Data edition of
Residue An evidence-graded reference for peptide science

A peptide class of 4 compounds

Incretin & amylin agonists

Which incretin-class peptides have the strongest human evidence?

Small unlabeled vials of pale amber solution and a glass pipette on ruled paper, an oxblood ribbon curling beside them

The incretin class is the best-studied corner of peptide science. Semaglutide acts on the GLP-1 receptor alone; tirzepatide adds the GIP receptor; retatrutide adds the glucagon receptor as a third target1PubMedTriple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff AM et al. N Engl J Med. 2023.; cagrilintide is a long-acting amylin analog studied mainly in combination with semaglutide2PubMedCoadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT et al. N Engl J Med. 2025..

Two of the four are FDA-approved for chronic weight management and type 2 diabetes3FDADrugs@FDA: WEGOVY, WEGOVY HD, WEGOVY FLEXTOUCH (NDA215256). NOVO; original approval 2021-06-04; Prescription.,4FDADrugs@FDA: ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR) (NDA217806). ELI LILLY AND CO; original approval 2023-11-08; Prescription.. The other two have published phase 3 results but, at our last fetch, no approved application in Drugs@FDA. In the only head-to-head obesity trial among them, tirzepatide produced greater weight reduction than semaglutide at 72 weeks5PubMedTirzepatide as Compared with Semaglutide for the Treatment of Obesity. Aronne LJ et al. N Engl J Med. 2025..

Table 1. Incretin & amylin agonists on Residue, by best evidence grade. Bars show PubMed records on a log scale; counts are from the data edition.
GradeCompoundClassLiteratureRegistered studies
A SemaglutideFDA-approved — Ozempic (2017), Rybelsus (2019), Wegovy (2021) GLP-1 class 5,706 785 · 366 active
A TirzepatideFDA-approved — Mounjaro (2022), Zepbound (2023) GLP-1 class 2,640 300 · 199 active
B RetatrutideInvestigational — not FDA-approved GLP-1 class 207 34 · 11 active
B CagrilintideInvestigational — not FDA-approved GLP-1 class 121 44 · 18 active

Monographs in this class

  • A
    Semaglutide

    The GLP-1 receptor agonist behind Ozempic, Wegovy and Rybelsus, with the largest trial record of any peptide on this site — including a cardiovascular-outcomes trial in people without diabetes.

  • A
    Tirzepatide

    The first approved dual GIP and GLP-1 receptor agonist — and, in the only head-to-head obesity trial, more effective for weight than semaglutide.

  • B
    Retatrutide

    A single peptide that activates three hormone receptors — GIP, GLP-1 and glucagon — now with published phase 3 results, and not yet approved.

  • B
    Cagrilintide

    A long-acting amylin analog from Novo Nordisk, studied alone and — as CagriSema — together with semaglutide in phase 3.

Comparisons

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

  1. 1 PubMed Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med 2023. PMID 37366315; doi:10.1056/NEJMoa2301972.
  2. 2 PubMed Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2025. PMID 40544433; doi:10.1056/NEJMoa2502081.
  3. 3 FDA Drugs@FDA: WEGOVY, WEGOVY HD, WEGOVY FLEXTOUCH (NDA215256). NOVO; original approval 2021-06-04; Prescription.
  4. 4 FDA Drugs@FDA: ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR) (NDA217806). ELI LILLY AND CO; original approval 2023-11-08; Prescription.
  5. 5 PubMed Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025. PMID 40353578; doi:10.1056/NEJMoa2416394.