Wegovy vs Zepbound: What's Actually Different

Wegovy and Zepbound get talked about like two flavors of the same shot. They aren't. Wegovy is semaglutide, made by Novo Nordisk; Zepbound is tirzepatide, made by Eli Lilly. They're different molecules with different mechanisms, different FDA-approved indications, and — as of a 2025 head-to-head trial — a measured difference in how much weight each one takes off. Here's what's actually different, sourced to the trial and the current labels rather than to brand marketing.

The head-to-head trial

For years, comparisons between semaglutide and tirzepatide for obesity relied on cross-trial comparisons — different studies, different populations, imperfect apples-to-apples. SURMOUNT-5 changed that: a phase 3b, open-label trial that randomized 751 adults with obesity (without type 2 diabetes) directly to tirzepatide or semaglutide, at each drug's highest approved doses, and followed them for 72 weeks¹. The result was decisive. Tirzepatide produced a mean weight reduction of 20.2% versus 13.7% for semaglutide (P<0.001), and waist circumference fell 18.4 cm versus 13.0 cm¹. Participants on tirzepatide were also more likely to reach every weight-loss milestone the trial tracked — 10%, 15%, 20%, and 25% — than those on semaglutide¹. Adverse events in both arms were predominantly gastrointestinal, mild to moderate, and concentrated during dose escalation — neither drug had a distinct safety signal the other lacked in this trial¹.

What each brand is actually approved to treat

This is where the two products have diverged furthest from "basically the same drug." Per Wegovy's current FDA label, semaglutide injection is approved for weight reduction, for reducing cardiovascular risk in adults with established cardiovascular disease and obesity or overweight, and — as of a newer indication — for treating noncirrhotic MASH (metabolic dysfunction-associated steatohepatitis) with moderate-to-advanced liver fibrosis². Wegovy is also now available as a tablet, not just an injection, in 1.5, 4, 9, and 25 mg strengths, alongside the injectable pens and prefilled syringes². Zepbound's current label, by contrast, adds a different indication: tirzepatide is FDA-approved to treat moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity, on top of its original weight-management approval³ — see GLP-1 and sleep apnea: the SURMOUNT-OSA trial evidence for the trial behind that approval. Neither drug's added indication is available on the other molecule as of this writing.

Same class, same core side-effect profile

Despite the different indications, both drugs share the class-wide gastrointestinal side-effect profile — nausea, vomiting, diarrhea, constipation — and the same boxed warning about thyroid C-cell tumors seen in rodent studies. We break down the full adverse-event tables from both labels in GLP-1 side effects: what the STEP and SURMOUNT trials actually reported and the boxed-warning language specifically in GLP-1 boxed warnings: what the label actually says.

The cash-pay comparison is a different question

Everything above concerns the FDA-approved brand-name products — what you'd typically get through insurance, a manufacturer program, or a brand-only pharmacy. If you're shopping cash-pay or compounded pricing instead, the value math runs differently and semaglutide is usually the lower-cost molecule; see semaglutide vs tirzepatide: the cheaper effective GLP-1 for that comparison, and semaglutide vs tirzepatide: comparing side effects and tolerability for a closer look at how the two drugs' adverse-event rates stack up dose by dose.

What this means if you're choosing between the brands

If your prescriber is deciding between Wegovy and Zepbound specifically — not the generic molecules, the branded, insurance-relevant products — three questions matter more than "which one is stronger": does your insurance formulary cover one and not the other, do you have a comorbidity (liver disease, sleep apnea) that one drug is specifically approved to treat, and does the SURMOUNT-5 effect-size gap justify Zepbound's typically higher list price for your goals. None of those questions has a universal answer — they depend on your coverage and your health profile, which is exactly why this belongs in a conversation with a prescriber rather than a brand preference.

Comparing what you'd actually pay

Brand-name pricing through insurance varies enormously by plan and formulary tier — sometimes dramatically more than the flat cash-pay rates we track. Compare cash-pay and program pricing for both molecules on our semaglutide price board and tirzepatide price board, and see how prescriber quality and program transparency factor into our scoring in the Value Score methodology. If Medicare coverage is part of your calculation, the new bridge program changes the math again — see the Medicare GLP-1 Bridge Program: what it actually covers in 2026.

This piece sits in our research index alongside every other sourced explainer we publish — the trials, the compounding rules and the pricing mechanics, grouped by the question each one answers.