ArticleNature communications2018
Targeting GLP-1 receptor trafficking to improve agonist efficacy.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 4 of them syntheses that pooled 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.
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.
Who cites it
139 citing papers in PubMed, 4 syntheses or guidelines pooled it, 273 citations in OpenAlex.
- Evaluating biased agonism of glucagon-like peptide-1 (GLP-1) receptors to improve cellular bioenergetics: A systematic review.Diabetes, obesity & metabolism · 2025Pooled it
- Comparative gastrointestinal adverse effects of GLP-1 receptor agonists and multi-target analogs in type 2 diabetes: a Bayesian network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials.Frontiers in public health · 2024Pooled it
- GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.Nature genetics · 2023Pooled it
- Efficacy and safety of CT-868, a novel, fully biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in type 2 diabetes: A double-blind, randomized placebo controlled phase 2 trial.Diabetes, obesity & metabolism · 2026Trial
- The Metabolomic Effects of Tripeptide Gut Hormone Infusion Compared to Roux-en-Y Gastric Bypass and Caloric Restriction.The Journal of clinical endocrinology and metabolism · 2022Trial
- Peptide-functionalized nanoemulsions with exendin-4 as a model ligand.International journal of pharmaceutics: X · 2026Article
- Potent and biased agonists of class B1 GPCRs from a heterochiral design strategy.Nature chemistry · 2026Article
- Discerning protein pools by selective staining with self-labeling tags.FEBS letters · 2026Review
- The evolving therapeutic landscape of gut-pancreatic peptide signalling in metabolic disorders: from mono- to multi-agonist therapies.Bioscience reports · 2026Review
- Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Discovery of Biased Dual-Agonists of Glucagon-Like Peptide 1 and Glucagon Receptors through Mutation of a Conserved Aspartate.ACS medicinal chemistry letters · 2026Article
- Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications.Antibody therapeutics · 2026Review
- Altered Intracellular Trafficking as a Mechanism for Prolonged Duration of G Protein-Coupled Receptor Activation.Journal of the American Chemical Society · 2026Article
- Tirzepatide-associated interstitial kidney injury.JCEM case reports · 2026Article
- Progressive loss of glycemic control during chronic DPP-4 inhibitor therapy despite preserved β-cell function: a case report suggesting acquired incretin resistance.Cardiovascular diabetology. Endocrinology reports · 2026Article
- The molecular mechanisms of incretin resistance in Type 2 Diabetes Mellitus (T2DM).Nutrition & diabetes · 2026Review
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- SfE BES 2026: What's new in basic science endocrinology?The Journal of endocrinology · 2026Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 11 institutions in 8 countries.
Funding
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling. Compared to a panel of FDA-approved GLP-1 mimetics, compounds that retain GLP-1R at the plasma membrane produce greater long-term insulin release, which is dependent on a reduction in β-arrestin recruitment and faster agonist dissociation rates. Such molecules elicit glycemic benefits in mice without concomitant increases in signs of nausea, a common side effect of GLP-1 therapies. Our study identifies a set of agents with specific GLP-1R trafficking profiles and the potential for greater efficacy and tolerability as T2D treatments.
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What OpenQuestion holds
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 OpenQuestion graph.