Weight Loss Peptides: Complete Comparison

Choosing between Tirzepatide, Semaglutide, and Liraglutide? This comprehensive comparison covers efficacy, side effects, cost, dosing, and clinical evidence to help you make an informed decision.

All three are FDA-approved GLP-1 receptor agonists proven to produce significant weight loss. However, they differ in effectiveness, convenience, cost, and safety profiles.

Quick Comparison Table

Factor Tirzepatide Semaglutide Liraglutide
Brand Names Mounjaro, Zepbound Ozempic, Wegovy Victoza, Saxenda
Weight Loss 20-22% 15-17% 8-10%
Mechanism Dual GIP/GLP-1 GLP-1 only GLP-1 only
Dosing Weekly injection Weekly injection Daily injection
Half-Life 5 days 7 days 13 hours
FDA Approval 2022-2023 2021 2014
Clinical Data Newer, less long-term data Extensive, 5+ years Most established, 10+ years
Monthly Cost $1,000-1,400 $900-1,400 $1,300-1,500
Nausea Rate 25-30% 30-40% 35-45%
CV Benefits Under study Proven (SUSTAIN-6) Proven (LEADER)

Detailed Comparison

🏆 Tirzepatide (Mounjaro/Zepbound)

The newest and most effective option. Tirzepatide is a dual GIP/GLP-1 receptor agonist that produces superior weight loss compared to semaglutide in head-to-head trials.

Key Statistics

  • Weight Loss: 20-22% average (SURMOUNT-1 trial)
  • Dosing: 2.5mg → 5mg → 7.5mg → 10mg → 12.5mg → 15mg (weekly)
  • Titration: 20 weeks to reach maximum dose
  • FDA Approval: May 2022 (diabetes), November 2023 (weight loss)

✓ Advantages

  • Highest weight loss of any medication
  • Weekly injection (convenient)
  • Superior to semaglutide in SURMOUNT-2
  • May have better tolerability than semaglutide
  • Dual mechanism provides additional benefits

✗ Disadvantages

  • Newest option with less long-term data
  • Higher cost ($1,000-1,400/month)
  • Cardiovascular outcomes still under study
  • Limited availability/insurance coverage
  • Shortage issues in 2023-2024

💡 Best For:

Patients seeking maximum weight loss who are comfortable with a newer medication. Ideal if you've tried semaglutide with good results but want more efficacy, or if you experienced significant nausea on semaglutide.

🥇 Semaglutide (Ozempic/Wegovy)

The gold standard with extensive research. Semaglutide has the most clinical data, proven cardiovascular benefits, and a well-established safety profile.

Key Statistics

  • Weight Loss: 15-17% average (STEP trials)
  • Dosing: 0.25mg → 0.5mg → 1.0mg → 1.7mg → 2.4mg (weekly)
  • Titration: 16-20 weeks to reach maximum dose
  • FDA Approval: June 2021 (weight loss), 2017 (diabetes)

✓ Advantages

  • Extensive clinical data (5+ years)
  • Proven cardiovascular benefits (SUSTAIN-6)
  • Weekly injection (convenient)
  • Well-established safety profile
  • Better insurance coverage than tirzepatide
  • Oral version available (Rybelsus)

✗ Disadvantages

  • Less effective than tirzepatide
  • Higher nausea rate (30-40%)
  • Expensive ($900-1,400/month)
  • Shortage issues in 2022-2023
  • Slower titration schedule

💡 Best For:

Patients who want proven efficacy with extensive long-term data. Ideal if you have cardiovascular disease or risk factors, need established safety data, or want the option of oral administration (Rybelsus).

🥈 Liraglutide (Saxenda)

The most established option with daily dosing. Liraglutide was the first GLP-1 agonist approved for weight loss and has the longest safety track record.

