very sweet foods, which often make nausea worse.
- Drink enough fluids, especially if you have vomiting or diarrhea.
- Tell your prescriber if side effects are hard to manage. Staying at a dose longer is a common fix.
Who might lean which way
There is no single winner for everyone. These are general patterns to bring to your prescriber, not rules.
Which one might fit you better?
Common reasons people and prescribers lean one way:
Semaglutide may fit if
- Cost is a big factor and you want the lower monthly price
- Your goal is a moderate amount of weight loss
- Your insurance covers semaglutide but not tirzepatide
- You want the option of a daily pill instead of a shot
- You have heart disease and your prescriber wants a drug with a heart-risk label
Tirzepatide may fit if
- You have a lot of weight to lose and want the larger average result
- You tried semaglutide and your weight loss stalled
- You had a hard time with semaglutide side effects
- You have obstructive sleep apnea with obesity
- The higher monthly cost fits your budget for the long term
Both drugs work best when you keep taking them. Weight often comes back after stopping, so pick the one you can stay on, both for your body and your wallet.
Switching between them
People switch for many reasons: a weight-loss plateau, side effects, a change in insurance or cost. Switching is common, but it should always go through your prescriber.
- Your prescriber picks the starting dose. There is no official one-to-one dose conversion between semaglutide and tirzepatide on either label. Many people start the new drug near the bottom of its schedule and step up from there.
- Do not take both. Never use the two together or double up while switching.
- Expect some side effects again. Stomach upset can come back for a few weeks on a new drug.
- Timing matters. Your prescriber will tell you when to take the first dose of the new medicine, which is usually when your next weekly dose would have been due.
For more on stepping up a dose, see when to increase your tirzepatide dose.
What each one costs
Price is often what decides it. Below are the brand-name self-pay prices from each manufacturer, then Rx.com's own pricing. Before paying cash, check your insurance first, because coverage is usually the cheapest path.
Brand-name tirzepatide (Zepbound) from Lilly
As of October 2026, Lilly lists these self-pay prices through LillyDirect for Zepbound KwikPen or vials, per one-month supply: $299 for 2.5 mg, $399 for 5 mg, and $449 for 7.5 mg through 15 mg when each refill is completed within 45 days of the last one. Without that timing, the regular price for 10 mg to 15 mg is $699. If your commercial plan covers the Zepbound single-dose pen, the savings card can bring it as low as $25 a month. Check Lilly's Zepbound savings page for current terms.
Brand-name semaglutide (Wegovy) from Novo Nordisk
As of October 2026, NovoCare Pharmacy lists Wegovy pens at $349 a month for 0.25 mg through 2.4 mg and $399 a month for the 7.2 mg dose. New patients can get the first two months of the 0.25 mg and 0.5 mg doses for $199 a month through December 31, 2026. Wegovy tablets start at $149 a month for the lowest dose. With commercial coverage, the savings card can bring the cost as low as $25 a month. See NovoCare's Wegovy price page.
💡 On Medicare?
The Medicare GLP-1 Bridge, which runs July 1, 2026 through December 31, 2027, offers Wegovy and Zepbound KwikPen at a $50 monthly copay for people who meet its BMI rules with prior authorization. If you have Medicare, ask your prescriber about it before paying cash (cms.gov).
| Option (brand, October 2026) | Starting monthly price | Higher doses |
|---|---|---|
| Zepbound via LillyDirect self-pay | $299 (2.5 mg) | $399 to $699 (refill timing affects price) |
| Wegovy pen via NovoCare Pharmacy | $199 for 2 months (new patients), then $349 | $349 up to 2.4 mg; $399 for 7.2 mg |
| Savings card with commercial coverage | As low as $25 | Same |
| Medicare GLP-1 Bridge (if eligible) | $50 copay | $50 copay |
For a dose-by-dose look at the tirzepatide brand, see Zepbound cost by dose.
Compounded semaglutide vs compounded tirzepatide at Rx.com
Through Rx.com, compounded semaglutide starts at $99 a month and compounded tirzepatide starts at $149 a month on a 12-month plan. Each price covers the online provider visit, medication, supplies and cold shipping, with one flat price at every dose and no insurance needed.
