Pinc PeptideThe girly peptide research blog

Compare · updated 8 October 2026

Semaglutide vs tirzepatide

The short answer

In the head-to-head SURMOUNT-5 trial, tirzepatide caused more weight loss than semaglutide: 20.2% versus 13.7% of body weight after 72 weeks4. The trial enrolled 751 adults with obesity but without type 2 diabetes, was open-label (everyone knew which drug they got) and was funded by Lilly, which makes tirzepatide45. Nausea and diarrhea were about equally common on both drugs, while vomiting was less common on tirzepatide (15.0% versus 21.3%)1. Both are FDA-approved medicines67. Gray-market vials are another matter: in Finnrick’s latest completed tests, 37.8% of semaglutide and 30.1% of tirzepatide samples failed, as of 30 September 202689.

At a glance

ComparedSemaglutideTirzepatide
Evidence tierA Two or more large human trialsA Two or more large human trials
Does it work?For long-term weight management: Benefit shownIn a large trial, people lost 14.9% of their weight on average over 68 weeks, versus 2.4% on placebo10. A higher 7.2 mg weekly dose cut weight by 18.7%, versus 3.9% on placebo11.For weight loss and weight maintenance: Benefit shownIn a large trial, people lost 20.9% of their weight on average over 72 weeks on the top dose, versus 3.1% on placebo12. Weight tends to return after stopping13.
FDAApproved (Wegovy, Ozempic, Rybelsus)614Approved (Zepbound, Mounjaro)7
US pharmaciesCopies limited since the shortage ended1516Copies limited since the shortage ended15
SportNot banned, but monitored1718Not banned, but monitored1718
AustraliaPrescription only19Prescription only19
Half-lifeAbout 1 week20About 5 to 6 days5
Taken asSubcutaneous injection once weekly (approved as Ozempic and Wegovy; human trial data)
Oral tablet once daily (approved as Rybelsus, Ozempic tablets and Wegovy tablets; human trial data)
Unapproved “research” vials sold for injection (no quality control; no trials of these products found)		Subcutaneous injection, once weekly (the only approved route and the route used in all trials cited here)
What it isA modified version of the human gut hormone GLP-1 (94% the same sequence) that switches on one target, the GLP-1 receptor20.A lab-made peptide that switches on two targets, the receptors for the gut hormones GIP and GLP-15.
Approved uses in the USWegovy injection: weight reduction in adults and in children 12 and older with obesity, lowering heart risk in adults with heart disease and obesity or overweight, and the liver disease MASH with moderate to advanced scarring20. Wegovy tablets: weight reduction and heart risk in adults20. Ozempic: type 2 diabetes, including heart and kidney risk reduction21.Zepbound: weight reduction and long-term maintenance in adults, and moderate to severe obstructive sleep apnea in adults with obesity5. Mounjaro: type 2 diabetes in adults and children 10 and older, and heart risk reduction in adults with type 2 diabetes at high risk22.
Weight loss head to head (SURMOUNT-5, 72 weeks)13.7% of body weight lost on the highest tolerated dose, 1.7 or 2.4 mg a week; waist down 13.0 cm4.20.2% of body weight lost on the highest tolerated dose, 10 or 15 mg a week; waist down 18.4 cm4.
Blood sugar head to head (SURPASS-2, type 2 diabetes, 40 weeks)In 1,879 adults with type 2 diabetes, HbA1c (a measure of average blood sugar) fell 1.86 percentage points on 1 mg a week2.HbA1c fell 2.01, 2.24 and 2.30 percentage points on 5, 10 and 15 mg a week, and weight fell 1.9 to 5.5 kg more than on semaglutide2.
Largest outcome trialSELECT, 17,604 adults with heart or blood-vessel disease and overweight, no diabetes: heart attack, stroke or cardiovascular death in 6.5% versus 8.0% on placebo over about 40 months23.SURPASS-CVOT, 13,299 adults with type 2 diabetes and heart or blood-vessel disease: 12.2% versus 13.1% on dulaglutide, an older GLP-1 drug; as good as, but not shown to be better than, the comparator24.
Common side effects versus placebo (each drug’s label)Wegovy 2.4 mg: nausea 44% versus 16%, diarrhea 30% versus 16%, vomiting 24% versus 6%, constipation 24% versus 11%20.Zepbound 5 to 15 mg: nausea 25% to 29% versus 8%, diarrhea 19% to 23% versus 8%, vomiting 8% to 13% versus 2%, constipation 11% to 17% versus 5%5.
Stopped because of side effects (each drug’s label)6.8% on Wegovy 2.4 mg versus 3.2% on placebo in the weight-loss trials20.4.8%, 6.3% and 6.7% on Zepbound 5, 10 and 15 mg versus 3.4% on placebo, mostly in the first few months5.
Gray-market vials74 of Finnrick’s latest 196 completed tests failed (37.8%) as of 30 September 20268. Fake semaglutide containing insulin has caused severe low blood sugar25.59 of Finnrick’s latest 196 completed tests failed (30.1%) as of 30 September 20269. Two counterfeit tirzepatide pens detained in Ireland contained insulin26.

