Semaglutide vs Tirzepatide: How to Choose

The DTC weight-loss conversation has flattened semaglutide and tirzepatide into a single “GLP-1” category. They're not the same medication. They work through different mechanisms, produce different magnitudes of effect, have different side-effect profiles, and fit different patients. Here's the decision framework Vektor's clinicians use.

What they actually are

Semaglutide (Wegovy, Ozempic) is a GLP-1 receptor agonist. It mimics the natural gut hormone GLP-1, which slows gastric emptying, increases satiety, and improves insulin sensitivity. Weekly subcutaneous injection.

Tirzepatide (Zepbound, Mounjaro) is a dual GLP-1 + GIP receptor agonist. It hits both receptors simultaneously, producing a stronger and more complete satiety + glycemic response. Also weekly subcutaneous injection.

Effect magnitude

Trial data is consistent: tirzepatide produces meaningfully more weight loss than semaglutide at therapeutic doses.

• Semaglutide — STEP-1 trial: ~15% body-weight reduction at 68 weeks (2.4mg/week dose)
• Tirzepatide — SURMOUNT-1 trial: ~20% body-weight reduction at 72 weeks (15mg/week dose)

That 5-percentage-point difference compounds. For a 220-lb patient: semaglutide → ~33 lb lost; tirzepatide → ~44 lb. The gap widens at the top dose.

Side effects

Both medications share the same primary side-effect profile: nausea (most common, usually peaks at dose-escalation), diarrhea, constipation, fatigue, occasional injection-site reactions. The frequency is comparable between the two.

Tirzepatide's GIP-receptor activation may produce slightly different metabolic side effects (some patients report better appetite control without the nausea peaks; others find it equivalent). Individual response varies considerably.

A practical decision framework

1. Start with insurance coverage if available. If your plan covers Wegovy or Zepbound for weight, the branded medication is the right answer regardless of which molecule. Insurance changes the math dramatically.
2. Otherwise, default to semaglutide for first GLP-1 patients. Longer track record in this demographic, simpler titration, generally well-tolerated. If satiety isn't adequate at the 1.7-2.4mg/week range, switch to tirzepatide.
3. Go directly to tirzepatide if your goal is >15% weight loss. The trial data is clear that tirzepatide produces larger weight reductions. If that's your target, starting on the stronger medication makes sense.
4. Cost matters when paying out-of-pocket. Compounded semaglutide ($179-299/mo through Vektor) is cheaper than compounded tirzepatide ($249-449/mo). Branded Wegovy and Zepbound are $1,029+/mo cash pay.

Compounded vs branded

Compounded semaglutide and tirzepatide are available through U.S. 503A pharmacies under specific medical-necessity criteria. The regulatory landscape has shifted year-to-year — compounded tirzepatide availability is more constrained than semaglutide in 2026. Your physician will walk through current options at the time of your protocol design.

How Vektor handles this

New GLP-1 patients in our practice get a 30-minute physician consult covering medication options, side-effect expectations, and a titration plan customized to their goals and lab values. Lab-led dose adjustment at week 6–8. Maintenance dose review at month 6. Patients can switch between semaglutide and tirzepatide based on response, with no fee for the protocol change — it's included in the $149/mo founding membership.