If you've started looking into medical weight loss in St. Louis, St. Charles County or Jacksonville, two names come up again and again: semaglutide and tirzepatide. Friends compare notes and ads make big promises, so it's hard to tell what actually matters.
This guide explains how each medication works, what the research shows, the side effects, the labs Summit Rejuvenation requires before either one, and the questions to bring to your provider. The right choice depends on your health, not on what worked for your neighbor.
The short version
- Both are prescription medications usually taken as a once-weekly injection under the skin, used along with a reduced-calorie diet and more physical activity.
- Semaglutide acts on one hormone pathway, GLP-1 (glucagon-like peptide-1). FDA-approved brands include Wegovy for weight management and Ozempic for type 2 diabetes. Wegovy is also available as an FDA-approved daily pill.
- Tirzepatide acts on two pathways, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). FDA-approved brands are Zepbound for weight management and Mounjaro for type 2 diabetes.
- Labs come first. At Summit, a provider consult and fasting labs are required before you start either medication. More on that below.
How each one works
GLP-1 is a hormone your gut releases after you eat. It helps signal fullness to your brain, slows how quickly your stomach empties and helps regulate blood sugar. Semaglutide is designed to act like GLP-1, so many people feel satisfied with smaller portions and notice fewer cravings.
GIP is another gut hormone involved in how your body handles food and blood sugar. Tirzepatide activates both the GLP-1 and GIP receptors. That dual action is the main thing that sets it apart from semaglutide.
Neither replaces the basics: what you eat, how you move and how you sleep still shape your results.
What the research shows
Both have been studied in large clinical trials, and both have FDA-approved uses beyond weight loss:
- Semaglutide (Wegovy) is also approved to reduce the risk of major cardiovascular events, such as heart attack and stroke, in adults with established heart disease and obesity or overweight. In 2025 it also received accelerated approval for a type of liver disease called MASH with moderate to advanced fibrosis.
- Tirzepatide (Zepbound) is also approved to treat moderate to severe obstructive sleep apnea in adults with obesity.
The two drugs were compared directly in a trial called SURMOUNT-5, published in the New England Journal of Medicine in 2025. It included 751 adults with obesity who didn't have diabetes. After 72 weeks, average weight loss was 20.2% with tirzepatide and 13.7% with semaglutide. The trial was funded by tirzepatide's manufacturer, and averages don't predict what any one person will experience. Some people tolerate one medication more easily than the other, and some aren't a good fit for either.
Side effects and safety
The side effects are similar. The most common are stomach-related: nausea, diarrhea, constipation, vomiting and reduced appetite. They tend to show up most when you start or when the dose goes up, which is why doses are increased gradually.
Less common but more serious risks are listed on both labels. They include pancreatitis, gallbladder problems, low blood sugar (especially with certain diabetes medications), kidney problems linked to dehydration and allergic reactions. Both medications also carry a boxed warning about thyroid C-cell tumors, which were seen in rodent studies. Neither should be used by anyone with a personal or family history of medullary thyroid carcinoma or with MEN 2 (multiple endocrine neoplasia syndrome type 2).
That's why medical supervision matters and the first step isn't a prescription.
The labs required before you start
At Summit, semaglutide and tirzepatide both require labs before you start. Your panel includes:
- Amylase and lipase, enzymes that help check your pancreas
- Insulin, which gives your provider a picture of how your body handles blood sugar
- Calcitonin, a marker tied to the thyroid C-cells mentioned in the boxed warning
These labs must be drawn after fasting for at least 6 to 8 hours. Your provider may add other markers based on your history. You can read more about how testing works on our bloodwork page.
A licensed provider reviews your results with you, together with your health history, current medications and goals, before anything is prescribed. If your labs or history point away from these medications, your provider will tell you and talk through other parts of a weight loss plan.
How to choose: questions to bring to your provider
There's no one-size-fits-all answer. These questions help you and your provider decide:
- What do my labs show? Your amylase, lipase, insulin and calcitonin results, plus your overall panel, are the starting point.
