How does semaglutide (Wegovy) help with weight loss?

Semaglutide is a GLP-1 receptor agonist that mimics a natural hormone your body releases after you eat. GLP-1 receptors are found in the brain, stomach, intestines, and pancreas. By activating these receptors, semaglutide reduces appetite, helps you feel full sooner, slows gastric emptying, improves blood-sugar control, and reduces cravings, making it easier to eat less without feeling deprived.

How does tirzepatide (Zepbound) work differently from semaglutide?

Tirzepatide is a dual GIP/GLP-1 receptor agonist, meaning it targets two hormones instead of one. Like semaglutide, it activates GLP-1 receptors to reduce appetite and improve blood-sugar control. It also activates GIP receptors in the pancreas, fat tissue, and brain regions involved in appetite and insulin regulation. Acting on both systems at once supports stronger appetite control, more stable blood sugar, and greater overall weight loss compared with GLP-1–only medications.

How do I choose between tirzepatide and semaglutide?

Choosing between tirzepatide and semaglutide depends on your weight-loss goals, medical history, budget, and how you respond to treatment. Semaglutide is a well-studied, highly effective GLP-1 medication and is often the best starting point, especially for cost-conscious patients. Tirzepatide may be preferred if you have more weight to lose, have plateaued on semaglutide, or want the maximum possible weight loss from a dual GIP/GLP-1 approach. A physician can review your history, adjust dosing, and help you decide which is best for you.

Do I need physician supervision for GLP-1 and GIP weight-loss medications?

Yes. Medications like semaglutide and tirzepatide work best and safest under physician supervision. Proper medical oversight includes selecting the right candidate, checking for contraindications, choosing an appropriate starting dose, gradually titrating the dose, managing side effects, and providing nutrition and lifestyle guidance. At Potere Health MD, patients receive individualized titration, regular check-ins, and support to ensure their weight loss is safe, effective, and sustainable.

Zepbound (Tirzepatide) vs. Wegovy (Semaglutide): Which Weight-Loss Medication Is Right for You?

Q: Which works better for weight loss — tirzepatide or semaglutide?

Both tirzepatide (Zepbound) and semaglutide (Wegovy) are highly effective weight-loss injections. In clinical trials, tirzepatide produced about 15% to 22.5% total body weight loss depending on the dose, while semaglutide 2.4 mg produced about 14.9% total body weight loss. On average, tirzepatide leads to roughly 5–10% more total body weight loss than semaglutide, but both medications are very effective when dosed and monitored correctly.

Q: Do patients tolerate tirzepatide better than semaglutide?

Both tirzepatide and semaglutide can cause gastrointestinal side effects such as nausea, fullness, bloating, constipation, or reflux. However, many patients—including those treated at Potere Health MD—report that tirzepatide feels smoother and that side effects are easier to tolerate once they reach the right dose. Emerging research suggests that activation of the GIP receptor may help offset some GLP-1–related nausea, and clinical trials show comparable or lower nausea rates with tirzepatide despite greater weight loss. Slow, personalized dose titration is important for both medications.

Q: Is tirzepatide more expensive than semaglutide?

Yes. In general, tirzepatide (Zepbound) is typically more expensive than semaglutide (Wegovy). Semaglutide is often the more budget-friendly option, and many patients start with semaglutide for cost reasons and later switch to tirzepatide if their goals require additional weight loss. Exact costs depend on your insurance coverage, self-pay pricing, and whether compounded options are available through your clinic.

Joshua Silva, MD
4 days ago
5 min read

If you’re comparing Zepbound (tirzepatide, GLP-1/GIP) vs. Wegovy (semaglutide, GLP-1) for weight loss, you’re not alone. These two medications are the most effective weight-loss injections available today — and both can help you lose significant weight safely under physician supervision.

This guide breaks down how each medication works, how they differ, which one produces more weight loss, what side effects to expect, and how to choose the option that fits your goals, budget, and health.

What Is Semaglutide (Wegovy)?

