What Is the Difference Between Semaglutide and Tirzepatide?
Semaglutide copies one gut hormone, GLP-1. Tirzepatide copies two, GLP-1 and GIP. Both hormones are released after you eat and help control appetite and blood sugar. Activating both is the reason tirzepatide is often called a “dual agonist.”
The brand names can be confusing, because each drug is sold twice:
| Semaglutide (Novo Nordisk) | Tirzepatide (Eli Lilly) | |
|---|---|---|
| For weight loss | Wegovy: weekly pen, daily pill, Wegovy HD 7.2 mg | Zepbound: weekly vial, KwikPen or single-dose pen |
| For type 2 diabetes | Ozempic (pen) | Mounjaro (pen) |
| Other approved uses | Wegovy: lowering heart risk in adults with heart disease and excess weight | Zepbound: obstructive sleep apnea in adults with obesity |
| How it works | GLP-1 receptor agonist | GIP and GLP-1 receptor agonist |
| Pill version | Yes (Wegovy pill) | No; Lilly’s pill, Foundayo, is a different drug (orforglipron) |
Ozempic and Wegovy contain the same active ingredient, and so do Mounjaro and Zepbound. The diabetes versions aren’t approved for weight loss, which matters for insurance and for the price you pay.
Which Causes More Weight Loss, Semaglutide or Tirzepatide?
Tirzepatide caused more weight loss in the trials. The clearest evidence is SURMOUNT-5, published in the New England Journal of Medicine in 2025. It randomly assigned 751 adults with obesity, but without type 2 diabetes, to the highest dose they could tolerate of either drug for 72 weeks.
Average weight loss was 20.2% on tirzepatide and 13.7% on semaglutide. Waist size dropped by 18.4 cm against 13.0 cm. People on tirzepatide were also more likely to reach the 10%, 15%, 20% and 25% loss marks. Eli Lilly, which makes tirzepatide, funded the trial, and it was open-label, so participants knew which drug they got.
The earlier placebo-controlled trials point the same way, though they weren’t a direct comparison:
| Trial | Drug and dose | Length | Weight loss on drug | On placebo |
|---|---|---|---|---|
| STEP 1 | Semaglutide 2.4 mg | 68 weeks | 14.9% | 2.4% |
| SURMOUNT-1 | Tirzepatide 5 mg | 72 weeks | 15.0% | 3.1% |
| SURMOUNT-1 | Tirzepatide 10 mg | 72 weeks | 19.5% | 3.1% |
| SURMOUNT-1 | Tirzepatide 15 mg | 72 weeks | 20.9% | 3.1% |
| SURMOUNT-5 (head-to-head) | Tirzepatide 10–15 mg vs semaglutide 1.7–2.4 mg | 72 weeks | 20.2% vs 13.7% | No placebo |
Sources: STEP 1 and SURMOUNT-1 figures as summarized in the 2025 joint nutrition advisory (Table 1); SURMOUNT-5 from the NEJM abstract.
These are averages. The same advisory notes that individual results vary widely: some people lose very little, and others lose 30% or more.
How Much Do Semaglutide and Tirzepatide Cost?
Semaglutide is cheaper at the makers’ own cash prices. We rechecked these on November 4, 2026:
| Wegovy (semaglutide) | Zepbound (tirzepatide) | |
|---|---|---|
| Starting doses | $199 for the first two fills (new patients, through Dec 31, 2026) | $299 at 2.5 mg |
| Next dose | $349 | $399 at 5 mg |
| Maintenance | $349 (up to 2.4 mg); $399 for Wegovy HD 7.2 mg | $449 at 7.5–15 mg, if you refill within 45 days |
| Pill option | Wegovy pill: $149 / $199 / $299 by dose | None (Foundayo is a different drug) |
| Where | NovoCare, local pharmacies, TrumpRx coupon | LillyDirect, Walmart pickup, retail with Lilly’s card |
| First year, cash | About $4,237 (2 × $199 + 11 × $349) | About $5,637 (up to 10–15 mg) |
At maintenance, Zepbound costs about $100 a month more than a Wegovy pen, or $1,200 a year. The first-year totals assume 13 fills of 28 days, as in our GLP-1 cost without insurance guide. Several of these offers end December 31, 2026.
