Semaglutide vs tirzepatide
Semaglutide vs tirzepatide: one receptor or two
Semaglutide vs tirzepatide (or tirzepatide vs semaglutide) is the question underneath Ozempic, Wegovy, Mounjaro and Zepbound. This page sets out how the two molecules work, what the head-to-head trials found for weight, blood sugar and side effects, what is known about lean mass and muscle, and what to ask your prescriber. It never recommends one over the other.
On this page
- Semaglutide vs tirzepatide at a glance
- How semaglutide and tirzepatide work
- Semaglutide vs tirzepatide for weight loss: SURMOUNT-5
- Semaglutide vs tirzepatide in type 2 diabetes: SURPASS-2
- Which GLP-1 is best for weight loss?
- Semaglutide vs tirzepatide side effects
- Muscle loss: what the lean-mass data show
- Food noise: what is and isn't known
- Doses and forms: facts, not instructions
- Switching from semaglutide to tirzepatide, or back
- Questions to bring to your prescriber
- Questions people ask
- Sources
In short
- Semaglutide (Novo Nordisk; sold as Ozempic, Wegovy and Rybelsus) activates the GLP-1 receptor, while tirzepatide (Eli Lilly; sold as Mounjaro and Zepbound) is one molecule that activates both the GIP and GLP-1 receptors.1,2,3,4,5
- In SURMOUNT-5, a 72-week head-to-head trial in 751 adults with obesity, or overweight with a weight-related condition, and without type 2 diabetes, average weight change was −13.7% on semaglutide (1.7 or 2.4 mg) and −20.2% on tirzepatide (10 or 15 mg), counting everyone randomized.6
- In SURPASS-2, a 40-week trial in 1,879 adults with type 2 diabetes, HbA1c fell by an average of 1.9 points on semaglutide 1 mg and 2.0 to 2.3 points on tirzepatide 5 to 15 mg.3,9
- Side effects were mostly digestive with both; in SURMOUNT-5, 8.0% on semaglutide and 6.1% on tirzepatide stopped because of an adverse event, in a trial not designed to compare safety.7
- No trial can say which medicine suits you: averages are one input alongside your health, your other conditions, how you'd take it and your coverage, and the choice is yours to make with your prescriber.
Semaglutide vs tirzepatide at a glance
| Semaglutide | Tirzepatide | |
|---|---|---|
| Made by | Novo Nordisk | Eli Lilly and Company |
| Receptors it activates | GLP-14 | GIP and GLP-11 |
| US brands | Ozempic (weekly injection; also daily tablets), Wegovy (weekly injection or daily pill), Rybelsus (daily tablets)2,4,5 | Mounjaro and Zepbound (weekly injections)1,3 |
| Main US approvals | Type 2 diabetes (Ozempic, Rybelsus); weight management (Wegovy); heart, kidney and MASH liver indications on some brands2,4,5 | Type 2 diabetes and heart risk (Mounjaro); weight management and obstructive sleep apnea (Zepbound)1,3 |
| Injection strengths | 0.25 to 2 mg (Ozempic); 0.25 to 7.2 mg (Wegovy)2,4 | 2.5 to 15 mg (both brands)1,3 |
| Half-life | About 1 week4 | About 5 days (5 to 6 in people with overweight or obesity)1,3 |
| Pill form | Yes: Wegovy pill for weight; Rybelsus and Ozempic tablets for diabetes2,5 | No: both brands are injections.1,3 See whether there is a Mounjaro pill. |
| SURMOUNT-5 weight change | −13.7% (1.7 or 2.4 mg)6 | −20.2% (10 or 15 mg)6 |
| SURPASS-2 HbA1c change | −1.9 points (1 mg)3 | −2.0 to −2.3 points (5 to 15 mg)3 |
| Boxed warning | Thyroid C-cell tumors seen in rodents4 | Thyroid C-cell tumors seen in rodents1 |
From the current US labels (Ozempic, Wegovy, Rybelsus and Ozempic tablets, Mounjaro, Zepbound), except the SURMOUNT-5 row, which is from the trial report: 72 weeks, adults without type 2 diabetes, counting everyone randomized. The SURPASS-2 row, from the Mounjaro label, is 40 weeks in adults with type 2 diabetes. Milligram numbers can't be compared between the two molecules. None of this is a dose to take; your prescriber sets that.
How semaglutide and tirzepatide work
Both act on receptors for hormones made in the gut. The difference is how many.
