Zepbound vs Rybelsus: Weight Loss, Side Effects, Price
Zepbound (tirzepatide) and Rybelsus (semaglutide) are both GLP-1 medicines, weekly injection versus daily tablet. Zepbound self-pay starts at $299 per month.
A quick look at Zepbound and Rybelsus
Side by side: Zepbound and Rybelsus
| Zepbound | Rybelsus | |
|---|---|---|
| Medicine | Zepbound |  Rybelsus |
| Active ingredient | tirzepatide | semaglutide |
| Manufacturer | Eli Lilly | Novo Nordisk |
| How it is taken | Weekly injection | Daily tablet |
| Approved for | Weight loss and sleep apnea | Type 2 diabetes and heart risk |
| First FDA approval | 2023 | 2019 |
| Average weight loss in trials | 20.9% (SURMOUNT-1, 72 weeks) | Not listed |
| Most common side effect | Nausea 29% vs 8% on placebo | Nausea 20% vs 6% on placebo |
| List price | $499 to $1,086 per fill | $1,027.51 per 30 tablets |
| Self-pay from | $299 per month | Not listed |
| Medicare GLP-1 Bridge | $50 per month, eligible Part D | Not listed |
| FDA shortage | Resolved December 19, 2024 | Resolved February 21, 2025 |
Sources: FDA label, FDA label (DailyMed), pricinginfo.lilly.com, Novo Nordisk pricing.
Weight loss compared
No trial has compared them directly, so the results come from separate studies that used different groups and time periods.
| Trial | Who took part | Length | Group | Average weight loss | Placebo |
|---|---|---|---|---|---|
| SURMOUNT-1 | Adults with obesity or overweight, without diabetes | 72 weeks | Tirzepatide 5 mg weekly | 15% | 3.1% |
| SURMOUNT-1 | Adults with obesity or overweight, without diabetes | 72 weeks | Tirzepatide 10 mg weekly | 19.5% | 3.1% |
| SURMOUNT-1 | Adults with obesity or overweight, without diabetes | 72 weeks | Tirzepatide 15 mg weekly | 20.9% | 3.1% |
| SURMOUNT-2 | Adults with obesity or overweight who have type 2 diabetes | 72 weeks | Tirzepatide 10 mg weekly | 12.8% | 3.2% |
| SURMOUNT-2 | Adults with obesity or overweight who have type 2 diabetes | 72 weeks | Tirzepatide 15 mg weekly | 14.7% | 3.2% |
For the trials, see SURMOUNT-1 (FDA label (DailyMed)) and SURMOUNT-2 (PubMed) as sources.
Side effects compared
Compare each drug with the placebo group in that label first. Each label tested its own group of people this way.
| Side effect | Zepbound | Placebo (Zepbound trials) | Rybelsus | Placebo (Rybelsus trials) |
|---|---|---|---|---|
| Nausea | 29% | 8% | 20% | 6% |
| Diarrhea | 23% | 8% | 10% | 4% |
| Constipation | 17% | 5% | 6% | 2% |
| Vomiting | 13% | 2% | 8% | 3% |
| Abdominal Pain | 10% | 5% | 11% | 4% |
| Dyspepsia | 10% | 4% | Not listed | Not listed |
| Injection Site Reactions | 8% | 2% | Not listed | Not listed |
| Fatigue | 7% | 3% | Not listed | Not listed |
| Decreased appetite | Not listed | Not listed | 9% | 1% |
Prices and coverage compared
| Medicine | How you pay | Price |
|---|---|---|
| Zepbound | List price before insurance | $499 to $1,086 per fill |
| Zepbound | Zepbound Savings Program (insured) | from $25 for up to a 3-month fill |
| Zepbound | Commercial plan that does not cover it | $299 per month |
| Zepbound | Self-pay: LillyDirect vial or KwikPen 2.5 mg | $299 per month |
| Zepbound | Self-pay: LillyDirect vial or KwikPen 5 mg | $399 per month |
| Zepbound | For a refill within 45 days, the self-pay option through LillyDirect for 7.5 mg up to 15 mg doses applies | $449 per month |
| Zepbound | Without a refill within 45 days, the regular self-pay price applies | the monthly cost is $499 for $7.5 mg, or $699 for $10 to $15 mg per month |
| Zepbound | Self-pay via TrumpRx | $299 per month |
| Zepbound | Medicare GLP-1 Bridge (Zepbound KwikPen, eligible Part D) | $50 per month |
| Rybelsus | List price before insurance | $1,027.51 per 30 tablets |
| Rybelsus | RYBELSUS Savings Offer (insured) | starting at $25 for 1-, 2- or 3-month fills |
Prices checked November 2026 (7)
rybelsus.com, Eli Lilly, TrumpRx, CMS, Novo Nordisk pricing, pricinginfo.lilly.com, zepbound.lilly.com
Who should pick which?
- Needle-free option: Rybelsus is taken as a tablet, and Zepbound is a weekly injection.
- Without diabetes, only Zepbound is approved for weight loss.
- Only Rybelsus is approved for type 2 diabetes.
- Zepbound is approved to treat sleep apnea.
- To lower the risk of stroke and heart attack, Rybelsus is approved.
- The Medicare GLP-1 Bridge list includes Zepbound.
- If you pay cash for Zepbound, you pay $299 per month at the published self-pay rate.
Whether you switch between them is decided by your prescriber after they consider your health history, other medicines, and coverage.