How they work differently

Semaglutide copies one gut hormone, GLP-1, which helps regulate appetite and how much people eat20. Tirzepatide acts on the GLP-1 receptor too, and also on the receptor for GIP (glucose-dependent insulinotropic polypeptide), a second gut hormone5. The Zepbound label says lab and animal studies suggest the GIP part may add to the effect on food intake5.

Otherwise the two labels describe similar effects: both drugs reduce calorie intake, cause more fat loss than lean-tissue loss, and slow the emptying of the stomach520.

Which causes more side effects?

SURMOUNT-5 gave both drugs in the same trial, so its numbers compare like with like4. In its results posted to the trial registry, nausea (43.6% on tirzepatide versus 44.4% on semaglutide), diarrhea (23.5% versus 23.4%) and constipation (27.0% versus 28.5%) were about equally common1.

Vomiting (15.0% versus 21.3%) and acid reflux (6.1% versus 10.6%) were less common on tirzepatide, while injection-site reactions (8.6% versus 0.3%) and hair loss (8.3% versus 6.1%) were more common1. Serious adverse events, the most severe category, affected 4.8% on tirzepatide and 3.5% on semaglutide, and six people in each group left the study because of an adverse event1.

Most digestive side effects in both groups were mild to moderate and came mainly while the dose was being raised4. Setting the two labels’ tables side by side is less reliable, because both warn that their rates cannot be directly compared with rates from another drug’s trials520.

What about the 7.2 mg dose of semaglutide?

Since 19 March 2026, the Wegovy label has allowed up to 7.2 mg a week (Wegovy HD) for adults who have tolerated 2.4 mg for at least 4 weeks and need more weight loss620. SURMOUNT-5 used semaglutide only up to 2.4 mg, so it does not show how 7.2 mg compares with tirzepatide4.

In STEP UP, 7.2 mg cut weight by 18.7% at 72 weeks, against 15.6% on 2.4 mg and 3.9% on placebo11. Side effects rose with the dose: digestive problems affected 70.8% on 7.2 mg versus 61.2% on 2.4 mg, and dysesthesia (unusual or unpleasant skin sensations) 22.9% versus 6.0%11.

Questions people ask

Is tirzepatide stronger than semaglutide?

For weight loss, yes in SURMOUNT-5, the head-to-head obesity trial: 20.2% versus 13.7% of body weight at 72 weeks4. In type 2 diabetes, tirzepatide also lowered HbA1c and weight more than semaglutide 1 mg in SURPASS-22. Lilly, which makes tirzepatide, funded both trials24.

Is Mounjaro the same as Zepbound, and Ozempic the same as Wegovy?

Each pair shares an active ingredient: Mounjaro and Zepbound are tirzepatide, and Ozempic and Wegovy are semaglutide5202122. They are approved for different uses and dose ranges: Ozempic tops out at 2 mg a week for type 2 diabetes, while Wegovy goes to 2.4 mg, or 7.2 mg for some adults2021. Mounjaro and Zepbound both top out at 15 mg a week in adults522.

Can you switch from semaglutide to tirzepatide?

Neither US label gives directions for switching from one drug to the other520. Both labels advise against combining their drug with another GLP-1 receptor agonist, a group that includes both of them520. Any switch is a decision for a prescriber.

Do you regain weight after stopping semaglutide or tirzepatide?

On average, yes: in STEP 4, people switched to placebo after 20 weeks on semaglutide saw their weight rise 6.9% over the next 48 weeks, while those who stayed on it lost a further 7.9%3. In SURMOUNT-4, people switched to placebo after 36 weeks on tirzepatide saw their weight rise 14.0% over 52 weeks, while those who stayed on it lost a further 5.5%13.

Which causes more nausea, semaglutide or tirzepatide?

In SURMOUNT-5, nausea was about equally common: 44.4% on semaglutide and 43.6% on tirzepatide1. Vomiting was more common on semaglutide, 21.3% versus 15.0%1.

