Semaglutide vs Tirzepatide: Which GLP-1 Wins on Weight Loss, Cost & Side Effects?

These are the two heavyweights of the GLP-1 world. Semaglutide (Ozempic, Wegovy) dominated the market first. Tirzepatide (Mounjaro, Zepbound) came later with even better weight loss numbers. But which one is actually right for you?

This guide compares them across what actually matters: effectiveness, cost, side effects, and availability.

The Head-to-Head Comparison

Effectiveness: The Clinical Data

Weight Loss Results

The SURMOUNT and STEP clinical trials provide clear data:

• Semaglutide 2.4mg (Wegovy): Average 15% body weight loss over 68 weeks
• Tirzepatide 15mg (Zepbound): Average 20.9% body weight loss over 72 weeks

For a 200-pound person, that's the difference between losing 30 pounds (semaglutide) vs 42 pounds (tirzepatide). The ~5% additional weight loss with tirzepatide is statistically significant and clinically meaningful.

Why Tirzepatide Works Better

Tirzepatide is a "dual agonist" — it activates both GLP-1 and GIP receptors. This dual mechanism appears to:

• Provide stronger appetite suppression
• Better regulate insulin sensitivity
• Potentially preserve more lean muscle mass during weight loss

Semaglutide only targets GLP-1 receptors. It's highly effective, but the single mechanism may explain the weight loss gap.

Blood Sugar Control

For diabetes patients, both medications dramatically improve A1C levels, but tirzepatide edges ahead:

• Semaglutide: 1.5-2.0% A1C reduction
• Tirzepatide: 2.0-2.3% A1C reduction

Cost Comparison: What You'll Actually Pay

Brand-Name Pricing

At list prices, they're similarly expensive. Semaglutide has a slight edge at self-pay manufacturer pricing:

• Wegovy/Ozempic (NovoCare): $349/month
• Zepbound/Mounjaro (LillyDirect): $399/month vials

Compounded Pricing

This is where semaglutide has a clear advantage. More compounding pharmacies produce it, creating competition:

• Compounded semaglutide: $149-249/month
• Compounded tirzepatide: $199-349/month

The $50-100/month savings with semaglutide adds up over time — $600-1,200/year — which may matter more than the ~5% weight loss difference for budget-conscious patients.

Side Effects: What to Expect

Both medications share similar GI side effects since they work through related pathways:

Common Side Effects (Both)

• Nausea (most common, typically improves over weeks)
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Decreased appetite (the intended effect)

Side Effect Severity

Clinical trials suggest tirzepatide may cause slightly more GI side effects at higher doses, but both are generally well-tolerated. Most side effects peak during dose escalation and improve with time.

Availability & Supply

Semaglutide currently has better supply chain stability:

• Semaglutide: Shortages largely resolved by 2025; consistent supply
• Tirzepatide: Intermittent shortages continue, especially at higher doses

Starting a medication and then being unable to refill it is frustrating and can impact results. Consider supply reliability when choosing.

Which Should You Choose?

Choose Semaglutide If:

• Budget is a primary concern (cheaper compounded options)
• You want a longer safety track record (FDA approved since 2017)
• Supply reliability matters to you
• 15% average weight loss meets your goals
• Your insurance covers Ozempic/Wegovy but not Mounjaro/Zepbound

Choose Tirzepatide If:

• Maximum weight loss is your priority
• You have significant insulin resistance or type 2 diabetes
• Cost is not a major factor
• Your insurance covers Mounjaro/Zepbound
• You haven't achieved desired results with semaglutide

The Practical Reality

For most people, the best GLP-1 is the one you can afford and access consistently. A 15% weight loss maintained over years beats a 20% weight loss you can't afford after 6 months.

Both medications are transformative. Don't agonize over the choice — pick based on your insurance, budget, and what's available, then commit to it long-term.

Switching Between Them

Some patients start with semaglutide (more affordable) and switch to tirzepatide if they plateau. This is a valid strategy, though:

• You'll restart dose titration with tirzepatide
• GI side effects may return during the transition
• Insurance may require re-authorization

Your provider can guide dosing equivalencies, though there's no perfect 1:1 conversion between the two medications.

The Bottom Line

Tirzepatide produces about 5% more weight loss than semaglutide in clinical trials. That's meaningful, but it comes with higher costs and potentially more supply issues.

Semaglutide offers a longer track record, better availability, and significantly lower prices — especially for compounded versions. For many patients, these practical advantages outweigh the incremental efficacy difference.

Both are excellent medications. Choose based on your budget, insurance, and access — then stick with it long enough to see results.