Semaglutide
GLP-1 receptor agonist
- Activates the GLP-1 receptor only.4
- Lowers blood sugar in type 2 diabetes and delays stomach emptying.4
- Lowers body weight with more fat lost than lean mass, the Wegovy label says.2
- Half-life about 1 week; the level steadies after 4 to 5 weeks of weekly doses.4
- Also made as tablets, which are taken on an empty stomach because only a small fraction is absorbed.2,5
Tirzepatide
GIP and GLP-1 receptor agonist
- One molecule that activates two receptors: GIP and GLP-1.1
- The label calls GLP-1 a regulator of appetite and calorie intake, and says nonclinical studies suggest GIP "may further contribute" to regulating food intake.1
- Lowers blood sugar, and slows stomach emptying most after the first dose.1
- Lowers body weight with more fat lost than lean mass, the Zepbound label says.1
- Half-life about 5 days; the level steadies after 4 weeks of weekly doses.3
A second receptor is a design difference, not proof on its own of a bigger effect. The head-to-head trials below are what compare the results.
Semaglutide vs tirzepatide for weight loss: SURMOUNT-5
SURMOUNT-5 is the head-to-head trial at weight-management doses, published in the New England Journal of Medicine in 2025. It randomly assigned 751 adults in the US and Puerto Rico who had obesity, or overweight with high blood pressure, abnormal blood fats, obstructive sleep apnea or heart disease, and who did not have type 2 diabetes. For 72 weeks they took the highest dose they tolerated of semaglutide (1.7 or 2.4 mg) or tirzepatide (10 or 15 mg) once a week, with diet and activity counseling in both groups.6,7
Most people reached the top dose: 92.8% on semaglutide had at least one 2.4 mg dose, and 89.3% on tirzepatide at least one 15 mg dose. The trial was open-label, so participants knew which medicine they took, and it was funded by Lilly, which makes tirzepatide.6,7
SURMOUNT-5 results at 72 weeks
| Average result | Semaglutide | Tirzepatide |
|---|---|---|
| Change in body weight6 | −13.7% | −20.2% |
| Weight lost7 | 15.0 kg (33.1 lb) | 22.8 kg (50.3 lb) |
| Change in waist size6 | −13.0 cm | −18.4 cm |
| Lost at least 10%7 | 60.5% | 81.6% |
| Lost at least 15%7 | 40.1% | 64.6% |
| Lost at least 20%7 | 27.3% | 48.4% |
| Lost at least 25%7 | 16.1% | 31.6% |
Treatment-regimen estimand: everyone randomized is counted, whether or not they kept taking the medicine. The weight and waist differences were statistically significant (P<0.001).6 The ClinicalTrials.gov record gives higher milestone figures because it counts only people with week-72 data; the two sets shouldn't be mixed.8
In plain terms, people lost about a seventh of their body weight on average on semaglutide and about a fifth on tirzepatide. Lilly's headline of a "47% greater relative weight loss" is the ratio of those two averages, not a 47-point gap.7
Four limits matter. The trial was open-label. It didn't include people with type 2 diabetes. It compared weekly injections, not the pills or Wegovy's newer 7.2 mg dose.2 And it wasn't designed to compare safety.7 For how this plays out brand by brand, see Zepbound vs Wegovy.
Semaglutide vs tirzepatide in type 2 diabetes: SURPASS-2
SURPASS-2, an open-label trial funded by Lilly, randomly assigned 1,879 adults with type 2 diabetes who were taking metformin to semaglutide 1 mg or tirzepatide 5, 10 or 15 mg, once a week for 40 weeks.9 On average, HbA1c fell by 1.9 points on semaglutide and by 2.0, 2.2 and 2.3 points on the three tirzepatide doses; weight fell by 5.7 kg against 7.6, 9.3 and 11.2 kg; and 79% on semaglutide reached an HbA1c below 7%, against 82% to 86% on tirzepatide.3
Nausea affected 18% on semaglutide and 17% to 22% on tirzepatide, with similar rates of diarrhea and vomiting.9 The comparison was with semaglutide 1 mg, so it doesn't cover the 2 mg diabetes strength or weight-management doses.4 The brand-level view is in Mounjaro vs Ozempic.
Which GLP-1 is best for weight loss?