How Semaglutide Works (Mechanism of Action)

Semaglutide is a GLP-1 receptor agonist, a medication that mimics the hormone GLP-1 (glucagon-like peptide-1) your body naturally releases after you eat. GLP-1 receptors are found in the brain regions that control hunger, and throughout the stomach, intestines, and pancreas — allowing semaglutide to impact appetite, digestion, and blood-sugar regulation at the same time.

Semaglutide helps with weight loss by:

• Reducing appetite• Helping you feel full sooner

• Slowing gastric emptying (digestion)

• Improving blood-sugar control

• Reducing cravings and overeating

In simple terms: semaglutide helps you eat less without feeling deprived, making long-term weight loss much more achievable.

What Is Tirzepatide (Zepbound)?

How Tirzepatide Works (Mechanism of Action)

Tirzepatide is a dual GIP/GLP-1 receptor agonist — meaning it works on two appetite-regulating hormones instead of one.

It activates:

• GLP-1, just like semaglutide

• GIP (glucose-dependent insulinotropic polypeptide), a second hormone involved in appetite, insulin regulation, and fullness

Because tirzepatide acts on two hormonal pathways, many patients experience:

• Stronger appetite control

• More stable blood sugar

• Greater total weight loss

• Better control over cravings

Think of tirzepatide as a double-pathway medication that supports weight loss from multiple angles.

In addition to acting on GLP-1 receptors, tirzepatide also targets GIP receptors located in the pancreas, adipose (fat) tissue, and brain regions involved in eating behavior and insulin regulation.

By acting on both systems at once, tirzepatide can deliver stronger effects on appetite, fullness, and metabolic health than GLP-1 medications alone.

Tirzepatide helps with weight loss by:

• Reducing appetite and cravings

• Improving fullness after meals

• Stabilizing blood sugar

• Supporting healthier insulin responses

What about its effects on fat cells?

The GIP pathway does not make fat cells “burn fat faster.” Instead, early research suggests that tirzepatide helps fat tissue function more normally — reducing inflammation, improving adipocyte insulin responsiveness, and increasing adiponectin, a hormone linked to healthier metabolic regulation.

By improving insulin sensitivity, tirzepatide lowers the amount of insulin your body needs. Lower insulin levels reduce the hormonal signal that drives fat storage, making weight loss easier and more sustainable.

In simple terms: tirzepatide provides a “dual-action” effect — helping the brain, gut, and fat tissue work together — which contributes to the greater weight-loss results many patients experience.

Which Works Better for Weight Loss — Tirzepatide or Semaglutide?

Most high-quality research shows clear differences in average weight loss:

Tirzepatide (Zepbound)

• In large clinical trials (SURMOUNT-1), tirzepatide produced 15% to 22.5% total body weight loss, depending on the dose<sup>4</sup>.

Semaglutide (Wegovy)

• In the pivotal STEP-1 trial, semaglutide 2.4 mg produced ~14.9% total body weight loss, significantly greater than placebo<sup>5</sup>.

Bottom line in plain language:

Both medications work extremely well — but tirzepatide generally leads to 5–10% more total body weight loss than semaglutide.

Both medications require gradual dose escalation and consistent weekly dosing to be effective and well-tolerated.

What We See at Potere Health MD

Based on our clinical experience, tirzepatide may be especially helpful for:

• Patients with more weight to lose

• Patients who plateau on semaglutide

• Patients with strong appetite or craving patterns

• Patients who want the maximum possible weight loss

That said, many patients meet their goals on semaglutide, especially with physician-guided dosing, personalized nutrition, and proper titration.

Side Effects: Tirzepatide vs. Semaglutide

Both medications can cause similar mild gastrointestinal symptoms:

• Nausea

• Fullness

• Bloating

• Constipation

• Reflux

• Fatigue (occasionally)

These usually improve as your body adjusts.

Do Patients Tolerate Tirzepatide Better?

Many patients — including those treated at Potere Health MD — report that tirzepatide feels smoother and that side effects are easier to tolerate once they reach the right dose.

