Semaglutide vs tirzepatide: how they differ

In short: Semaglutide acts on one gut-hormone receptor, GLP-1. Tirzepatide acts on two, GIP and GLP-1. Both are weekly injections with similar, mostly digestive side effects. Increase Health offers compounded semaglutide and compounded tirzepatide, which are not FDA-approved or FDA-reviewed. A licensed provider reviews your online intake and recommends one only if it suits you.

What is the difference between semaglutide and tirzepatide?

They work on different hormone signals. Semaglutide is a GLP-1 receptor agonist: it acts on the receptor for one gut hormone, GLP-1. Tirzepatide is a GIP and GLP-1 receptor agonist: it acts on the GLP-1 receptor and on a second one, for the hormone GIP¹². They are different medicines, not two brands of one drug.

Each has an FDA-approved brand for weight management: Wegovy (semaglutide) and Zepbound (tirzepatide). Both are approved for adults with obesity, or with overweight plus at least one weight-related health condition, alongside a reduced-calorie diet and more physical activity¹².

What Increase Health offers is compounded semaglutide and compounded tirzepatide. Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness or quality. A compounded medicine is not a generic of the brand³.

What did the head-to-head trial compare?

The SURMOUNT-5 trial, published in the New England Journal of Medicine in 2025, compared the two FDA-approved medicines directly in adults with obesity who did not have type 2 diabetes⁴. Its 751 participants were randomly assigned to one or the other and treated for 72 weeks. In that trial, tirzepatide led to greater average weight reduction than semaglutide⁴. Individual results vary.

What to know about the design:

• Randomized: chance decided who got which medicine, so the groups started out alike⁴.
• Open-label: participants and researchers knew which medicine each person was taking⁴.
• Funded by Eli Lilly, the maker of Zepbound⁴.
• Doses were adjusted during the trial to the highest level each person could tolerate⁴.
• Brand medicines only. The trial did not study compounded semaglutide or compounded tirzepatide, so its findings can't be applied to them. Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness or quality³⁴.

Do they have different side effects?

Their side effects are much the same. In trials of the FDA-approved medicines, the most common were digestive: nausea, diarrhea, vomiting and constipation, mostly mild to moderate and most likely while the dose was being raised⁴⁵⁶. In SURMOUNT-5, digestive effects were the most common in both groups⁴.

A few label differences:

• Both labels carry the same core warnings: the boxed warning about thyroid C-cell tumors, pancreatitis, gallbladder problems, low blood sugar with insulin or sulfonylureas, kidney injury from dehydration, severe stomach side effects, allergic reactions, diabetic eye disease and risks under anesthesia¹².
• The Wegovy label also warns that it can raise resting heart rate¹.
• The Zepbound label warns that it may make birth control pills less effective for a period after starting and after each dose increase².

Comparing side-effect rates across separate trials isn't reliable, so we don't. For what helps and when to get care, read our guide to GLP-1 side effects.

How are they taken?

Both are injected under the skin once a week. Your care team and its licensed providers will set the amount and when it changes, and it's printed on your prescription label. The brand medicines come in pens, and Zepbound also comes in vials¹². Follow your own label and the instructions that come with your order, not a friend's or a brand's.

• Inject under the skin of your belly, thigh or upper arm, rotating sites¹.
• Measure exactly what your label says, with the syringe supplied. FDA has reported serious measuring errors with compounded vials when "units", milliliters and milligrams were mixed up⁷. Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness or quality³.
• Our step-by-step guide covers measuring, sites and storage: How to give yourself an injection at home.

How does a provider choose between them?

There's no single right answer for everyone. A licensed provider looks at your medical history, current medicines, any past experience with a GLP-1 and how you tolerated it, your goals, and practical points like cost. They recommend a medicine only if treatment is appropriate for you, and they may recommend neither.

Things your care team and its licensed providers may weigh:

• Your health history. Thyroid cancer history (medullary thyroid carcinoma or MEN 2), past pancreatitis, gallbladder disease, severe gastroparesis, diabetic eye disease and other conditions all matter¹²⁸.
• Other medicines. Insulin or sulfonylureas raise the risk of low blood sugar. Birth control pills matter for tirzepatide¹².
• Pregnancy plans. Neither is for use in pregnancy. The Wegovy label says to stop at least two months before a planned pregnancy¹².
• How you did on one before. Side effects you had and how you tolerated them.
• Cost and availability. The two have different prices (see the table). Tell your care team if price matters to you.

Can I switch from one to the other?

Possibly, but it's a decision for your care team and its licensed providers. Don't switch, combine or convert doses on your own. The labels say not to use either medicine with another GLP-1 receptor agonist¹². If you're thinking about switching, message your care team. Its licensed providers will decide whether it makes sense and what to prescribe.

People often ask whether they'd have to "start over". That depends on your situation, and your care team and its licensed providers will explain their plan. Don't use online conversion charts. They will set the amount for whichever medicine you take.

How much do they cost through Increase Health?

As of September 2026, the 3-month starter price is $447 for compounded semaglutide and $669 for compounded tirzepatide. It's one payment with no subscription and no auto-renewal. Your card is authorized at checkout and charged only if a provider approves treatment. If you're not approved, you pay nothing.

• Klarna's four interest-free payments are available at checkout.
• The price covers your first three months. Ask your care team what later supplies cost.
• Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness or quality³.

Side by side

Side-effect findings come from trials of the FDA-approved brands, not from compounded products.

Questions to ask your care team when choosing

• Given my health history and medicines, is one of these a better fit for me, or neither?
• What side effects should I expect at first, and when should I contact you?
• I've taken one of these before. How does that change your recommendation?
• If I'm not getting on with my medicine, how would we decide whether to adjust or switch?
• Does either one interact with my birth control or my diabetes medicines?
• What will my treatment cost after the first three months?

What people often get wrong

• "Tirzepatide is just a stronger semaglutide." They're different medicines. Tirzepatide acts on a second hormone receptor, GIP, as well as GLP-1¹². "Stronger" isn't how providers choose; fit is.
• "The head-to-head trial proves compounded tirzepatide works better than compounded semaglutide." SURMOUNT-5 studied the FDA-approved brands only⁴. It tells us nothing about compounded products, which are not FDA-approved or FDA-reviewed for safety, effectiveness or quality³.
• "The one with bigger trial results must have worse side effects." Both had the same kind of side effects in their trials, mostly digestive and linked to dose increases⁴⁵⁶. Comparing rates across separate trials isn't reliable.
• "I can switch on my own using a conversion chart." Switching is a provider decision. The labels say not to combine either medicine with another GLP-1 medicine, and your care team and its licensed providers will set the amount for the one you take¹².
• "Compounded semaglutide is a generic Wegovy." No. Compounded medicines are not generics and are not FDA-approved³.