Peptide Monographs

Semaglutide and Tirzepatide side by side

Semaglutide and Tirzepatide are both indexed under Incretin receptor agonists. Every cell below carries the record it came from, and an axis with no retrieved value reads Unknown rather than being filled by inference.

Summary

Both compounds are incretin receptor agonists, and the retrieved literature contains a direct head-to-head randomised trial between them: a 2021 New England Journal of Medicine report of once-weekly tirzepatide versus once-weekly semaglutide in patients with type 2 diabetes. The primary documented difference is receptor coverage: semaglutide is a single-receptor GLP-1 agonist, while tirzepatide is reported as a dual GIP and GLP-1 receptor agonist.

[1, 2, 3]

Side by side

Curated comparison axes for Semaglutide and Tirzepatide
AxisSemaglutideTirzepatide
Reported mechanismAgonist at the glucagon-like peptide-1 receptor, the single-receptor mechanism of the incretin receptor agonist class.[3, 11] (derived value: Derived: the retrieved citation metadata for this compound does not state the receptor in a title. The receptor mechanism is taken from the cited 2024 GLP-1 receptor review, and this compound is placed in that class by the cited 2024 BMJ network meta-analysis of GLP-1 receptor agonists.)Dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 receptor.[2]
Molecular formulaC187H291N45O59[4]C225H348N48O68[12]
Molecular weight4114 g/mol[4]4813 g/mol[12]
FDA application registerA query of the FDA Drugs@FDA application register on 2026-10-09 returned 1 application record(s) for this compound name (including NDA213051, marketed as OZEMPIC, RYBELSUS). Material supplied as a research chemical is not the subject of those applications and is not an FDA-approved product.[5]A query of the FDA Drugs@FDA application register on 2026-10-09 returned 2 application record(s) for this compound name (including NDA215866, NDA217806, marketed as MOUNJARO, MOUNJARO KWIKPEN, MOUNJARO (AUTOINJECTOR), ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR)). Material supplied as a research chemical is not the subject of those applications and is not an FDA-approved product.[13]
Reported half-lifeUnknown No pharmacokinetics source was retrieved in v1. PubChem does not carry half-life as a property, so this is recorded as not yet sourced rather than estimated.Unknown No pharmacokinetics source was retrieved in v1. PubChem does not carry half-life as a property, so this is recorded as not yet sourced rather than estimated.

Where the two literatures diverge

Receptor coverage diverges: the cited 2021 Lancet trial report names tirzepatide a dual GIP and GLP-1 receptor agonist, whereas no retrieved title attributes GIP receptor activity to semaglutide. Molecular size diverges on the retrieved PubChem records, tirzepatide being the larger molecule by formula and molecular weight. The FDA application register returned one application record for semaglutide and two for tirzepatide on the retrieval date. Half-life is not sourced for either compound in v1, so that axis renders as Unknown on both sides rather than being filled by inference.

[1, 2, 3]

Where this page sits

Full pages: Semaglutide and Tirzepatide.

Shared class: Incretin receptor agonists.

Other pairs in the same class

All side-by-side pages: index.

Sources

  1. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med (2021). pmid:34170647
  2. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet (2021). pmid:34186022
  3. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduct Target Ther (2024). pmid:39289339
  4. PubChem Compound Summary for CID 56843331, Semaglutide. PubChem, National Library of Medicine (2026). pubchem:56843331
  5. Drugs@FDA application register query for this compound, 1 application(s) returned: NDA213051. U.S. Food and Drug Administration, openFDA drugsfda endpoint (2026). fda:semaglutide
  6. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med (2016). pmid:27633186
  7. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med (2021). pmid:33567185
  8. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med (2023). pmid:37952131
  9. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med (2021). pmid:33185364
  10. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med (2024). pmid:38785209
  11. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ (2024). pmid:38286487
  12. PubChem Compound Summary for CID 166567236, tirzepatide. PubChem, National Library of Medicine (2026). pubchem:166567236
  13. Drugs@FDA application register query for this compound, 2 application(s) returned: NDA215866, NDA217806. U.S. Food and Drug Administration, openFDA drugsfda endpoint (2026). fda:tirzepatide
  14. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med (2022). pmid:35658024
  15. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med (2024). pmid:38856224
  16. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med (2025). pmid:39555826

On each stated value was matched to the record cited for it. That is record matching, not an appraisal of the research. Compiled and checked by: Peptide Monographs editorial desk. No qualified clinical reviewer.

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