Evidence mapPaperPMID 37729025Full record

ReviewAmerican journal of physiology. Endocrinology and metabolism2023

Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets.

Franco Folli, Giovanna Finzi, Roberto Manfrini, Alessandra Galli, Francesca Casiraghi, Lucia Centofanti, Cesare Berra, Paolo Fiorina, Alberto Davalli, Stefano La Rosa and 2 more

Open access · hybridAbstract readReview
In one paragraph

Review in American journal of physiology. Endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. The role of the incretin GIP in inflammation.Journal of endocrinological investigation · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. GPCR drug discovery: new agents, targets and indications.Nature reviews. Drug discovery · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 7 institutions in 2 countries.

Franco FolliDipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.ORCID 0000-0001-9824-5222
Giovanna FinziUnit of Pathology, Department of Oncology, ASST Sette Laghi, Varese, Italy.
Roberto ManfriniDipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.
Alessandra GalliDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Francesca CasiraghiDipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.
Lucia CentofantiDipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.
Cesare BerraIRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Paolo FiorinaInternational Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano, Milan, Italy.
Alberto DavalliDiabetes and Endocrinology Unit, Department of Internal Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Stefano La RosaUnit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy.
Carla PeregoDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Paul B HigginsDepartment of Life & Physical Sciences, Atlantic Technological University, Letterkenny, Ireland.ORCID 0000-0003-0882-623X
University of Milan · ITAtlantic Technological UniversityAziende Socio Sanitarie Territoriale dei Sette LaghiBoston Children's Hospital · USMultiMedica · ITUniversity of Insubria · ITVita-Salute San Raffaele University · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Simultaneous activation of the incretin G-protein-coupled receptors (GPCRs) via unimolecular dual-receptor agonists (UDRA) has emerged as a new therapeutic approach for type 2 diabetes. Recent studies also advocate triple agonism with molecules also capable of binding the glucagon receptor. In this scoping review, we discuss the cellular mechanisms of action (MOA) underlying the actions of these novel and therapeutically important classes of peptide receptor agonists. Clinical efficacy studies of several UDRAs have demonstrated favorable results both as monotherapies and when combined with approved hypoglycemics. Although the additive insulinotropic effects of dual glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic peptide receptor (GIPR) agonism were anticipated based on the known actions of either glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP) alone, the additional benefits from GCGR were largely unexpected. Whether additional synergistic or antagonistic interactions among these G-protein receptor signaling pathways arise from simultaneous stimulation is not known. The signaling pathways affected by dual- and tri-agonism require more trenchant investigation before a comprehensive understanding of the cellular MOA. This knowledge will be essential for understanding the chronic efficacy and safety of these treatments.

Indexed as

Diabetes Mellitus, Type 2Islets of LangerhansGastric Inhibitory PolypeptideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHumansIncretinsReceptors, GlucagonGastric Inhibitory PolypeptideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorIncretinsReceptors, Glucagonglucagonglucagon-like peptide 1glucose-dependent insulinotropic peptideislets of Langerhanstype 2 diabetes mellitus

Identifiers

PMID37729025
PMCPMC10874655
OpenAlexW4386887016

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.