Semaglutide vs Tirzepatide
The two leading GLP-1 medications compared head to head
Semaglutide
GLP-1 receptor agonistTirzepatide
Dual GIP/GLP-1 receptor agonistHow They Work
Semaglutide
Mimics the GLP-1 hormone to reduce appetite and slow gastric emptying.
Tirzepatide
Activates both GIP and GLP-1 receptors, affecting appetite, insulin secretion, and fat metabolism.
Weight Loss Efficacy
STEP 1 trial: 14.9% weight loss vs 2.4% with placebo at 68 weeks, counting everyone who started (16.9% estimated assuming everyone stayed on treatment; n=1,961)
SURMOUNT-1 trial: 20.9% weight loss (15 mg) vs 3.1% with placebo at 72 weeks, counting everyone who started (22.5% estimated assuming everyone stayed on treatment; n=2,539)
Side Effects
Semaglutide
- Nausea (44%)
- Diarrhea (30%)
- Vomiting (24%)
- Constipation (24%)
- Abdominal pain (20%)
Tirzepatide
- Nausea (33%)
- Diarrhea (25%)
- Vomiting (17%)
- Constipation (20%)
- Injection site reactions (7%)
Cost Comparison
| Cost type | Semaglutide | Tirzepatide |
|---|---|---|
| Without Insurance | SemaglutideAbout $1,349/month list (Wegovy). NovoCare self-pay $349/month for the pens | TirzepatideList price $499 to $1,086.37 per fill by product and dose (Lilly, WAC January 1, 2026); LillyDirect self-pay from $299 for a 28-day supply, by dose |
| With Insurance | SemaglutideDepends on your plan. For eligible patients with commercial insurance, the Wegovy savings offer can lower the cost to as little as $25/month; savings are capped at $100/month | TirzepatideDepends on your plan. For eligible patients whose commercial plan covers the Zepbound single-dose pen, the Lilly savings card can lower the cost to as little as $25/month; savings are capped at $100/month |
| Compounded | SemaglutideNot FDA-approved. Since the shortage ended, compounding pharmacies generally may not make copies of the brand drug. See the FDA note below the table. | TirzepatideNot FDA-approved. Since the shortage ended, compounding pharmacies generally may not make copies of the brand drug. See the FDA note below the table. |
Compounded versions are not FDA-approved. Since the semaglutide and tirzepatide shortages ended, a state-licensed 503A pharmacy generally may not regularly make copies of these drugs. One exception applies when the prescriber determines that a change produces a significant difference for an identified individual patient; large 503B outsourcing facilities face separate, stricter limits. Source: FDA compounding policy statement, updated April 1, 2026.
Pros & Cons
Semaglutide
Advantages
- Longer track record of clinical use
- More published long-term safety data
- Available in oral form (Rybelsus) for diabetes
- Widely covered by insurance for weight loss (Wegovy)
Considerations
- Slightly less weight loss than tirzepatide in head-to-head trials
- Single-hormone mechanism (GLP-1 only)
- Common GI side effects during dose escalation
Tirzepatide
Advantages
- Greater average weight loss in clinical trials
- Dual-hormone mechanism may improve metabolic outcomes
- Slightly lower nausea rates than semaglutide
- Lower list price than Wegovy
Considerations
- Newer medication with less long-term safety data
- Insurance coverage still catching up (especially for Zepbound)
- No oral formulation available
- Compounded versions face FDA scrutiny
The Bottom Line
Both are highly effective for weight loss. Tirzepatide shows greater average weight loss in trials (20-22% vs 15-17%), but semaglutide has a longer safety track record and broader insurance coverage. Your provider will consider your medical history, insurance, and treatment goals when recommending one over the other.
Frequently Asked Questions
In head-to-head clinical trials, tirzepatide produced greater average weight loss. However, "better" depends on your individual response, insurance coverage, side effect profile, and medical history. Both are effective options.
Yes, switching is possible under medical supervision. Your doctor will typically start you at a lower dose of the new medication and adjust gradually. Do not switch medications without consulting your provider.
Both have similar gastrointestinal side effects (nausea, diarrhea, constipation). Tirzepatide may have slightly lower nausea rates based on trial data, but individual responses vary significantly.
Compounded medications are not FDA-approved. Since the semaglutide and tirzepatide shortages ended, a state-licensed 503A pharmacy generally may not regularly make copies of these drugs. One exception applies when the prescriber determines that a change in the compounded version produces a significant difference for an identified individual patient. Large 503B outsourcing facilities face separate, stricter limits. Ask your doctor about FDA-approved options first.
Source: FDA compounding policy statement, updated April 1, 2026
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See allMedical Disclaimer: This comparison is for informational purposes only and is not medical advice. All clinical data is sourced from FDA prescribing information and published peer-reviewed trials. Individual results vary. Always consult a qualified healthcare provider before starting, stopping, or switching any medication.