ArticleNature communications2022
Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
What it found
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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
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis.Acta diabetologica · 2025Pooled it
- Basal insulin intensification with GLP-1RA and dual GIP and GLP-1RA in patients with uncontrolled type 2 diabetes mellitus: A rapid review of randomized controlled trials and meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Structural basis for small-molecule agonism at GCGR and GIPR via a conserved intracellular allosteric site.Acta pharmacologica Sinica · 2026Article
- Skeletal Muscle Effects of GLP 1 Receptor Agonists: Molecular Mechanisms and Comparative Insights on Semaglutide and Tirzepatide, a Narrative Review.International journal of molecular sciences · 2026Review
- Impact of Semaglutide, Liraglutide and Tirzepatide on Cardiometabolic Outcomes: A Comparative Narrative Review.Endocrinology, diabetes & metabolism · 2026Review
- The Neuroprotective Potentials of Dual GIP/GLP1-RA (Tirzepatide): From Preclinical Experiments to Clinical Trials: A Scoping Review.Brain and behavior · 2026Article
- The Pleiotropic Therapeutic Perspectives of GLP-1 and GIP Receptor Agonists in Spinal Cord Injury: A Narrative Review.Molecular neurobiology · 2026Review
- Design of a metabolically-stable peptide therapeutic with triple-hormone-receptor agonist activity.Journal of computer-aided molecular design · 2026Article
- Structural Dynamics of GLP-1 Analogues: Folding Energetics, Lipidation-Driven Assembly, and Aggregation Mechanisms.Molecules (Basel, Switzerland) · 2026Review
- Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation.Endocrine · 2026Review
- Acute Contractile Effects of Glucagon-like-Peptide-1 Receptor Agonists in the Human Heart.Pharmaceutics · 2026Review
- Crystallization and 1.6 Å resolution crystal structure of an acylated GLP-1/GIP analogue peptide.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Systemic Pharmacokinetic Principles of Therapeutic Peptides.Clinical pharmacokinetics · 2026Article
- Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors.Acta pharmacologica Sinica · 2026Article
- IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes.Pharmacological research · 2026Review
- An Insight into Pharmaceutical Design and Pharmacokinetic Characteristics of GLP-1 RAs.Current pharmaceutical design · 2026Review
- Beyond glycemic control: clinical cardiovascular effects of tirzepatide-a narrative review.Therapeutic advances in endocrinology and metabolism · 2026Review
- Effect of a Low Electrostatic Environment on the Helical Structures of Peptides and Proteins Using Flexible Water Models: An In Silico Study.ACS omega · 2025Article
- Protein-Ligand Interactions in Cardiometabolic Drug Targets: Focus on Weight Loss and Cardioprotection.Molecules (Basel, Switzerland) · 2025Review
- Novel Peptides as GIPR/GLP-1R/GCGR Triagonists for Treating Type 2 Diabetes Mellitus.ACS medicinal chemistry letters · 2025Article
13 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
22 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dual agonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their multiplexed pharmacological actions over monoagonists such as semaglutide, we determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR. The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the near-atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility of tirzepatide and peptide 20.
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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.