Semaglutide vs Tirzepatide for Weight Loss: Which Is Right for You?

Two medications now dominate the conversation around medical weight loss: semaglutide and tirzepatide. Both work by targeting gut hormones that regulate appetite and blood sugar. Both have impressive clinical trial data behind them.

So how do you know which one is right for you?

This guide lays out how each medication works, what the clinical data shows, where they differ, and how to think about the choice, without the hype.

> Important Notice: Compounded tirzepatide is currently on hold at Prescriva pending ongoing legal review. The regulatory pathway for compounding tirzepatide is extremely limited following the resolution of the FDA's shortage designation. This article discusses tirzepatide for educational purposes. Prescriva does not currently offer compounded tirzepatide. Please consult our care team for up-to-date availability information.

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How GLP-1 Medications Work

Before comparing the two, it helps to understand the shared foundation.

Your gut releases hormones after you eat, hormones that signal to your pancreas, your stomach, and your brain. Two of the most important for weight regulation are:

• GLP-1 (glucagon-like peptide-1): Released from the small intestine. Stimulates insulin release (when blood sugar is elevated), slows stomach emptying, and signals fullness to the brain.
• GIP (glucose-dependent insulinotropic polypeptide): Released from the upper small intestine. Also stimulates insulin release and, when targeted pharmacologically, appears to enhance the weight-loss effects of GLP-1 activation.

In people with obesity, these hormonal signals are often weakened or dysregulated. GLP-1 receptor agonist medications work by mimicking and amplifying these natural hormones, keeping the "I am full, stop eating" signal active far longer than your body would on its own.

The result: reduced hunger, smaller portions, and, over time, meaningful weight loss that is driven by biology rather than willpower alone.

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What Is Semaglutide?

Semaglutide is a GLP-1 receptor agonist. It targets only the GLP-1 receptor. It was first approved by the FDA for type 2 diabetes (as Ozempic, 2017) and later for chronic weight management (as Wegovy, 2021).

What the STEP 1 Trial Showed

The STEP 1 trial (Wilding et al., *NEJM*, 2021, PMID: 33567185) is the landmark study behind semaglutide's weight loss reputation. In this 68-week randomized controlled trial of brand-name semaglutide 2.4 mg weekly:

• Participants without diabetes lost an average of 14.9% of their body weight
• The placebo group lost an average of 2.4%
• 86% of semaglutide participants achieved at least 5% weight loss
• More than half (50.5%) achieved 15% or more weight loss

These are significant, clinically meaningful results. These results are from clinical trials of brand-name semaglutide and may not reflect results with compounded formulations. Results may vary.

How Semaglutide Is Dosed

Semaglutide for weight loss is typically dosed as a once-weekly subcutaneous injection, starting at 0.25 mg and gradually increasing to a maintenance dose of 2.4 mg over approximately 16-20 weeks.

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What Is Tirzepatide?

Tirzepatide is a dual GIP/GLP-1 receptor agonist, a meaningful distinction. Where semaglutide activates one receptor (GLP-1), tirzepatide activates two: both GIP and GLP-1 receptors simultaneously.

This dual mechanism appears to produce greater weight loss in clinical trials than single-receptor agonism alone.

A 2022 review by Frías et al. in *Cardiovascular Diabetology* (PMID: 36050763) described tirzepatide's dual mechanism as producing a synergistic metabolic effect beyond what either receptor pathway alone would achieve, enhancing insulin sensitivity, reducing fat mass, and amplifying appetite suppression through complementary pathways.

Tirzepatide was FDA-approved for type 2 diabetes (as Mounjaro, 2022) and for chronic weight management (as Zepbound, 2023).

What the SURMOUNT-1 Trial Showed

The SURMOUNT-1 trial (Jastreboff et al., *NEJM*, 2022, PMID: 35658024) is tirzepatide's landmark weight loss study. In this 72-week randomized controlled trial in adults with obesity:

• Average weight loss at 15 mg dose: 22.5% of body weight
• Placebo group: 2.4%
• At the highest dose, nearly a quarter of participants' body weight was lost on average

These results are from clinical trials of brand-name tirzepatide (Zepbound/Mounjaro) and may not reflect results with compounded formulations. Results may vary.

