What SURMOUNT-5 actually measured
SURMOUNT-5 was the first head-to-head trial of the two leading weight-loss GLP-1s. Published in the New England Journal of Medicine in May 2025, it randomized 751 adults with obesity and no Type 2 diabetes to either tirzepatide (Zepbound, titrated to max 15mg) or semaglutide (Wegovy, titrated to max 2.4mg) for 72 weeks. The primary endpoint was percent change in body weight.
- Mean body-weight loss: Zepbound 20.2%, Wegovy 13.7%. Difference: 6.5 percentage points (p < 0.001).
- ≥15% weight loss: 64.6% Zepbound, 40.1% Wegovy.
- ≥25% weight loss: 31.6% Zepbound, 16.1% Wegovy.
- Discontinuation for GI adverse events: 6.1% Zepbound, 5.0% Wegovy — difference not statistically significant.
- Cardiovascular biomarkers (lipids, blood pressure, HbA1c): Both arms improved, Zepbound slightly more on HbA1c and triglycerides.
The cost-per-pound math (cash-pay, no coverage)
Take a 220-lb patient with no insurance coverage for AOM drugs. On 18 months of therapy (roughly the time to reach trial nadir weight):
- Wegovy via NovoCare vials: $499/mo × 18 = $8,982 total; expected loss ~30 lb (13.7% of 220) = $299 per pound. Note: NovoCare is only available for the 1.7mg and 2.4mg maintenance doses, so you’d need a separate cash-pay path (~$500/mo) for the first 16 weeks of titration before qualifying for vial pricing.
- Zepbound via LillyDirect vials: $349 × 4 + $499 × 14 = $8,382 total; expected loss ~44 lb (20.2% of 220) = $190 per pound.
The cost-per-pound delta ($109/lb) compounds over longer treatment windows. Over 3 years including titration and maintenance, Zepbound typically runs $6,000–$10,000 less in total drug cost for comparable weight outcomes.
Where Wegovy still wins
Wegovy has one clinical edge Zepbound hasn’t yet matched: the SELECT cardiovascular outcomes trial. SELECT (2023) demonstrated a 20% relative risk reduction in major adverse cardiovascular events (MACE — MI, stroke, CV death) in adults with established cardiovascular disease and overweight/obesity. This produced both an FDA indication expansion and Medicare Part D coverage for Wegovy in this narrow population. SURMOUNT-CV, tirzepatide’s CV outcomes trial, is enrolled but won’t read out until 2027.
If you have documented CVD (prior MI, stroke, stable angina, PAD) and overweight/obesity, Wegovy is the covered path on Medicare and has the outcomes data. Zepbound will likely catch up in 2027 but can’t yet claim CV risk reduction in labeling.
Coverage and payer behavior
Commercial insurance treats the two drugs similarly as of 2026. Roughly 40–50% of large-employer plans cover Wegovy for AOM indication; about 40–45% cover Zepbound. Both usually require prior authorization with BMI 30+ or 27+ with comorbidity, both land at Tier 3 specialty copay, both are eligible for manufacturer savings cards for the first 12 months of coverage.
The insurance coverage checker can give you a quick estimate by plan type. If you need to appeal a denial, the prior-auth guide with appeal checklist walks through the documentation that wins reviews.