Compounded versions cost less but aren’t FDA-approved. In our November 2026 GLP-1 Price Index, the median month-to-month price was $189 for compounded semaglutide (16 providers) and $249 for compounded tirzepatide (15 providers).
Which Has More Side Effects?
They’re similar. In SURMOUNT-5, the most common side effects in both groups were gastrointestinal, mostly mild to moderate, and they happened mainly while the dose was being raised.
The usual ones for both drugs are nausea, diarrhea, vomiting and constipation. Both labels carry the same boxed warning about thyroid C-cell tumors seen in rodents. Neither drug should be used by anyone with a personal or family history of medullary thyroid cancer or MEN 2. Both also list warnings for pancreatitis, gallbladder problems and dehydration.
Because the GI effects peak during dose increases, both drugs start low and step up over months. How you tolerate the steps can matter as much as the trial averages. Some people switch from one drug to the other for that reason, which is a decision for your prescriber.
Ask about the warning signs
Severe stomach pain that won’t go away, pain spreading to your back, or vomiting you can’t stop can signal pancreatitis or a gallbladder problem. Get medical help. Our side effects guide lists the warning signs from both FDA labels.
How Are the Doses Different?
Both are once-weekly shots that start low and climb every four weeks, per their FDA labels. Your prescriber decides your doses.
- Wegovy (semaglutide): 0.25 mg, then 0.5, 1 and 1.7 mg, reaching the 2.4 mg maintenance dose in week 17. Wegovy HD adds a 7.2 mg dose. The pill follows its own schedule, from 1.5 mg up to 25 mg.
- Zepbound (tirzepatide): 2.5 mg for four weeks, then 5 mg, rising in 2.5 mg steps if needed. Maintenance doses are 5, 10 or 15 mg.
That price structure matters for your budget. Wegovy’s price is flat at $349 for most doses. Zepbound’s rises with the dose, from $299 to $449, and its top price holds only if you refill within 45 days.
Which Is Better for You?
There’s no single winner. It depends on your goals, your health and your coverage. What the evidence and prices say:
- For the most weight loss: tirzepatide led in the head-to-head trial.
- For the lowest cash price: semaglutide, especially the Wegovy pill at $149 to $299.
- For heart disease: Wegovy is approved to lower heart attack and stroke risk in adults with heart disease and excess weight.
- For sleep apnea: Zepbound is approved for moderate-to-severe obstructive sleep apnea in adults with obesity.
- If you don’t want shots: semaglutide comes as the Wegovy pill. Lilly’s pill, Foundayo, is a different drug.
- If you have insurance: the drug your plan covers usually decides, since coverage can turn a $349 to $449 cash price into a copay.
Ask your prescriber which fits your history, including any other conditions and medicines. This guide can’t make that call for you.
Compare Prices for Both Drugs
Can You Switch From Semaglutide to Tirzepatide?
Yes, people do switch, but only with your prescriber’s guidance. Neither label gives a direct switching chart, so your prescriber usually picks a starting dose of the new drug based on how you did on the old one. The Wegovy and Zepbound labels both advise against using them with other GLP-1 medicines, so you don’t take both at once.
Common reasons people switch are side effects, cost, a supply problem or insurance coverage. Price matters here too. Moving from a $349 Wegovy pen to Zepbound can mean starting again at $299 for the 2.5 mg dose, then paying up to $449 a month at maintenance.
Does Medicare or Insurance Cover Them?
Coverage depends on why the drug is prescribed. Since July 1, 2026, Medicare’s temporary GLP-1 Bridge covers Wegovy (pen or pill) and the Zepbound KwikPen for weight loss at a $50 monthly copay, if you qualify. It runs through December 31, 2027.
Private insurance varies by plan and employer. Many plans cover Ozempic or Mounjaro for diabetes but not Wegovy or Zepbound for weight loss. Some cover one weight-loss drug but not the other. Ask your plan which is on its formulary before your prescriber writes the prescription.
