Semaglutide vs tirzepatide: in the only head-to-head obesity trial, tirzepatide (Zepbound, Mounjaro) produced more weight loss than semaglutide (Wegovy, Ozempic): 20.2% versus 13.7% of body weight over 72 weeks.[1] It also lowered blood sugar more in type 2 diabetes.[2] Semaglutide has the longer list of approved uses, including heart, kidney and liver indications.[5][6] Side effects are similar for both.[17]
For full details on each drug, see our semaglutide profile and tirzepatide profile. For dosing and results, see the semaglutide dosage chart, semaglutide weight loss results and how Wegovy vs Ozempic differ.
At a glance
| Semaglutide | Tirzepatide | |
|---|---|---|
| Brands | Ozempic, Wegovy (injection and pill)[5][6] | Mounjaro, Zepbound[7][8] |
| How it works | GLP-1 receptor agonist[6] | GIP and GLP-1 receptor agonist[8] |
| Dosing | Once weekly (Wegovy pill: daily)[6] | Once weekly[8] |
| Half-life | About 1 week[6] | About 5 days[7] |
| Top weight-loss dose | 2.4 mg, up to 7.2 mg (Wegovy)[6] | 15 mg (Zepbound)[8] |
| Head-to-head weight loss | −13.7%[1] | −20.2%[1] |
Head-to-head results
Weight loss: SURMOUNT-5
SURMOUNT-5 randomized 751 adults with obesity, without diabetes, to the highest tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks.[1] The main goal was percent weight change at week 72. Key secondary goals were the share of people losing at least 10%, 15%, 20% and 25% of their weight, and the change in waist size.[1]
- Weight: −20.2% with tirzepatide versus −13.7% with semaglutide.[1]
- Waist: −18.4 cm versus −13.0 cm.[1]
- Weight-loss targets: tirzepatide outperformed semaglutide at every threshold measured.[1]
- Side effects timing: stomach and bowel side effects were the most common in both groups, mostly mild to moderate, and happened mainly while doses were being increased.[1]
- Japan: in a subgroup of 383 people meeting Japanese obesity criteria, results were similar (−20.1% vs −12.9%).[18]
Type 2 diabetes: SURPASS-2
SURPASS-2 compared tirzepatide 5, 10 and 15 mg with semaglutide 1 mg in 1,879 adults with type 2 diabetes over 40 weeks.[2]
| Tirzepatide 5 mg | 10 mg | 15 mg | Semaglutide 1 mg | |
|---|---|---|---|---|
| HbA1c change | −2.01 | −2.24 | −2.30 | −1.86 |
| Extra weight loss vs semaglutide | −1.9 kg | −3.6 kg | −5.5 kg | — |
Every tirzepatide dose was superior to semaglutide 1 mg on HbA1c.[2] Ozempic is now approved up to 2 mg, which SURPASS-2 did not test.[5]
Placebo-controlled trials compared
| Trial | Drug and dose | Weeks | Weight change | Placebo |
|---|---|---|---|---|
| STEP 1 | Semaglutide 2.4 mg | 68 | −14.9% | −2.4%[3] |
| STEP UP | Semaglutide 7.2 mg | 72 | −18.7% | −3.9%[12] |
| SURMOUNT-1 | Tirzepatide 15 mg | 72 | −20.9% | −3.1%[4] |
| STEP 6 (Japan, Korea) | Semaglutide 2.4 mg | 68 | −13.2% | −2.1%[20] |
| SURMOUNT-CN (China) | Tirzepatide 15 mg | 52 | −17.5% | −2.3%[19] |
Comparisons across separate trials are less reliable than head-to-head results, because populations and designs differ.
