Semaglutide vs Tirzepatide: The Real Head-to-Head

If you're looking at GLP-1 medication, you've hit the fork in the road: semaglutide or tirzepatide?

Semaglutide = Wegovy/Ozempic. Tirzepatide = Zepbound/Mounjaro. Both produce serious weight loss. Both are weekly injections. Both have billion-dollar marketing budgets.

But they're not the same drug. Different mechanisms, different trial results, different trade-offs. Here's what the science actually says — not what the pharma marketing departments want you to think.

How Each One Works

Semaglutide: One Lever, Pulled Hard

Semaglutide is a GLP-1 receptor agonist. It mimics one gut hormone (glucagon-like peptide-1). That hormone slows gastric emptying, signals satiety to your brain, stimulates insulin, and suppresses glucagon.

Natural GLP-1 breaks down in minutes. Semaglutide is engineered to last a week.

New to GLP-1s? Start with our beginner's guide.

Tirzepatide: Two Levers

Tirzepatide is a dual GIP/GLP-1 receptor agonist — a "twincretin." It mimics two gut hormones instead of one:

• GLP-1 — same effects as above
• GIP (glucose-dependent insulinotropic polypeptide) — enhances insulin secretion, may improve fat metabolism, and amplifies appetite suppression

Tirzepatide isn't "stronger semaglutide." It's hitting a different biological pathway that produces additive effects. Two levers > one lever. The data backs this up.

Clinical Trial Numbers: Where It Gets Real

Semaglutide: STEP 1 Trial

• Participants: 1,961 adults, BMI 30+ (or 27+ with comorbidities)
• Duration: 68 weeks
• Average weight loss: 14.9% (vs 2.4% placebo)
• 69.1% lost 10%+
• 50.5% lost 15%+
• 32.0% lost 20%+

Groundbreaking when published. Nearly 15% from a weekly injection was unprecedented.

Tirzepatide: SURMOUNT-1 Trial

• Participants: 2,539 adults, BMI 30+ (or 27+ with comorbidities)
• Duration: 72 weeks
• Average weight loss at 15mg: 22.5% (vs 2.4% placebo)
• At 10mg: 21.4%
• At 5mg: 16.0%
• 56.7% lost 20%+ (at 15mg)
• 39.7% lost 25%+

Tirzepatide at the highest dose produced about 50% more weight loss than semaglutide. Even the lowest tirzepatide dose (5mg) slightly outperformed semaglutide 2.4mg.

Important caveat: These were separate trials, not a direct head-to-head. Different participant pools, different timelines (68 vs 72 weeks). A true head-to-head (SURMOUNT-5) has been completed with results expected in 2026. Preliminary data suggests tirzepatide maintains its advantage.

Side Effect Comparison

Here's a surprise — the side effect profiles are nearly identical:

Nausea is basically a coin flip at ~44% for both. GI symptoms are a wash. These percentages are "experienced at any point during the trial" — most side effects are worst during dose escalation and improve at maintenance dose.

For managing these, see our side effects guide.

Dosing Schedules

Semaglutide (Wegovy)

Time to maintenance: 16 weeks (4 months)

Tirzepatide (Zepbound)

Time to max dose: 20 weeks (5 months)

Providers who skip escalation steps are cutting corners. You'll "pay" for it with brutal nausea. Full semaglutide dosing guide here.

Pricing Comparison

Brand-Name (Without Insurance)

Plot twist: brand-name tirzepatide is actually cheaper than brand-name semaglutide. Eli Lilly has been pricing aggressively to grab market share.

Compounded (Cash-Pay Through Telehealth)

Compounded tirzepatide typically runs $50-100/month more than semaglutide because the API is more expensive to source.

For the cheapest options: pricing comparison across all providers.

Who Should Choose Which?

Go with semaglutide if:

• Budget is tight. $50-100/month cheaper compounded, adds up over a year.
• You want more safety data. On the market since 2021 vs 2023 for tirzepatide.
• Cardiovascular concerns. SELECT trial showed 20% reduction in cardiovascular events. Tirzepatide hasn't completed an equivalent trial yet.
• Your insurance covers Wegovy but not Zepbound.

Go with tirzepatide if:

• You want maximum weight loss. 22.5% vs 14.9% average. The data is clear.
• Significant insulin resistance or T2 diabetes. Dual mechanism = better blood sugar control.
• You plateaued on semaglutide. Switching to tirzepatide can break through.
• Your provider recommends it based on your metabolic profile.

The Bottom Line

Optimizing for max weight loss + can afford it? Tirzepatide wins. 22.5% body weight loss is hard to argue with.

Want the most established option with robust long-term data? Semaglutide is the safer bet in terms of track record.

But here's what actually matters: either one produces life-changing weight loss for most people who take it. The difference between 15% and 22% matters less than the difference between "I'm on treatment" and "I'm still thinking about it."

Talk to a provider. Pick one. Start. You can always adjust later.

For help choosing a provider: our provider selection guide or head-to-head reviews.