Emerging research shows that activation of the GIP receptor may help offset some of the nausea and GI discomfort associated with GLP-1–only medications. Preclinical studies demonstrate GIP signaling can attenuate GLP-1-induced nausea pathways. Clinical trials of tirzepatide also show comparable or lower nausea rates despite greater weight loss.

This improved comfort may be related to:

• More balanced hormonal signaling (GLP-1 + GIP)

• GIP activity that may reduce GLP-1-related nausea

• Smoother appetite regulation at equivalent weight-loss levels

Personalized dosing and slow titration are essential for both medications.

Cost Comparison: Zepbound vs. Wegovy

While exact pricing varies, here is what most patients can expect:

• Tirzepatide (Zepbound) is typically more expensive

• Semaglutide (Wegovy) is generally the more affordable option

Many patients begin with semaglutide for cost reasons and later switch to tirzepatide if their goals require it.

How to Choose Between Tirzepatide and Semaglutide

Here’s a simple decision guide we use at Potere Health MD:

Semaglutide (Wegovy) May Be Best If You Want:

• A highly effective, well-studied GLP-1 medication

• A more affordable option

• A great starting point if you’re new to weight-loss injections

• Strong appetite reduction with fewer upfront costs

Tirzepatide (Zepbound) May Be Best If You Want:

• Maximum possible weight loss

• Faster and stronger appetite control

• A medication with dual action (GLP-1 + GIP)

• A good option after semaglutide plateaus

• You tolerate GLP-1 therapy well and want a next-level result

The “best” medication depends on your goals, medical history, budget, and response.

Why Physician-Supervised Treatment Matters

Medications like semaglutide and tirzepatide work best when paired with:

• Correct dosing

• Side-effect management

• Nutrition guidance

• Real medical oversight

At Potere Health MD, we provide:

• Individualized titration

• Monthly check-ins

• Guidance on nausea prevention and meal size

• Support for long-term success and maintenance

This ensures safe, effective, and sustainable weight loss — not a short-term fix.

“A thoughtful woman looks to the side while comparing two weight-loss medications. On the right is a tirzepatide vial labeled GLP-1/GIP with checkmarks for ‘Better Results’ and ‘Less Side Effects.’ Below it is a semaglutide vial labeled GLP-1 with a checkmark for ‘Cost-effective.’”

Final Takeaway

Both Zepbound (tirzepatide) and Wegovy (semaglutide) are powerful and highly effective weight-loss medications.

• Semaglutide is an excellent, proven, cost-friendly option.

• Tirzepatide often delivers greater weight loss thanks to its dual-hormone mechanism.

With personalized dosing and physician guidance, you can achieve the results you’re looking for — safely and confidently.

If you’re unsure which option is right for you, we’re here to help you choose the medication that fits your health, goals, and budget.

Disclaimer:

This article is for educational purposes only and is not a substitute for medical advice.

About the Author

Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. He completed residency training in Occupational and Environmental Medicine from the University of Utah where he also earned a master's degree in Occupation Health. He now specializes in evidence-based weight management, including GLP-1/GIP therapies (semaglutide & tirzepatide). Dr. Silva provides in-person and virtual care for patients throughout Utah.

Sources:

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2. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab.2013;17(6):819-837. doi:10.1016/j.cmet.2013.04.008.https://pubmed.ncbi.nlm.nih.gov/23684623/

3. Regmi A, Aihara E, Christe ME, et al. Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor. Cell Metab. 2024;36(7):1534-1549.e7. doi:10.1016/j.cmet.2024.05.010.https://pubmed.ncbi.nlm.nih.gov/38878772/

4. Borner T, Geisler CE, Fortin SM, et al. GIP receptor agonism attenuates GLP-1 receptor agonist–induced nausea and emesis in preclinical models. Diabetes. 2021;70(11):2545-2553. doi:10.2337/db21-0459.https://pubmed.ncbi.nlm.nih.gov/34380697/

5. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038.https://pubmed.ncbi.nlm.nih.gov/35658024/

6. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP-1). N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183.https://pubmed.ncbi.nlm.nih.gov/33567185/