There's no single best GLP-1 for everyone, and no trial can tell you which will suit you. Trials tell you how groups of people did on average. Between these two, the only head-to-head trial at weight-management doses is SURMOUNT-5: −20.2% on tirzepatide (10 or 15 mg) and −13.7% on semaglutide (1.7 or 2.4 mg) over 72 weeks, in adults without type 2 diabetes, counting everyone randomized.6
Each medicine's own placebo-controlled trials can't be ranked against each other, because they enrolled different people for different lengths of time. For every option side by side, including newer daily pills, see our guide to GLP-1 medications and Foundayo vs Zepbound.
What else goes into the choice
- What it's for. Type 2 diabetes, weight, sleep apnea, or heart, kidney or liver risk each point to particular brands.1,2,3,4
- How you'd take it. Semaglutide also comes as a daily pill with an empty-stomach routine; tirzepatide is a weekly injection.1,2
- Your history. Both carry the same boxed warning and similar warnings, and your prescriber knows what applies to you.1,2
- Cost and coverage. These change often and differ by plan and country, so check with your insurer or pharmacy.
Semaglutide vs tirzepatide side effects
Both cause mostly digestive side effects, reported most often while the dose is being stepped up.1,2 In SURMOUNT-5, nausea, diarrhea and constipation were about as common with either. Vomiting and reflux were less common with tirzepatide, and injection-site reactions, belching and hair loss more common.8
Adverse events in SURMOUNT-5
| Reported during the trial | Semaglutide (376 people) | Tirzepatide (374 people) |
|---|---|---|
| Nausea | 44.4% | 43.6% |
| Constipation | 28.5% | 27.0% |
| Diarrhea | 23.4% | 23.5% |
| Vomiting | 21.3% | 15.0% |
| Fatigue | 12.2% | 10.4% |
| Reflux (GERD) | 10.6% | 6.1% |
| Belching | 7.7% | 9.9% |
| Injection-site reaction | 0.3% | 8.6% |
| Hair loss | 6.1% | 8.3% |
| Serious adverse event | 3.5% | 4.8% |
| Stopped because of an adverse event | 8.0% | 6.1% |
Common non-serious and all serious adverse events from the ClinicalTrials.gov results; there were no deaths.8 Discontinuation as reported by Lilly, which notes the trial was not designed to compare safety.7
What each label's weight-management trials found
Each label's own tables come from different trials, populations and lengths, and the labels say rates can't be directly compared between medicines. Placebo rates are in brackets.
| Label (trials) | Nausea | Vomiting | Diarrhea | Stopped for side effects |
|---|---|---|---|---|
| Wegovy 2.4 mg (STEP 1 to 3, 68 weeks) | 44% (16%) | 24% (6%) | 30% (16%) | 6.8% (3.2%) |
| Zepbound 5 to 15 mg (SURMOUNT-1 and 2, 72 weeks) | 25% to 29% (8%) | 8% to 13% (2%) | 19% to 23% (8%) | 4.8% to 6.7% (3.4%) |
Wegovy prescribing information, Table 3; Zepbound prescribing information, Table 1.1,2 For the head-to-head picture, use the SURMOUNT-5 table above. More in Mounjaro side effects, which covers tirzepatide, and Ozempic side effects, which covers semaglutide.
Worth knowing about both
- Shared warnings: pancreatitis, gallbladder problems, kidney problems from dehydration and severe stomach side effects, and a request to tell your care team before surgery or sedation.1,2
- Hair loss: both weight-management labels say it was associated with weight reduction.1,2
- The contraceptive pill: tirzepatide's labels advise switching to a non-oral method, or adding a barrier method, for 4 weeks after starting and after each dose increase; Wegovy's label has no such instruction.1,2,3
- Higher-dose semaglutide: in the 72-week trials of Wegovy 7.2 mg, 22% on 7.2 mg reported dysesthesia (altered skin sensation, such as burning or skin pain), against 6% on 2.4 mg and 0.3% on placebo.2
In Handle
A daily check-in that takes seconds
Handle asks about nausea every day, plus the few symptoms you choose, such as vomiting, heartburn or food noise. It stays the same short card, whatever you answer, on either medicine.
Some answers, such as severe nausea, come with a clear next step, like contacting your care team. Handle never diagnoses, and it is not a monitoring or emergency service: if you feel very unwell, contact your clinician or emergency services directly.
- Nausea every day; other symptoms if you switch them on
- Up to six extra tracked symptoms, or one in your own words
- Missed a day? Add it later, up to 30 days back
Muscle loss: what the lean-mass data show
Both labels say their medicine lowers body weight with more fat lost than lean mass.1,2 The head-to-head results summarized here don't include body composition, so there's no like-for-like comparison of the two.
