Choosing Between Tirzepatide and Semaglutide: The Ultimate Guide
- Corinne Vangile, CHWC
- Apr 30
- 3 min read
Updated: 2 hours ago
Choosing between Semaglutide and Tirzepatide can be daunting. Both medications have made headlines for helping patients lose weight and improve metabolic health—but which one is right for you?

At Onyx Weight Loss Clinic, we specialize in personalized weight loss therapy and use both Semaglutide and Tirzepatide as part of our patient-centered weight loss programs. This blog will walk you through everything you need to know to make an informed decision with your provider.
What Are Semaglutide and Tirzepatide?
Both medications are GLP-1 receptor agonists, a class of drugs that mimic a natural gut hormone called glucagon-like peptide-1 (GLP-1). This hormone plays a major role in managing blood sugar, regulating appetite, and promoting fat loss.
Semaglutide:
Semaglutide is a GLP-1 receptor agonist. It mimics a natural hormone (GLP-1) that slows digestion, reduces appetite, regulates blood sugar, and supports steady, sustainable fat loss.
Tirzepatide:
A dual agonist that mimics both GLP-1 and GIP (Glucose-Dependent Insulinotropic Polypeptide).
How GLP-1 Works in the Body
When you eat, your gut naturally releases GLP-1, which helps:
Slow digestion and gastric emptying (keeping you full longer)
Signal satiety to the brain
Lower blood sugar by enhancing insulin release
But here’s the catch: Factors like ultra-processed diets, insulin resistance, chronic inflammation, and aging can reduce your body’s natural GLP-1 production, making it harder to manage appetite and weight.
Medications like Semaglutide and Tirzepatide restore this missing signal and give your metabolism the support it needs to function more efficiently.
What Makes Tirzepatide Different?
The key difference is GIP. Tirzepatide activates both GLP-1 and GIP receptors. Here's why that matters:
What GIP Does:
Stimulates insulin release (only when blood sugar is elevated)
Enhances insulin sensitivity in cells
Promotes fat metabolism
May help preserve lean muscle mass during weight loss
Helps regulate inflammation and gut hormone activity
By mimicking both GLP-1 and GIP, Tirzepatide creates a dual hormone approach that may offer more powerful and efficient fat loss—especially for people with insulin resistance or stubborn weight plateaus.
What We've Seen at Onyx Weight Loss Clinic
We’ve treated thousands of patients using both Semaglutide and Tirzepatide, and here’s what we’ve consistently seen:
✔️ Higher weight loss percentage on Tirzepatide
✔️ Less nausea and fatigue in patients who choose Tirzepatide
✔️ Great results for patients with PCOS, prediabetes, and stubborn midsection weight
✔️ Improved blood sugar and A1C labs
✔️ Positive shifts in mood, energy, and inflammation levels
While every patient’s journey is unique, most individuals at Onyx Weight Loss Clinic who have experienced both Semaglutide and Tirzepatide find they prefer Tirzepatide for its enhanced results and tolerability. That said, Semaglutide remains an excellent option for many, especially when combined with personalized nutrition coaching.
Side Effects: What to Expect
Both medications can cause:
Nausea
Bloating
Constipation or diarrhea
Fatigue
Appetite suppression
Tirzepatide’s dual mechanism may feel more “gentle” to some patients because GIP balances out some of the strong appetite-suppressant effects of GLP-1 alone.
At Onyx, we also offer microdosing plans, which can significantly reduce side effects while still providing great metabolic benefits for those with a BMI of 22-27.
Personalization Is Key
At the end of the day, the best medication is the one that fits your body and your lifestyle.
At Onyx Weight Loss Clinic, we evaluate your medical history and goals to create a dosing plan that best fits your needs.
We also recognize that sustainable, healthy weight loss isn’t just about medication—it’s about transforming your habits for life. That’s why we offer personalized nutrition coaching services with our certified nutrition coach, helping you make meaningful, lasting changes that support your long-term success.
Ready to Start?
Ready to start your personalized weight loss journey? Book a free consultation with one of our expert nurse practitioners today. We proudly serve clients across North Carolina, Virginia, Colorado, Pennsylvania, Maine, Vermont, New Hampshire, Nebraska, and Iowa.
Fact Checked: Tasha Vangile, FNP-C
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