SharpySemaglutide vs Tirzepatide: Weight Loss, Side Effects, Cost
Tirzepatide (Zepbound, Mounjaro) causes more weight loss than semaglutide (Wegovy, Ozempic). In SURMOUNT-5, the only head-to-head obesity trial, people lost 20.2% of their body weight on tirzepatide vs 13.7% on semaglutide over 72 weeks. Both cause similar stomach side effects, semaglutide has a proven heart-attack and stroke benefit for weight loss patients, and self-pay prices are close ($349 for most Wegovy doses, $299 to $449 for Zepbound). Whichever your prescriber picks, Sharpy gives you one protein target and one 20-minute workout a day so more of the loss is fat, not muscle.
Semaglutide or tirzepatide: which one works better, and is the difference worth caring about? Tirzepatide leads to more weight loss. In the one trial that tested them head to head for obesity, people lost about 20% of their weight on tirzepatide and about 14% on semaglutide. Semaglutide still has real strengths, like a proven heart benefit and a pill version. Side effects and self-pay prices are close. Here is the full picture, using the FDA labels and the two head-to-head trials.
What is semaglutide vs tirzepatide? Brand names and how they work
These are the active ingredients. The brand name tells you what the drug is approved for.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Maker | Novo Nordisk | Eli Lilly |
| How it works | GLP-1 receptor only | GIP and GLP-1 receptors |
| Weight-loss brand | Wegovy (shot and pill) | Zepbound (pen and vials) |
| Diabetes brands | Ozempic (shot and pill), Rybelsus | Mounjaro |
| How often (shot) | Once a week | Once a week |
| Weight-loss doses | 0.25 mg up to 2.4 mg, plus Wegovy HD 7.2 mg | 2.5 mg up to 15 mg |
| Other approved uses (weight-loss brand) | Lower heart attack and stroke risk in adults with heart disease and obesity or overweight | Moderate to severe sleep apnea in adults with obesity |
| Teens | Wegovy shot approved from age 12 | Not approved under 18 |
Tirzepatide's second target, GIP, is the main reason people expect it to work better. Our guide to GLP-1 vs GIP explains the two hormones in plain English.
Semaglutide vs tirzepatide weight loss: the SURMOUNT-5 results
SURMOUNT-5 was the first trial to test the two weight-loss doses against each other. It ran 72 weeks in 751 adults with obesity and no type 2 diabetes. It was published in the New England Journal of Medicine in May 2025 and paid for by Eli Lilly. It was open-label, which means people knew which drug they got. Each person used the highest dose they could tolerate: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg.
| Result at 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Average weight loss | -20.2% | -13.7% |
| Lost 20% or more of body weight | 48.4% | 27.3% |
| Waist size change | -18.4 cm (about 7.2 in) | -13.0 cm (about 5.1 in) |
| Quit because of stomach side effects | 2.7% | 5.6% |
The gap was 6.5 percentage points. For a 220-pound person, that is roughly 44 pounds on tirzepatide vs 30 pounds on semaglutide, if they match the average. Many people land above or below that average.
For how both stack up against Lilly's next drug, see retatrutide vs semaglutide vs tirzepatide. SURMOUNT-5 did not test Wegovy HD 7.2 mg, which came later. No trial has compared Wegovy HD with Zepbound. For the label numbers and Lilly's indirect comparison, see Wegovy HD vs Zepbound.
Semaglutide vs tirzepatide for diabetes: the SURPASS-2 results
For type 2 diabetes, the head-to-head was SURPASS-2, published in NEJM in 2021. It ran 40 weeks in 1,879 adults on metformin. It compared three Mounjaro doses with Ozempic 1 mg, not the higher Ozempic 2 mg dose.
| Dose | A1C drop | Weight change |
|---|---|---|
| Tirzepatide 5 mg | -2.01 points | -7.6 kg |
| Tirzepatide 10 mg | -2.24 points | -9.3 kg |
| Tirzepatide 15 mg | -2.30 points | -11.2 kg |
| Semaglutide 1 mg | -1.86 points | -5.7 kg |
Every tirzepatide dose beat semaglutide 1 mg on both A1C and weight. In this trial, slightly more people stopped tirzepatide because of side effects (6.0% to 8.5% vs 4.1%). If you have diabetes, our Trulicity vs Ozempic guide covers another common comparison.
Semaglutide vs tirzepatide side effects
The common side effects are the same kind for both: mostly stomach and bowel. These rates come from each weight-loss label. They come from different trials, so compare them loosely.
| Side effect | Wegovy 2.4 mg | Placebo (Wegovy trials) | Zepbound 5 / 10 / 15 mg | Placebo (Zepbound trials) |
|---|---|---|---|---|
| Nausea | 44% | 16% | 25% / 29% / 28% | 8% |
| Diarrhea | 30% | 16% | 19% / 21% / 23% | 8% |
| Vomiting | 24% | 6% | 8% / 11% / 13% | 2% |
| Constipation | 24% | 11% | 17% / 14% / 11% | 5% |
| Stopped due to side effects | 6.8% | 3.2% | 4.8% / 6.3% / 6.7% | 3.4% |
Both labels carry the same boxed warning about thyroid C-cell tumors in rodents. Neither drug should be used if you or your family have had medullary thyroid cancer or MEN 2. Both list warnings for pancreatitis, gallbladder problems, low blood sugar with insulin or sulfonylureas, and kidney injury from dehydration. For day-to-day relief, see our guide to managing nausea on GLP-1 drugs.