In a SURMOUNT-1 substudy of 160 people measured by DXA scan, about 75% of the weight lost on tirzepatide was fat and 25% lean mass, the same split seen with placebo.10 A 2025 analysis of 22 randomized trials of GLP-1 medicines likewise found lean mass made up about 25% of total weight lost.11
Lean mass isn't the same as muscle: it also includes organs, bone and fluid, and studies vary widely in how much lean mass they report lost.12 If muscle matters to you, ask your prescriber or a dietitian about protein and strength training, and whether they'd set targets for you.
In Handle
Protein, fluids and strength sessions, side by side
Log food and drinks to see your protein and fluid totals, and record resistance and cardio sessions, which Handle counts separately. If your clinician sets a protein target, you can record it with who set it; Handle never invents one, and it never estimates muscle from any of this. More in the GLP-1 food tracker guide.
- Protein and fluid totals for the day
- Resistance and cardio counted separately, never merged
- Targets only if your clinician set them
Food noise: what is and isn't known
"Food noise" isn't a term used in the labels or trials cited here. The labels describe effects on appetite and food intake: GLP-1 regulates appetite and calorie intake, and nonclinical studies suggest GIP may add to that.1 Neither head-to-head trial reported on food noise, so there's no evidence here that one quiets it more than the other.
If it matters to you, switch on food noise as a question in Handle's daily check-in and bring the record to your prescriber. Handle shows it beside your doses and never claims one caused the other.
Doses and forms: facts, not instructions
Semaglutide injections come in 0.25 to 2 mg as Ozempic and 0.25 to 7.2 mg as Wegovy, and semaglutide tablets in several strengths for weight (the Wegovy pill) and diabetes (Rybelsus and Ozempic tablets).2,4,5 Tirzepatide comes in 2.5 to 15 mg as pens, vials and KwikPens under both brands.1,3
Labels start low and step up gradually, and your prescriber sets the steps. There's no conversion between the two molecules, and each product has its own missed-dose rule, so ask your prescriber or pharmacist. Handle records what happened and never tells you to catch up.
Switching from semaglutide to tirzepatide, or back
A switch is your prescriber's decision, including when and at what dose; milligrams don't convert between the molecules. The weight-management labels for both say they're not recommended alongside another GLP-1 medicine.1,2
Worth recording: the date, amount and site of your last dose of one and your first of the other, how you feel over the first weeks, and your weekly weight trend. In Handle, both medicines stay on one record, and Journey draws your dose as a step line under your weight, so the switch is easy to find. See the semaglutide tracker and tirzepatide tracker.
Questions to bring to your prescriber
Useful whichever medicine you're offered. A consultation report, part of Premium in the iPhone app, can bring your own record to the same conversation; see preparing for a GLP-1 doctor appointment.
- Which brand fits what I need it for, and why that one?
- Would an injection or a daily pill suit my routine and my other medicines better?
- What result would tell us it's working, and when will we review it?
- Which side effects should I call you about, and which can I manage at home?
- Should we set protein or activity targets while I'm losing weight?
- Does my coverage differ between the two, and would a switch change that?
Questions people ask
Which is better, semaglutide or tirzepatide?+
It depends what you need it for. In the head-to-head trials, tirzepatide led to more weight loss on average in adults without type 2 diabetes (−20.2% on 10 or 15 mg vs −13.7% on semaglutide 1.7 or 2.4 mg over 72 weeks, counting everyone randomized) and lowered HbA1c a little more in type 2 diabetes.6,3 Semaglutide has approvals and forms tirzepatide doesn't, including a pill and kidney and liver indications on some brands.2,4 The choice is one to make with your prescriber.
Is tirzepatide better than semaglutide for weight loss?+
In the one head-to-head trial at weight-management doses, tirzepatide led to more weight loss on average: in SURMOUNT-5, weight changed by −20.2% on tirzepatide (10 or 15 mg) and −13.7% on semaglutide (1.7 or 2.4 mg) over 72 weeks, counting everyone randomized, and 31.6% against 16.1% lost at least a quarter of their weight.6,7 Averages aren't promises, and the trial didn't include people with type 2 diabetes.
