Skip to content
The Peptide Effect
Comparison

Semaglutide vs Tirzepatide

Semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) are the two dominant FDA-approved peptides for weight loss and type 2 diabetes. Semaglutide is a pure GLP-1 receptor agonist, while tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist. Head-to-head trials (SURMOUNT and SURPASS programs) consistently show tirzepatide delivers superior weight loss (~22.5% vs ~15% body weight) and comparable or better glycemic control, though both represent a paradigm shift in obesity treatment.

Side-by-side comparison diagram of Semaglutide and Tirzepatide mechanisms of action
Conceptual comparison — not to scale

Head-to-Head Comparison

CriteriaSemaglutideTirzepatide
Primary mechanismGLP-1 receptor agonist (single incretin)Dual GIP and GLP-1 receptor agonist (twincretin)
Best forWeight loss, type 2 diabetes, cardiovascular risk reductionMaximum weight loss, type 2 diabetes, patients who plateau on semaglutide
Route of administrationOnce-weekly subcutaneous injection (also oral tablet for diabetes)Once-weekly subcutaneous injection
Typical dosage0.25 mg escalating to 2.4 mg weekly (Wegovy for weight loss)2.5 mg escalating to 5 mg, 10 mg, or 15 mg weekly
Average weight loss~15% of body weight at 68 weeks (STEP 1 trial)~22.5% of body weight at 72 weeks (SURMOUNT-1 trial)
Half-life~7 days (once-weekly dosing)~5 days (once-weekly dosing)
FDA statusApproved for obesity (Wegovy, 2021) and T2D (Ozempic, 2017)Approved for obesity (Zepbound, 2023) and T2D (Mounjaro, 2022)
Cardiovascular benefitProven 20% MACE reduction (SELECT trial)SURPASS-CVOT ongoing; expected cardiovascular benefit
Side effectsNausea (44%), vomiting (24%), diarrhea (30%), constipation (24%)Nausea (31%), vomiting (12%), diarrhea (23%), constipation (11%)
A1C reduction~1.5–1.8% average reduction~2.0–2.3% average reduction
Oral formulation available?Yes (Rybelsus 7 mg or 14 mg daily for T2D)Oral formulation in development (Phase 3)
Approximate monthly cost (US list price)$1,350–$1,430/month (brand)$1,060–$1,200/month (brand)

When to Choose Each

Choose Semaglutide

Patients wanting proven cardiovascular benefits, oral dosing option, or who respond well to GLP-1 monotherapy; also first-line for those with cardiovascular disease

Choose Tirzepatide

Patients seeking maximum weight loss, those who plateaued on semaglutide, better GI tolerability, or needing the most aggressive A1C reduction

Verdict

Tirzepatide delivers consistently greater weight loss than semaglutide in clinical trials — roughly 22.5% vs 15% body weight — and tends to produce fewer GI side effects at equivalent efficacy levels. However, semaglutide has a longer track record, proven cardiovascular outcomes data from the SELECT trial, and an oral option for patients who prefer pills. For pure weight loss maximization, tirzepatide is the stronger choice; for patients prioritizing cardiovascular risk reduction with robust long-term safety data, semaglutide remains the gold standard.

References

  1. Once-weekly semaglutide in adults with overweight or obesity (STEP 1) (2021) — PubMed
  2. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1) (2022) — PubMed
  3. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2) (2021) — PubMed
  4. Semaglutide and cardiovascular outcomes in patients with overweight or obesity (SELECT) (2023) — PubMed

Frequently Asked Questions

Can I switch from semaglutide to tirzepatide?
Yes, switching is common and generally done under physician supervision. Most protocols transition directly — for example, from semaglutide 2.4 mg to tirzepatide 2.5 mg, then titrate up. Many patients who plateau on semaglutide experience renewed weight loss after switching to tirzepatide due to the additional GIP receptor activity.
Which has fewer side effects — semaglutide or tirzepatide?
In head-to-head comparisons (SURPASS-2), tirzepatide generally produced comparable or slightly lower rates of nausea and vomiting at equivalent efficacy doses. Both medications cause GI side effects (nausea, diarrhea, constipation) during dose escalation, which typically subside after 4–8 weeks. Slow dose titration significantly reduces side effects for both.
Do you regain weight after stopping semaglutide or tirzepatide?
Yes, studies show significant weight regain after discontinuation of both medications. The STEP 1 extension trial showed two-thirds of weight loss was regained within one year of stopping semaglutide. Similar trends are expected with tirzepatide. Both are generally considered long-term or indefinite treatments for sustained weight management.
Are compounded versions of semaglutide and tirzepatide safe?
The FDA has issued warnings about compounded versions of both peptides. While compounding pharmacies can legally produce them during drug shortages, quality varies significantly. The FDA removed semaglutide from the shortage list in early 2024, creating legal uncertainty for compounded versions. Always verify that compounded products come from a 503B-registered outsourcing facility.
How do semaglutide and tirzepatide compare in cost?
At US list prices, both medications fall in a similar range: semaglutide (Wegovy) runs approximately $1,350 to $1,430 per month, while tirzepatide (Zepbound) costs roughly $1,060 to $1,200 per month. Actual out-of-pocket costs depend heavily on insurance coverage, manufacturer savings programs, and pharmacy. Compounded versions, where legally available, may cost $200 to $500 per month. On a cost-per-percent-body-weight-lost basis, tirzepatide may offer better value given its greater average efficacy. Discuss insurance coverage and affordability options with a healthcare provider.

Explore next