Key Statistics

  • Weight Loss: 8-10% average (SCALE trials)
  • Dosing: 0.6mg → 1.2mg → 1.8mg → 2.4mg → 3.0mg (daily)
  • Titration: 5 weeks to reach maximum dose
  • FDA Approval: December 2014 (weight loss), 2010 (diabetes)

✓ Advantages

  • Most established (10+ years of data)
  • Proven cardiovascular benefits (LEADER)
  • Fastest titration (5 weeks)
  • Shorter half-life (easier to stop if needed)
  • Well-understood side effect profile

✗ Disadvantages

  • Lowest weight loss (8-10%)
  • Daily injection required (inconvenient)
  • Highest nausea rate (35-45%)
  • Most expensive ($1,300-1,500/month)
  • 365 injections per year vs 52 for weekly options

💡 Best For:

Patients who prioritize established safety data over maximum efficacy. Ideal if you're uncomfortable with newer medications, need the flexibility of a shorter half-life, or want the fastest titration schedule.

Head-to-Head Trial Results

SURMOUNT-2: Tirzepatide vs Semaglutide

The SURMOUNT-2 trial directly compared tirzepatide to semaglutide in patients with obesity and type 2 diabetes.

Outcome Tirzepatide 15mg Semaglutide 1mg Difference
Weight Loss -15.7% -9.3% +6.4% more
≥15% Weight Loss 51% 27% +24% more patients
≥20% Weight Loss 35% 14% +21% more patients
Nausea 25% 30% 5% less
Discontinuation 6.2% 5.3% Similar

Conclusion: Tirzepatide produced 69% more weight loss than semaglutide with similar or better tolerability.

Cost Comparison

Retail Pricing (Without Insurance)

Peptide Monthly Cost Annual Cost Cost per % Weight Loss
Tirzepatide $1,000-1,400 $12,000-16,800 $600-700 per %
Semaglutide $900-1,400 $10,800-16,800 $700-900 per %
Liraglutide $1,300-1,500 $15,600-18,000 $1,600-1,800 per %

⚠️ Insurance Coverage

Most insurance plans cover these medications for diabetes but NOT for weight loss alone. Coverage for weight loss typically requires:

  • BMI ≥30 or BMI ≥27 with comorbidities
  • Prior authorization
  • Documentation of failed diet/exercise attempts
  • Ongoing medical supervision

Copays with insurance: $25-250/month depending on plan.

Compounded Versions

Due to shortages, compounded versions of semaglutide and tirzepatide became available in 2022-2024 at significantly lower costs ($200-400/month). However:

Which Should You Choose?

Decision Framework

Choose Tirzepatide If:

  • You want maximum weight loss (20-22%)
  • You're comfortable with newer medications
  • You've tried semaglutide with good results but want more
  • You experienced significant nausea on semaglutide
  • Cost is not a primary concern

Choose Semaglutide If:

  • You want proven efficacy with extensive data (15-17%)
  • You have cardiovascular disease or risk factors
  • You prefer established medications with 5+ years of data
  • You want better insurance coverage
  • You're interested in oral administration (Rybelsus)

Choose Liraglutide If:

  • You prioritize safety data over maximum efficacy (8-10%)
  • You want the most established option (10+ years)
  • You need faster titration (5 weeks vs 16-20 weeks)
  • You prefer a shorter half-life for flexibility
  • You're okay with daily injections

💡 Can't Decide?

Most providers recommend starting with semaglutide as the best balance of efficacy, safety data, and cost. If results are insufficient after 6 months, switching to tirzepatide is straightforward.

Liraglutide is typically reserved for patients who specifically need daily dosing flexibility or have concerns about longer-acting medications.

Calculate Your Dosing Schedule → Read Getting Started Guide →

⚠️ Important Medical Disclaimer

This comparison is for educational purposes only and should not replace consultation with a qualified healthcare provider. The choice between these medications depends on your individual medical history, risk factors, insurance coverage, and personal preferences.

All three medications require prescription and medical supervision. They are not suitable for everyone and carry risks including pancreatitis, gallbladder disease, and thyroid tumors (in animal studies).