Side effects compared
In SURMOUNT-5, side effects were broadly similar:[17]
| Side effect | Tirzepatide | Semaglutide |
|---|---|---|
| Nausea | 43.6% | 44.4% |
| Constipation | 27.0% | 28.5% |
| Diarrhea | 23.5% | 23.4% |
| Vomiting | 15.0% | 21.3% |
| Injection-site reaction | 8.6% | 0.3% |
| Serious adverse events | 4.8% | 3.5% |
- Boxed warning: all four brands carry a warning about thyroid C-cell tumors seen in rodents, and none should be used by people with a personal or family history of medullary thyroid cancer or MEN 2.[5][6][7][8]
- Higher semaglutide dose: at 7.2 mg, abnormal skin sensations (dysesthesia) affected 22.9% versus 6.0% on 2.4 mg.[12]
- Stopping treatment: on the labels, 6.8% stopped Wegovy 2.4 mg for side effects versus 3.2% on placebo,[6] and 4.8% to 6.7% stopped Zepbound versus 3.4%.[8]
Gallbladder, pancreas and other label warnings
Both drug labels warn about the same less common problems.[6][8]
| Label finding (weight-loss trials) | Wegovy injection | Placebo | Zepbound | Placebo |
|---|---|---|---|---|
| Gallstones (cholelithiasis) | 1.6% | 0.7% | 1.1% | 1.0% |
| Gallbladder inflammation (cholecystitis) | 0.6% | 0.2% | 0.7% | 0.2% |
- Pancreatitis: confirmed acute pancreatitis was rare in the weight-loss trials of both drugs, and both labels say to stop the drug if it is suspected.[6][8]
- Heart rate: Wegovy raised resting heart rate by 1 to 4 beats per minute on average versus placebo.[6]
- Low blood sugar: the risk rises when either drug is combined with insulin or a sulfonylurea.[6][8]
- Surgery: both labels note food aspiration under anesthesia or deep sedation with GLP-1 drugs, so tell your care team before any procedure.[6][8]
- Birth control pills: Zepbound may make them less effective. Its label advises a non-oral method, or adding a barrier method, for 4 weeks after starting and after each dose increase.[8]
- Pregnancy: the Wegovy label says to stop at least 2 months before a planned pregnancy because semaglutide stays in the body a long time.[6] The Zepbound label says to stop once pregnancy is recognized.[8]
Heart, kidney and other approved uses
| Use | Semaglutide | Tirzepatide |
|---|---|---|
| Type 2 diabetes | Ozempic[5] | Mounjaro (adults and children 10+)[7] |
| Weight management | Wegovy (adults and teens 12+)[6] | Zepbound (adults)[8] |
| Heart attack and stroke risk | Ozempic and Wegovy[5][6] | Mounjaro, in type 2 diabetes[7] |
| Kidney disease in type 2 diabetes | Ozempic[5] | Not approved |
| MASH liver disease | Wegovy[6] | Not approved |
| Obstructive sleep apnea | Not approved | Zepbound[8] |
- SELECT: in 17,604 adults with heart disease and obesity, semaglutide cut heart attack, stroke or cardiovascular death from 8.0% to 6.5%.[9]
- SURPASS-CVOT: in 13,165 people with type 2 diabetes and heart disease, tirzepatide was non-inferior to dulaglutide (12.2% vs 13.1%), not superior.[10]
- Kidneys (FLOW): semaglutide lowered major kidney events by 24%.[11]
- Liver (ESSENCE): semaglutide resolved MASH in 62.9% versus 34.3%.[14]
- Sleep apnea: tirzepatide is the only one of the two approved for it.[13]
- Heart failure with preserved ejection fraction: both improved symptoms in trials,[15][16] but neither label includes this use.
Dosing compared
| Starting dose | Steps | Maximum | |
|---|---|---|---|
| Ozempic | 0.25 mg weekly | Every 4+ weeks to 0.5, 1, 2 mg | 2 mg[5] |
| Wegovy injection | 0.25 mg weekly | Monthly to 0.5, 1, 1.7, 2.4 mg | 7.2 mg[6] |
| Wegovy pill | 1.5 mg daily | Monthly to 4, 9, 25 mg | 25 mg[6] |
| Mounjaro | 2.5 mg weekly | +2.5 mg every 4+ weeks | 15 mg (10 mg in children)[7] |
| Zepbound | 2.5 mg weekly | +2.5 mg every 4+ weeks | 15 mg[8] |
Missed doses
- Wegovy injection: if the next dose is more than 2 days away, take the missed dose as soon as possible; if it is less than 2 days away, skip it. If 2 or more doses in a row are missed, restart at a lower dose.[6]
- Zepbound: take a missed dose within 4 days. After that, skip it and take the next dose on the usual day.[8]
Switching from semaglutide to tirzepatide
There is no official dose conversion between semaglutide and tirzepatide. Neither label gives one, and both say not to combine them with other GLP-1 drugs.[6][8] The only published switching estimates come from a Lilly modeling study, not a clinical trial.[21] The only official switching instructions are between Wegovy injection and Wegovy pills.[6] Any switch should be planned with a prescriber.
Compounded versions
FDA has declared the semaglutide and tirzepatide shortages over. As of May 31, 2026, it had received 990 adverse event reports linked to compounded semaglutide and more than 730 linked to compounded tirzepatide, and it says such events are likely underreported.[22] Some reports involved dosing errors, when patients or professionals measured or calculated the wrong dose.[22] FDA also says salt forms such as semaglutide sodium are different active ingredients from the approved drug.[22] For mixing and measuring vials safely, see our guide to reconstituting peptides.
Questions to ask a clinician
- Which drug fits my goals and conditions, such as heart disease, sleep apnea or type 2 diabetes?
- Which does my insurance cover, and what would I pay?
- How will we handle side effects while my dose goes up?
- If I switch, what starting dose will I use, and when?
- Do I need to change other medicines or birth control?
