Semaglutide vs. Tirzepatide: Understanding the Key Differences

If you’ve been researching weight-loss medications, you’ve almost certainly heard of semaglutide and tirzepatide. Both of these medications can help people lose a significant amount of weight, but they work a little differently. 

At STL Medical Weight Loss, we offer both semaglutide and tirzepatide as part of our physician-supervised, medical weight loss programs. Understanding the differences between these two popular, effective medications helps ensure you get the best possible results.

GLP-1s: How semaglutide and tirzepatide work

Both semaglutide and tirzepatide mimic a hormone called glucagon-like peptide-1 (GLP-1). This hormone slows digestion so you feel full longer, and it also helps your body process blood sugar (glucose) more effectively. If you regularly battle feelings of hunger or intense cravings, these medications could be a game changer.

In addition to being a GLP-1 medication, tirzepatide also activates special nerve receptors for a hormone called glucose-dependent insulinotropic polypeptide (GIP), another hormone involved in blood sugar regulation and appetite. Because it works on both GLP-1 and GIP, tirzepatide can help some people achieve greater weight loss. 

For both medications, treatment typically starts at a lower dose and is gradually increased as your body adjusts to the medication’s effects. The goal is to find a dose that gives you healthy results that are right for you while minimizing potential side effects, like nausea, diarrhea, or constipation.

Differences to know about

Beyond the slight differences in how these medicines work, a few other factors matter, including how they’re administered. 

Currently, tirzepatide is only available as regular injections you perform yourself using a special self-injector. Semaglutide is also available as an injectable, but more recently, it’s also become available in pill form, too. That’s an important distinction if you’d really rather avoid injections.

What about weight loss?

For most people using weight loss medications, what matters most is how much weight they could potentially lose. Both medications support weight loss, but recent data show a significant difference in how much weight each can achieve.

That data comes from a study published in 2025 in the New England Journal of Medicine comparing both medicines in 751 adults with obesity but without Type 2 diabetes. Study participants received either medication for 72 weeks.

At the end of the study period, the researchers found those who took tirzepatide lost an average of 20.2% of their starting body weight, compared with 13.7% of those who took semaglutide. People taking tirzepatide also achieved a greater average reduction in waist circumference.

While those results are worth noting, remember the numbers in that study are averages, not guarantees. Your results depend on individual factors like your health history, lifestyle and fitness habits, starting weight, and how well your body responds to treatment. 

Choose a healthier future.

Bottom line: Tirzepatide and semaglutide are both effective options for medical weight management, but deciding which one is right for you isn’t just about which medication potentially achieves a higher average weight loss. Instead, the right choice depends on your health and your goals.

At STL Medical Weight Loss, our team can help you decide which approach is best for you. To explore your own options, call or book an appointment online with Joseph Moleski, DO, Laura Howard, FNP, and the team at STL Medical Weight Loss at our Chesterfield, Missouri, practice today. Can’t make it to the office? We also offer telehealth services for patients in Missouri, Texas, Illinois, Kansas, Florida, Delaware, Arizona, New York, Tennessee, Ohio, Michigan, Nevada, and Washington.