- What's in my personal and family history? Pancreatitis, gallbladder disease, thyroid cancer or MEN 2, and kidney problems all matter.
- What other medications do I take? Some diabetes medications raise the risk of low blood sugar with these drugs, and tirzepatide can make oral birth control less effective for a time after you start or raise the dose.
- What are my goals beyond the scale? Blood sugar, heart health, sleep apnea and energy may all point the conversation in one direction.
- What does the dosing schedule look like? Ask how often the dose goes up and what happens if side effects get in the way.
A note on compounded versions
You may see compounded semaglutide or tirzepatide advertised online or at med spas. Compounded versions are not FDA-approved. The FDA doesn't review compounded drugs for safety, effectiveness or quality before they're sold, and it has received reports of dosing errors with compounded GLP-1 products. They aren't the same as Wegovy, Ozempic, Zepbound or Mounjaro. Make sure any prescription is filled by a state-licensed pharmacy.
Protein and strength training: non-negotiable on either one
When appetite drops, it's easy to under-eat protein and skip workouts, which can mean losing muscle along with fat. A 2025 joint advisory from four obesity and nutrition organizations recommends that GLP-1 treatment be paired with adequate protein and regular strength training to help preserve muscle and bone.
In practice, that looks like:
- Build every meal around protein. Lean meat, fish, eggs, Greek yogurt, cottage cheese, beans and tofu are all good anchors. Eat the protein first if you fill up quickly.
- Lift on a schedule. The advisory suggests strength training at least three times a week, plus regular aerobic activity, adjusted to your fitness level.
- Hydrate. Water helps with constipation.
- Track more than weight. Strength, energy, how your clothes fit and your follow-up labs tell you more than the scale alone.
Summit's medical weight loss program includes coaching through our 1st Phorm partnership, with a coach, a trainer and app-based nutrition and workout guidance to help you keep muscle while you lose fat.
Where to start in St. Louis or Jacksonville
Summit has clinics in South County, Chesterfield, Wentzville and Cottleville in Missouri, and in Jacksonville, Florida. Learn more on our medical weight loss in Wentzville and medical weight loss in Jacksonville pages.
Telehealth is available 24/7, so many check-ins can happen from home. HSA and FSA cards are accepted.
Ready to talk it through? Book a consultation and a licensed provider will walk you through your labs and both options before you decide anything.
Frequently asked questions
What's the main difference between semaglutide and tirzepatide?
Semaglutide acts on one hormone pathway (GLP-1). Tirzepatide acts on two (GLP-1 and GIP). Both are usually taken as once-weekly injections for weight management alongside diet and activity changes.
Do I need labs before starting semaglutide or tirzepatide?
Yes. At Summit, a provider consult and labs are required before starting either medication. Your labs include amylase, lipase, insulin and calcitonin, drawn after fasting for at least 6 to 8 hours.
Which one causes more weight loss?
In the 2025 SURMOUNT-5 trial of adults with obesity and without diabetes, average weight loss at 72 weeks was 20.2% with tirzepatide and 13.7% with semaglutide. Individual results vary, and the best choice depends on your health history, labs and how you tolerate treatment.
Are compounded semaglutide and tirzepatide FDA-approved?
No. Compounded versions are not FDA-approved, and the FDA doesn't review them for safety, effectiveness or quality before they're sold. They aren't the same as Wegovy, Ozempic, Zepbound or Mounjaro.
Why do protein and strength training matter on these medications?
A lower appetite makes it easy to under-eat protein, which can lead to muscle loss along with fat loss. Eating enough protein and strength training at least three times a week helps preserve muscle and bone.
Can I do my visits by telehealth?
Yes. Telehealth is available 24/7, so many visits and check-ins can happen from home. Labs are drawn at a local lab, and you can also visit one of our clinics in Missouri or Jacksonville.
This article is for educational purposes only and isn't medical advice. Semaglutide and tirzepatide aren't appropriate for everyone. Talk with a licensed healthcare provider about your own health, risks and treatment options.
Reviewed by Summit Rejuvenation's licensed medical team.