Semaglutide vs tirzepatide and muscle loss
Neither drug only burns fat. In the body-scan part of STEP 1, about 39% to 40% of the tissue lost on semaglutide 2.4 mg was lean mass. In SURMOUNT-1, about 25% of the loss on tirzepatide was lean mass. Those are different trials with different methods, so do not read them as a clear win for tirzepatide. What both show is that bigger, faster loss puts muscle at risk unless you push back.
The two habits that help most are eating enough protein and lifting a few times a week. Sharpy sets one daily protein target, gives you one 20-minute workout, and tracks a Shape Score so you can see whether the weight coming off is fat. Our guide to sarcopenia on GLP-1 drugs goes deeper.
Semaglutide vs tirzepatide cost
| How you pay | Semaglutide (Wegovy) | Tirzepatide (Zepbound) |
|---|---|---|
| Self-pay pen | $349 a month (0.25 to 2.4 mg), $399 for Wegovy HD 7.2 mg, $199 for the first two starter fills through Dec 31, 2026 | KwikPen or vials: $299 (2.5 mg), $399 (5 mg), $449 (7.5 to 15 mg) if refilled within 45 days |
| Self-pay pill | Wegovy pill $149 to $299 a month | No tirzepatide pill |
| Where | NovoCare Pharmacy | LillyDirect |
| Commercial insurance | Depends on your plan's obesity coverage | Depends on your plan's obesity coverage |
Prices come from NovoCare and LillyDirect, read October 28 and 29, 2026. Our guides to NovoCare Pharmacy and Zepbound vials list every dose and condition. Compounded versions of both drugs are sold online. They are not FDA-approved, and we do not recommend them.
Semaglutide vs tirzepatide: which is better for you?
Your prescriber makes this call. These questions usually decide it:
- Is the most weight loss the top goal? Tirzepatide did better head to head.
- Do you have heart disease? Wegovy is approved to lower heart attack and stroke risk in that group.
- Do you have sleep apnea? Zepbound is approved to treat it.
- Would you rather take a pill? Semaglutide comes as the Wegovy pill. There is no tirzepatide pill, as our Mounjaro pill guide explains.
- Is it for a teen? Only Wegovy is approved from age 12.
- What does your plan cover? This often decides it first.
Newer drugs are coming too. Retatrutide, a three-hormone drug from Lilly, is still in trials. Our retatrutide vs Ozempic guide covers its latest results. Do not switch, stop or combine these drugs on your own.
The bottom line
Tirzepatide beats semaglutide on weight loss and on A1C in the two head-to-head trials. Semaglutide answers back with a proven heart benefit, a pill option and approval for teens. Side effects and self-pay prices are close enough that coverage and your health history usually decide. On either drug, protect your muscle. Sharpy gives you one protein target, one 20-minute workout and one Shape Score a day, so you can see that the loss is fat, not muscle.
Sources
- Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5), NEJM 2025
- ACC Journal Scan: SURMOUNT-5
- Healio: Tirzepatide bests semaglutide for weight loss in adults with obesity
- Frías JP et al. Tirzepatide versus semaglutide once weekly in type 2 diabetes (SURPASS-2), NEJM 2021 (ACC summary)
- Zepbound (tirzepatide) prescribing information, August 2026 (openFDA)
- Wegovy (semaglutide) prescribing information (openFDA)
- NovoCare Pharmacy self-pay prices
- LillyDirect: Zepbound self-pay
Questions people ask
Semaglutide vs tirzepatide: which is better for weight loss?
Tirzepatide. In SURMOUNT-5, a 72-week trial of 751 adults with obesity and no diabetes, average weight loss was 20.2% on tirzepatide vs 13.7% on semaglutide. About 48% of the tirzepatide group lost at least 20% of their weight, vs about 27% on semaglutide.
What is the difference between semaglutide and tirzepatide?
Semaglutide acts on one gut hormone receptor, GLP-1. Tirzepatide acts on two, GIP and GLP-1. Semaglutide is made by Novo Nordisk and sold as Wegovy, Ozempic and Rybelsus. Tirzepatide is made by Eli Lilly and sold as Zepbound and Mounjaro.
Semaglutide vs tirzepatide: which is safer?
Both carry the same boxed warning about thyroid C-cell tumors in rodents and the same main warnings (pancreatitis, gallbladder problems, kidney injury from dehydration). Neither trial showed a clear safety winner. Semaglutide has a longer track record and a proven heart benefit in people with obesity and heart disease. Your prescriber weighs this for you.
Does tirzepatide have fewer side effects than semaglutide?
Rates look similar, though the drugs were tested in different trials for their labels. On the Zepbound label, nausea hit 25% to 29% of people vs 8% on placebo. On the Wegovy label, nausea hit 44% vs 16% on placebo. In SURMOUNT-5, more people quit semaglutide because of stomach side effects (5.6%) than tirzepatide (2.7%).
Semaglutide vs tirzepatide: which is cheaper?
Self-pay prices are close. As of late October 2026, NovoCare lists most Wegovy pen doses at $349 a month, and LillyDirect lists Zepbound at $299 (2.5 mg), $399 (5 mg) and $449 (7.5 mg to 15 mg, refilled within 45 days). With insurance, your plan decides, and many plans cover one but not the other.
Can you switch from semaglutide to tirzepatide?
Yes, people do switch, but there is no official conversion chart in either label. Your prescriber picks the new starting dose. Never take both at once: both labels say not to combine them with other GLP-1 drugs.