Semaglutide vs Tirzepatide Compared (2026)
Semaglutide vs Tirzepatide comparison: weight loss efficacy, mechanisms, side effects, dosing, and pricing.
Live Price Comparison
Prices updated automatically from verified vendors
| Metric | Semaglutide | Tirzepatide |
|---|---|---|
| Best Value (per mg) | $4.80/mg EZ Peptides — 10mg | $2.38/mg EZ Peptides — 60mg |
| Lowest Price | $35.00 EZ Peptides — 5mg | $44.00 EZ Peptides — 10mg |
| In-Stock Vendors | 5 offers | 11 offers |
| Available Sizes | 5mg, 10mg | 5mg, 10mg, 15mg, 20mg, 30mg, 60mg |
| Full Pricing | View all prices | View all prices |
The Two Most Effective Weight Loss Peptides
Semaglutide and Tirzepatide have transformed the weight loss landscape. Both are GLP-1 receptor agonists, but Tirzepatide adds a second mechanism — GIP receptor agonism — that may give it an edge in clinical trials.
This comparison covers the real differences backed by published trial data.
Mechanism of Action
Semaglutide (GLP-1 Agonist)
Semaglutide mimics the GLP-1 hormone, which is naturally released after eating. Effects include:
- Appetite suppression — acts on hypothalamic hunger centers
- Delayed gastric emptying — food stays in the stomach longer, increasing satiety
- Improved insulin sensitivity — reduces blood sugar spikes
- Reduced food reward signaling — decreases cravings and reward-driven eating
Semaglutide is a single agonist — it targets only the GLP-1 receptor.
Tirzepatide (Dual GIP/GLP-1 Agonist)
Tirzepatide activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors:
- GLP-1 effects — same appetite suppression and insulin sensitivity as semaglutide
- GIP receptor activation — enhances fat metabolism and insulin secretion through a complementary pathway
- Synergistic signaling — the dual mechanism produces greater metabolic effects than either pathway alone
This dual agonism is why Tirzepatide has shown superior weight loss in head-to-head trials.
Quick Comparison Table
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Mechanism | GLP-1 agonist | Dual GIP/GLP-1 agonist |
| FDA status | Approved (diabetes + weight loss + oral) | Approved (diabetes + weight loss) |
| FDA approved | Yes — weight loss & T2D | Yes — weight loss & T2D |
| Administration | Weekly injection (or daily oral) | Weekly injection |
| Oral option | Yes | No |
| Max clinical dose | 2.4 mg/week | 15 mg/week |
| Avg weight loss (trials) | ~15–17% body weight | ~20–22.5% body weight |
| Time to market | 2017 (T2D), 2021 (weight) | 2022 (T2D), 2023 (weight) |
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Clinical Trial Results
STEP Trials (Semaglutide)
The STEP program studied semaglutide 2.4 mg weekly in overweight/obese adults:
- STEP 1: 16.9% average weight loss over 68 weeks vs 2.4% placebo
- STEP 2 (T2D patients): 9.6% weight loss
- STEP 3 (with behavioral therapy): 16.0% weight loss
- STEP 5 (2-year data): 15.2% sustained weight loss
SURMOUNT Trials (Tirzepatide)
The SURMOUNT program studied tirzepatide at 5mg, 10mg, and 15mg weekly:
- SURMOUNT-1: 20.9% average weight loss at 15mg over 72 weeks vs 3.1% placebo
- SURMOUNT-2 (T2D patients): 14.7% at 15mg
- SURMOUNT-3 (with lifestyle intervention): 26.6% at highest dose
- SURMOUNT-4 (maintenance): continued weight loss vs weight regain on placebo
Head-to-Head
No large head-to-head trial has directly compared them at optimal doses for weight loss. However, cross-trial comparison consistently shows Tirzepatide producing 3–6% greater body weight reduction at maximum doses.
Side Effects Compared
Both share similar GI side effect profiles since they both activate GLP-1 receptors:
| Side Effect | Semaglutide | Tirzepatide |
|---|---|---|
| Nausea | ~44% (most common) | ~31% |
| Diarrhea | ~30% | ~23% |
| Vomiting | ~24% | ~12% |
| Constipation | ~24% | ~23% |
| Pancreatitis risk | Rare but monitored | Rare but monitored |
| Gallbladder events | Slightly elevated | Slightly elevated |
| Muscle loss | Concern at higher weight loss | Concern at higher weight loss |
Tirzepatide generally shows lower GI side effect rates in trials, possibly because GIP receptor activation provides a "smoother" signaling profile than pure GLP-1 agonism.
Muscle Loss Concern
Both peptides cause significant weight loss, and a portion of that weight is lean mass. This is a concern at higher doses and longer durations. Research suggests combining either peptide with resistance training and adequate protein intake to preserve muscle.
Dosing Comparison
Semaglutide
| Phase | Dose | Frequency |
|---|---|---|
| Week 1–4 | 0.25 mg | Weekly |
| Week 5–8 | 0.5 mg | Weekly |
| Week 9–12 | 1.0 mg | Weekly |
| Week 13–16 | 1.7 mg | Weekly |
| Maintenance | 2.4 mg | Weekly |
Tirzepatide
| Phase | Dose | Frequency |
|---|---|---|
| Week 1–4 | 2.5 mg | Weekly |
| Week 5–8 | 5.0 mg | Weekly |
| Week 9–12 | 7.5 mg | Weekly |
| Week 13–16 | 10 mg | Weekly |
| Maintenance | 10–15 mg | Weekly |
Both require gradual dose titration to minimize GI side effects.
Other Weight Loss Peptides
The GLP-1 space is rapidly evolving. Other peptides worth comparing:
- Liraglutide — daily GLP-1 agonist, less effective than both but FDA-approved since 2014
- Retatrutide — triple agonist (GLP-1/GIP/Glucagon), showing up to 24% weight loss in Phase 2 trials
- AOD-9604 — HGH fragment for fat metabolism, much milder effect
The Bottom Line
| If your situation is... | Consider |
|---|---|
| Maximum weight loss | Tirzepatide (superior trial data) |
| Need oral option | Semaglutide (oral formulation available) |
| GI sensitivity | Tirzepatide (lower side effect rates) |
| Longest safety track record | Semaglutide (on market longer) |
| Type 2 diabetes + weight loss | Either (both FDA-approved for T2D) |
| Cost sensitivity | Check live pricing above — varies by vendor and dose |
| Next-generation option | Watch Retatrutide (triple agonist) |
Tirzepatide has the edge in raw efficacy and tolerability based on trial data. Semaglutide has a longer track record and an oral formulation. Both are transformative — the choice depends on individual context.
Related Comparisons & Guides
- Retatrutide — The next-generation triple agonist (GLP-1/GIP/Glucagon) showing up to 24% weight loss
- AOD-9604 — HGH fragment for fat metabolism, a milder peptide option
- Liraglutide — The original daily GLP-1 agonist, FDA-approved since 2014
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- Ipamorelin vs GHRP-2 vs GHRP-6 — Growth hormone peptides that complement metabolic goals
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This article is for educational and research purposes only. It is not medical advice.