Bottom line
Zepbound (tirzepatide) produces the highest average weight loss of any FDA-approved GLP-1 — around 22% at 72 weeks. The dual GIP/GLP-1 mechanism explains the efficacy gap vs semaglutide.
Why dual-action works better
GLP-1 activation alone suppresses appetite. GIP adds insulin sensitization and fat storage regulation. Compounded effect, meaningfully stronger results.
The numbers
- Avg weight loss (72wk): ~22.5%
- Max dose: 15 mg/week
- Cash price 2026: $299-$499/mo
Side effects
Stronger action means stronger early side effects. Nausea at dose escalations is the #1 reason for slowing titration. A good program holds doses for an extra 4 weeks when needed.
Pipeline context
Retatrutide (Lilly's successor) is in Phase 3 with ~24% average weight loss. Starting Zepbound today isn't missing out, but 2027 will look different.