Evidence mapPaperPMID 33880754Full record

ReviewBritish journal of pharmacology2022

The therapeutic potential of GLP-1 receptor biased agonism.

Ben Jones

Registry-linked trialOpen access · hybridAbstract readReview
In one paragraph

Review in British journal of pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07713992 (Efficacy and Safety of Mazdutide in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Nonalcoholic Fatty Liver Disease Previously Treated With Semaglutide), which is not on this map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
6.6field-weighted citation impact, top 2% 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.

NCT07713992 nanot yet recruitingstarted 2026, after this paper: background citation

Efficacy and Safety of Mazdutide in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Nonalcoholic Fatty Liver Disease Previously Treated With Semaglutide: A Multicenter, Prospective, Randomized Controlled Trial (IIT)

Ran2026Enrolled72Registered outcomes20Posted comparisons0ConditionsNonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus, Type 2 Diabetes Mellitus (T2DM)ArmsMazdutide(Dual GLP-1R/GCGR Agonist), Semaglutide (1 Mg Dose)
Open the trial in the graph
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 84 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Rewriting Diabetes Therapy: How Incretin Modulation is Transforming Cardiovascular and Renal Outcomes.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Biased Allosteric Modulation in GPCR Drug Discovery.Handbook of experimental pharmacology · 2026
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. What is the pipeline for future medications for obesity?International journal of obesity (2005) · 2025
    Review
  19. Article
  20. Review
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

1 author at 1 institution in 1 country.

Ben JonesSection of Endocrinology and Investigative Medicine, Imperial College London, London, UK.
Imperial College London · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MR/K023667/1Medical Research Council MR/R010676/1
6 · The paper itself

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective treatments for type 2 diabetes as they stimulate insulin release and promote weight loss through appetite suppression. Their main side effect is nausea. All approved GLP-1 agonists are full agonists across multiple signalling pathways. However, selective engagement with specific intracellular effectors, or biased agonism, has been touted as a means to improve GLP-1 agonists therapeutic efficacy. In this review, I critically examine how GLP-1 receptor-mediated intracellular signalling is linked to physiological responses and discuss the implications of recent studies investigating the metabolic effects of biased GLP-1 agonists. Overall, there is little conclusive evidence that beneficial and adverse effects of GLP-1 agonists are attributable to distinct, nonoverlapping signalling pathways. Instead, G protein-biased GLP-1 agonists appear to achieve enhanced anti-hyperglycaemic efficacy by avoiding GLP-1 receptor desensitisation and downregulation, partly via reduced β-arrestin recruitment. This effect seemingly applies more to insulin release than to appetite regulation and nausea, possible reasons for which are discussed. At present, most evidence derives from cellular and animal studies, and more human data are required to determine whether this approach represents a genuine therapeutic advance. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsAnimalsGlucagon-Like Peptide 1InsulinNauseaGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsInsulinappetite regulationbiased agonismglucagon-like peptide-1 receptorinsulin releaseβ-arrestin

Identifiers

PMID33880754
PMCPMC8820210
OpenAlexW3156815314

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.