Compounded medications are made by a licensed pharmacy for an individual patient. They are not FDA-approved and are not the same as any brand-name medication. FDA removed tirzepatide (December 2024) and semaglutide (February 2025) from its drug shortage list. A state-licensed 503A pharmacy may still compound them for an individual patient when a prescriber documents a clinical need, such as a dose or formulation change. FDA also warns people about unapproved GLP-1 products sold online, so use a licensed pharmacy and a real prescriber. Learn more in our guides to compounded tirzepatide and compounded semaglutide safety.
| Rx.com plan (12-month plan) | From | Included |
|---|---|---|
| Compounded semaglutide | $99/month | Online provider visit, medication, supplies, cold shipping |
| Compounded tirzepatide | $149/month | Online provider visit, medication, supplies, cold shipping |
Getting treatment through Rx.com
If insurance and the manufacturer programs above do not work for you, Rx.com offers compounded semaglutide from $99/month and compounded tirzepatide from $149/month on a 12-month plan. The online provider visit, medication, supplies and cold shipping are included, with one flat price at every dose and no insurance needed. A licensed provider reviews your health history and decides whether either medicine is right for you. Compounded medications are not FDA-approved. Not sure which one to ask about? Start with our short weight-loss quiz.
🚨 When to Contact Your Healthcare Provider
Call your prescriber right away if any of these happen. Call 911 for trouble breathing, fainting or severe pain.
- Severe belly pain that does not go away, with or without vomiting, which can spread to your back: possible pancreatitis.
- Pain in the upper right belly, fever or yellow skin or eyes: possible gallbladder problem.
- Vomiting or diarrhea that keeps you from drinking fluids: risk of dehydration and kidney problems.
- A lump or swelling in your neck, trouble swallowing or a hoarse voice that does not go away.
- Swelling of the face, lips or throat, or a severe rash: possible allergic reaction.
- Shakiness, sweating or confusion if you also take insulin or a sulfonylurea: possible low blood sugar.
Frequently Asked Questions
Is tirzepatide stronger than semaglutide?
On average, tirzepatide led to more weight loss. In SURMOUNT-5, people lost about 20.2% of body weight on tirzepatide versus 13.7% on semaglutide over 72 weeks. Results vary from person to person.
Which has fewer side effects, semaglutide or tirzepatide?
Their side effects are very similar, mostly nausea, diarrhea, vomiting and constipation. In SURMOUNT-5, fewer people stopped tirzepatide for stomach side effects (2.7%) than semaglutide (5.6%).
Why is tirzepatide more expensive?
It is a newer medicine that acts on two hormone receptors, and its makers price it higher. Insurance coverage and manufacturer programs can change what you actually pay, so check those first.
Can I switch from semaglutide to tirzepatide?
Yes, many people do, but only with your prescriber. There is no official dose conversion, so your prescriber picks your starting dose. Never take both at the same time.
What is the difference between compounded semaglutide and compounded tirzepatide?
They contain different molecules. Compounded semaglutide acts on GLP-1 only, and compounded tirzepatide acts on GIP and GLP-1. At Rx.com they start at $99 and $149 a month on a 12-month plan. Compounded medications are not FDA-approved.
How long does it take to reach the full dose?
On the labels, semaglutide reaches 2.4 mg after about 16 weeks of step-ups. Tirzepatide goes up in steps at least 4 weeks apart, so reaching 15 mg takes at least 20 weeks.
Is there a pill version of either drug?
Semaglutide comes as a daily tablet as well as a weekly shot. Tirzepatide is only available as an injection. See is there a tirzepatide pill for details.
Do I need to keep taking it to keep the weight off?
Usually, yes. Both work while you take them, and weight often returns after stopping. Plan for a medicine you can afford and tolerate over time.
Sources
- Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). New England Journal of Medicine, 2025. nejm.org
- American College of Cardiology. SURMOUNT-5: Greater Loss of Weight, Waist Circumference With Tirzepatide Than Semaglutide. acc.org
- Wegovy (semaglutide) prescribing information, including STEP 1 results. DailyMed, National Library of Medicine. dailymed.nlm.nih.gov
- Zepbound (tirzepatide) prescribing information, including SURMOUNT-1 results. DailyMed, National Library of Medicine. dailymed.nlm.nih.gov
- Eli Lilly and Company. Zepbound coverage and savings. zepbound.lilly.com
- Novo Nordisk. Price your Wegovy, NovoCare. novocare.com
- Centers for Medicare & Medicaid Services. Medicare GLP-1 Bridge. cms.gov
- U.S. Food and Drug Administration. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. fda.gov
- U.S. Food and Drug Administration. FDA's concerns with unapproved GLP-1 drugs used for weight loss. fda.gov
