Tirzepatide (Mounjaro for diabetes, Zepbound for weight loss) and semaglutide (Ozempic for diabetes, Wegovy for weight loss) are the two most widely used GLP-1-based weight loss medications. This comparison covers the key differences.
Mechanism
Ozempic/semaglutide: GLP-1 receptor agonist. Activates one receptor pathway involved in appetite regulation and blood sugar control.
Tirzepatide: Dual GIP/GLP-1 receptor agonist. Activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. The dual mechanism explains tirzepatide's stronger average weight loss outcomes.
Clinical Outcomes
Semaglutide STEP trials: 14.9% average weight loss at 68 weeks (2.4mg dose). About 1 in 3 patients lost 20% or more of body weight.
Tirzepatide SURMOUNT trials: 20.9% average weight loss at 72 weeks (15mg dose). About 57% of patients at maximum dose lost 20% or more of body weight.
Tirzepatide produces approximately 5–6% more average weight loss than semaglutide, which is clinically meaningful. However, both medications produce excellent outcomes compared to any prior weight loss medication.
Side Effects
Both have similar GI side effect profiles, nausea, constipation, diarrhea, and vomiting are the most common. Side effects are most pronounced during dose escalation and typically improve at stable doses. Tirzepatide may have a slightly higher rate of GI side effects at maximum doses, but most patients tolerate both well with proper dose escalation.
Dosing
Semaglutide (Wegovy): Weekly injection. Escalation from 0.25mg → 0.5mg → 1mg → 1.7mg → 2.4mg over 16 weeks.
Tirzepatide (Zepbound): Weekly injection. Escalation from 2.5mg → 5mg → 7.5mg → 10mg → 12.5mg → 15mg over 20 weeks.
Cost Comparison
| Medication | Brand Retail | Compounded (Telehealth) |
|---|---|---|
| Ozempic / Wegovy (semaglutide) | $900–1,050/mo | $147–200/mo |
| Mounjaro / Zepbound (tirzepatide) | $1,000–1,300/mo | $197–280/mo |
Which Should You Choose?
Both are excellent choices. Tirzepatide produces stronger average weight loss outcomes and is worth considering if that's a priority. Semaglutide is well-established with a longer track record at scale, and is typically $50–80/month less expensive through compounding pharmacies.
The best choice depends on your health history, physician's recommendation, and individual response. Some patients who plateau on semaglutide switch to tirzepatide with good results.