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Head-to-Head Comparison

*Compounded medications are not FDA-approved. Results may vary. Clinical trial figures are from studies of brand-name medications.*

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Who Should Choose Semaglutide?

Semaglutide may be the better starting point if you:

• Are new to GLP-1 therapy and want to start with the medication that has the longest clinical track record
• Prefer having an option with accessible, transparent pricing
• Are managing type 2 diabetes and want a well-studied option at that indication
• Are working within a tighter monthly budget

Semaglutide is not a "lesser" medication. For many people, the clinical results from STEP 1 trials represent exactly the outcome they are looking for.

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Tirzepatide: Educational Overview

Tirzepatide has shown superior weight loss in clinical trials compared to semaglutide. Head-to-head data (SURMOUNT-5) showed tirzepatide producing approximately 20% greater relative weight loss than semaglutide. In SURMOUNT-1, 37% of participants at the highest dose achieved 25% or more weight loss, outcomes previously associated only with surgical approaches.

However: Prescriva does not currently offer compounded tirzepatide. Following the FDA's resolution of the tirzepatide shortage designation and subsequent court rulings, the legal pathway for compounding tirzepatide has become extremely limited. We are monitoring legal developments and will update availability accordingly.

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Cost: Prescriva Semaglutide Pricing

Compounded semaglutide at Prescriva starts at $159/month, all-inclusive: consultation, medication, and shipping billed as a single monthly charge.

Brand-name semaglutide (Wegovy) carries a list price of approximately $1,349/month without insurance. Brand-name tirzepatide (Zepbound) runs approximately $1,060/month. Prescriva's compounded semaglutide program offers a dramatically more accessible entry point.

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How to Decide: Talk to a Provider

Both medications have nuances, drug interactions, contraindications, and individual health factors that matter. Prescriva's licensed providers will review your health history and recommend the option that fits your specific situation.

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FAQ

Is one medication safer than the other?

Both medications have similar side effect profiles, primarily gastrointestinal effects like nausea, diarrhea, and constipation, most pronounced in early weeks of treatment. Both carry the same boxed warning regarding thyroid C-cell tumors (based on animal data) and are contraindicated in people with a history of medullary thyroid carcinoma or MEN 2. This is not medical advice. Consult your healthcare provider.

Does insurance cover compounded semaglutide or tirzepatide?

Compounded medications are generally not covered by insurance. Prescriva's programs are designed as transparent out-of-pocket options for people who want accessible, predictable pricing.

Is tirzepatide actually better than semaglutide?

In clinical trials, tirzepatide produced greater average weight loss than semaglutide. A head-to-head trial (SURMOUNT-5) also showed greater weight loss with tirzepatide. "Better" depends on your goals, your health history, your tolerance for side effects, and your budget. Results may vary. Individual results depend on adherence to treatment and lifestyle changes. Clinical trial figures are from branded drug studies.

What are the side effects of both medications?

The most common side effects are the same for both: nausea, vomiting, diarrhea, and constipation. These are most pronounced in the first few weeks as your body adjusts to the medication. Serious but rare risks include pancreatitis, gallbladder disease, and, based on animal studies, thyroid C-cell tumors. Both medications are contraindicated in people with a history of medullary thyroid carcinoma or MEN 2.

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Medical Disclaimer

*Compounded medications are not FDA-approved. Compounded semaglutide is not the same as Ozempic or Wegovy and should not be considered equivalent to any FDA-approved product. Results may vary. Individual results depend on adherence to treatment and lifestyle changes. This article is for informational purposes only and does not constitute medical advice. Consult your healthcare provider before starting any new medication or weight loss program.*

*Clinical trial data cited (STEP 1, SURMOUNT-1) is from studies of FDA-approved brand-name medications. These results may not reflect outcomes with compounded formulations.*

*Ozempic and Wegovy are registered trademarks of Novo Nordisk A/S. Mounjaro and Zepbound are registered trademarks of Eli Lilly and Company. Prescriva is not affiliated with, endorsed by, or sponsored by these companies.*

Sources

1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). *New England Journal of Medicine.* 2021 doi:10.1056/NEJMoa2032183
2. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). *New England Journal of Medicine.* 2022 doi:10.1056/NEJMoa2206038
3. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes. *Cardiovascular Diabetology.* 2022 doi:10.1186/s12933-022-01580-y