Tirzepatide vs Rybelsus: Weight Loss, Side Effects, Price
Tirzepatide and Rybelsus (semaglutide) are both GLP-1 medicines, weekly injection versus daily tablet. Tirzepatide self-pay starts at $299 per month.
A quick look at Zepbound and Rybelsus
Tirzepatide and Rybelsus, side by side
| Tirzepatide | Rybelsus | |
|---|---|---|
| Medicine | tirzepatide |  Rybelsus |
| Active ingredient | tirzepatide | semaglutide |
| Manufacturer | Eli Lilly | Novo Nordisk |
| How it is taken | Weekly injection | Daily tablet |
| Approved for | Heart risk, weight loss, sleep apnea, plus Type 2 diabetes | Type 2 diabetes and heart risk |
| First FDA approval | 2022 | 2019 |
| Average weight loss in trials | 20.9% (SURMOUNT-1, 72 weeks) | Not listed |
| Most common side effect | Nausea 18% vs 4% on placebo | Nausea 20% vs 6% on placebo |
| List price | $1,112.16 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
Direct comparisons have not been made in any trial. The results come from separate trials that used different participants and lasted different lengths.
| Trial | Who took part | Length | Group | Average weight loss | Placebo | A1C change |
|---|---|---|---|---|---|---|
| SURMOUNT-1 | Adults with obesity or overweight, without diabetes | 72 weeks | Tirzepatide 5 mg weekly | 15% | 3.1% | Not listed |
| SURMOUNT-1 | Adults with obesity or overweight, without diabetes | 72 weeks | Tirzepatide 10 mg weekly | 19.5% | 3.1% | Not listed |
| SURMOUNT-1 | Adults with obesity or overweight, without diabetes | 72 weeks | Tirzepatide 15 mg weekly | 20.9% | 3.1% | Not listed |
| SURMOUNT-2 | Adults who have type 2 diabetes and are obese or overweight | 72 weeks | Tirzepatide 10 mg weekly | 12.8% | 3.2% | Not listed |
| SURMOUNT-2 | Adults who have type 2 diabetes and are obese or overweight | 72 weeks | Tirzepatide 15 mg weekly | 14.7% | 3.2% | Not listed |
| SURPASS-1 | Adults with type 2 diabetes who rely only on diet and exercise | 40 weeks | Tirzepatide 5 mg weekly | Not listed | Not listed | -1.87 percentage points (mean HbA1c change) |
| SURPASS-1 | Adults with type 2 diabetes who rely only on diet and exercise | 40 weeks | Tirzepatide 10 mg weekly | Not listed | Not listed | -1.89 percentage points (mean HbA1c change) |
| SURPASS-1 | Adults with type 2 diabetes who rely only on diet and exercise | 40 weeks | Tirzepatide 15 mg weekly | Not listed | Not listed | -2.07 percentage points (mean HbA1c change) |
Trial sources: SURMOUNT-1 (FDA label (DailyMed)), SURMOUNT-2 (PubMed), SURPASS-1 (PubMed).
Side effects compared
Every label ran its own trial with its own placebo group. Compare each drug against the placebo from its own trial first.
| Side effect | Mounjaro | Placebo (Mounjaro trials) | Rybelsus | Placebo (Rybelsus trials) |
|---|---|---|---|---|
| Nausea | 18% | 4% | 20% | 6% |
| Diarrhea | 17% | 9% | 10% | 4% |
| Decreased Appetite | 11% | 1% | 9% | 1% |
| Vomiting | 9% | 2% | 8% | 3% |
| Dyspepsia | 8% | 3% | Not listed | Not listed |
| Constipation | 7% | 1% | 6% | 2% |
| Abdominal Pain | 6% | 4% | 11% | 4% |
Price and coverage compared
| Medicine | How you pay | Price |
|---|---|---|
 Mounjaro | List price before insurance | $1,112.16 per fill |
| Mounjaro | Mounjaro Savings Card (insured) | from $25 for up to a 3-month fill |
| Mounjaro | Commercial plan that does not cover it | $499 per month |
 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 | Self-pay: LillyDirect vial or KwikPen 2.5 mg | $299 per month |
| Zepbound | Commercial plan that does not cover it | $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) | for 1, 2, or 3 months, a fill starts at $25 |
Prices checked November 2026 (8)
pricinginfo.lilly.com 1 2, mounjaro.lilly.com, zepbound.lilly.com, Eli Lilly, CMS, Novo Nordisk prices, rybelsus.com.
Who should pick which?
- No needles are needed because Rybelsus is taken as a tablet; Tirzepatide is given by a weekly injection.
- Tirzepatide is the only option approved for weight loss without diabetes.
- Tirzepatide is approved to treat sleep apnea.
- Under 18: Tirzepatide is approved for some children.
- Tirzepatide appears on the Medicare GLP-1 Bridge list.
- If you pay cash, Tirzepatide's published self-pay cost is $299 per month.
Your prescriber weighs your health history, the other medicines you take, and your coverage.