Go deeper

Sources

  1. 1A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5), NCT05822830: posted results ClinicalTrials.gov, 26 Nov 2025. clinicaltrials.gov
  2. 2Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes New England Journal of Medicine, 5 Aug 2021. pubmed.ncbi.nlm.nih.gov
  3. 3Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial JAMA, 13 Apr 2021. pubmed.ncbi.nlm.nih.gov
  4. 4Tirzepatide as Compared with Semaglutide for the Treatment of Obesity New England Journal of Medicine, 3 Jul 2025. pubmed.ncbi.nlm.nih.gov
  5. 5ZEPBOUND (tirzepatide) injection, for subcutaneous use: prescribing information Eli Lilly and Company via DailyMed (U.S. National Library of Medicine), 28 Aug 2026. dailymed.nlm.nih.gov
  6. 6Drugs@FDA: applications containing semaglutide (NDA 209637, 213051, 213182, 215256, 218316; ANDA 220314) U.S. Food and Drug Administration (openFDA), 29 Sep 2026. api.fda.gov · data query
  7. 7Drugs@FDA via openFDA: approval history for NDA 215866 (Mounjaro) and NDA 217806 (Zepbound) U.S. Food and Drug Administration (openFDA), accessed 1 Oct 2026. api.fda.gov · data query
  8. 8Semaglutide: public lab test results (Finnrick product page) Finnrick, 29 Sep 2026. finnrick.com
  9. 9Tirzepatide: vendor test results Finnrick, 29 Sep 2026. finnrick.com
  10. 10Once-Weekly Semaglutide in Adults with Overweight or Obesity New England Journal of Medicine, 2021. pubmed.ncbi.nlm.nih.gov
  11. 11Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial The Lancet Diabetes & Endocrinology, Nov 2025. pubmed.ncbi.nlm.nih.gov
  12. 12Tirzepatide Once Weekly for the Treatment of Obesity New England Journal of Medicine, 21 Jul 2022. pubmed.ncbi.nlm.nih.gov
  13. 13Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial JAMA, 2 Jan 2024. pubmed.ncbi.nlm.nih.gov
  14. 14FDA approves Novo Nordisk’s Wegovy pill, the first and only oral GLP-1 for weight loss in adults Novo Nordisk (PR Newswire), 22 Dec 2025. prnewswire.com
  15. 15FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize U.S. Food and Drug Administration, 1 Apr 2026. fda.gov
  16. 16Outsourcing Facilities Ass’n v. FDA, No. 25-10758 (5th Cir.) (unpublished, per curiam; revised) US Court of Appeals for the Fifth Circuit, 1 Sep 2026. ca5.uscourts.gov
  17. 17The 2026 Monitoring Program World Anti-Doping Agency, Sep 2025. wada-ama.org
  18. 18World Anti-Doping Code International Standard: Prohibited List 2026 World Anti-Doping Agency, 24 Sep 2025. wada-ama.org
  19. 19Therapeutic Goods (Poisons Standard—October 2026) Instrument 2026 (F2026L01327) Federal Register of Legislation, Australian Government, 28 Sep 2026. legislation.gov.au
  20. 20WEGOVY (semaglutide) injection and tablets: prescribing information (SPL version 19) Novo Nordisk via DailyMed (U.S. National Library of Medicine), 30 Jun 2026. dailymed.nlm.nih.gov
  21. 21OZEMPIC (semaglutide) injection: prescribing information (SPL version 20) Novo Nordisk via DailyMed (U.S. National Library of Medicine), 10 Jun 2026. dailymed.nlm.nih.gov
  22. 22MOUNJARO (tirzepatide) injection, for subcutaneous use: prescribing information Eli Lilly and Company via DailyMed (U.S. National Library of Medicine), 27 Aug 2026. dailymed.nlm.nih.gov
  23. 23Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes New England Journal of Medicine, 2023. pubmed.ncbi.nlm.nih.gov
  24. 24Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes New England Journal of Medicine, 18 Dec 2025. pubmed.ncbi.nlm.nih.gov
  25. 25[Insulin intoxications caused by falsified semaglutide] Nederlands Tijdschrift voor Geneeskunde, 29 Jun 2026. pubmed.ncbi.nlm.nih.gov
  26. 26HPRA health warning after detention of counterfeit tirzepatide pens containing insulin Health Products Regulatory Authority (Ireland), 10 Oct 2025. hpra.ie

Not medical advice. Neither compound is recommended here. How we grade evidence · Report an error.