Which is safer, tirzepatide or semaglutide?+
Neither has been shown to be safer. They share a boxed warning and most of their warnings, such as pancreatitis and gallbladder disease.1,2 In SURMOUNT-5, serious adverse events were reported in 4.8% on tirzepatide and 3.5% on semaglutide, and 6.1% against 8.0% stopped because of an adverse event, but the trial wasn't designed to compare safety.7,8
Does tirzepatide cause more muscle loss than semaglutide?+
There's no head-to-head answer in the evidence here. Both labels say more fat than lean mass is lost.1,2 In a SURMOUNT-1 substudy, about 25% of weight lost on tirzepatide was lean mass, the same share as on placebo, and an analysis of 22 trials found about 25% across GLP-1 medicines.10,11 Lean mass also includes organs, bone and fluid, so it isn't the same as muscle.12
Is tirzepatide a GLP-1?+
Yes, and more: tirzepatide activates the GLP-1 receptor and also the GIP receptor, which is why its labels call it a GIP and GLP-1 receptor agonist.1,3 Semaglutide activates the GLP-1 receptor only.4 Both are usually grouped together as GLP-1 medicines.
What are the brand names for semaglutide and tirzepatide?+
In the US, semaglutide is sold as Ozempic (weekly injection, and newer daily tablets) and Rybelsus for type 2 diabetes, and as Wegovy (weekly injection or daily pill) for weight management.2,4,5 Tirzepatide is sold as Mounjaro for type 2 diabetes and Zepbound for weight management and sleep apnea.1,3 In the UK, Mounjaro covers weight management too.
Which causes more hair loss, tirzepatide or semaglutide?+
In SURMOUNT-5, hair loss was reported by 8.3% on tirzepatide and 6.1% on semaglutide, though the trial wasn't designed to compare safety.7,8 Both weight-management labels say hair loss in their trials was associated with weight reduction.1,2 If it worries you, note when it started and mention it at your next appointment.
Does semaglutide or tirzepatide reduce food noise more?+
There's no evidence either way in the trials cited here: "food noise" isn't a label or trial term, and neither head-to-head trial reported on it. The labels describe effects on appetite and food intake.1 You can switch on food noise in Handle's daily check-in and bring that record to your prescriber.
Can Handle track semaglutide and tirzepatide?+
Yes. Ozempic, Wegovy, Rybelsus, Mounjaro and Zepbound are in Handle's medicine list, and newer pills can be added under "Something else" with their name and daily schedule. Log each dose and site, answer a short daily check-in, and keep weight, food and fluids alongside. If you switch, both medicines stay on one record, all on the free plan.
Sources
- Eli Lilly and Company, via DailyMed (U.S. National Library of Medicine). Zepbound (tirzepatide) injection — Prescribing Information, effective August 28, 2026.
- Novo Nordisk, via DailyMed (U.S. National Library of Medicine). Wegovy (semaglutide) injection and tablets — Prescribing Information, effective June 18, 2026.
- Eli Lilly and Company, via DailyMed (U.S. National Library of Medicine). Mounjaro (tirzepatide) injection — Prescribing Information, effective August 27, 2026.
- Novo Nordisk, via DailyMed (U.S. National Library of Medicine). Ozempic (semaglutide) injection — Prescribing Information, effective June 1, 2026.
- Novo Nordisk, via DailyMed (U.S. National Library of Medicine). Rybelsus and Ozempic (semaglutide) tablets — Prescribing Information, effective January 30, 2026.
- Aronne LJ et al., New England Journal of Medicine 2025;393:26–36, via PubMed. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), May 11, 2025.
- Eli Lilly and Company (press release). Zepbound (tirzepatide) showed superior weight loss over Wegovy (semaglutide) in complete SURMOUNT-5 results published in The New England Journal of Medicine, May 11, 2025.
- ClinicalTrials.gov (U.S. National Library of Medicine). A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5, NCT05822830): results.
- Frías JP et al., New England Journal of Medicine 2021;385:503–515, via PubMed. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2), 2021.
- Look M et al., Diabetes, Obesity and Metabolism 2025;27:2720–2729, via PubMed. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight, 2025.
- Karakasis P et al., Metabolism 2025;164:156113, via PubMed. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis, 2025.
- Neeland IJ et al., Diabetes, Obesity and Metabolism 2024;26 Suppl 4:16–27, via PubMed. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies, 2024.
Written by the Handle team from the sources above, last checked on September 23, 2026. How we write: our editorial policy. Spotted something out of date? Tell us at [email protected].
Handle supports recording and conversations with your care team. It does not diagnose, and it never tells you to start, change, skip or stop a dose. This page is general information, not medical advice. Always follow your prescriber and your medicine's instructions for use.