ArticleProceedings of the National Academy of Sciences of the United States of America2022
Structural determinants of dual incretin receptor agonism by tirzepatide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 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
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential.BMC ophthalmology · 2026 · on this mapPooled it
- Efficacy and safety of tirzepatide in patients with type 2 diabetes: A systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Glycemic and bodyweight effects ofScience advances · 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
- Article
- Tirzepatide-associated interstitial kidney injury.JCEM case reports · 2026Article
- Tirzepatide in Obesity-Related Obstructive Sleep Apnea: Beyond Weight Loss Toward Disease Modification?Life (Basel, Switzerland) · 2026Review
- Core conformation of arrestin coupling to parathyroid hormone type 1 receptor.Nature communications · 2026Article
- Obesity medications and acquired hypothalamic obesity in adults: A two-case experience.Obesity pillars · 2026Article
- Designing Rigid Protein Fiducials to Visualize GPCR Conformational States.bioRxiv : the preprint server for biology · 2026Article
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Human class B1 GPCR modulation by plasma membrane lipids.Communications biology · 2026Article
- GPCR Biased Signaling in Metabolism.Handbook of experimental pharmacology · 2026Review
- Beyond glycemic control: clinical cardiovascular effects of tirzepatide-a narrative review.Therapeutic advances in endocrinology and metabolism · 2026Review
- Tirzepatide for obesity without diabetes: mechanistic insights, clinical evidence, and future directions.Frontiers in pharmacology · 2026Review
- Comparative Efficacy of Semaglutide and Tirzepatide in Chinese Adults with Obesity without Diabetes: A Real-World Observational Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Dual incretin analogue tirzepitide - SURMOUNTing the challenge of obesity induced obstructive sleep apnea.World journal of experimental medicine · 2025Review
- Oral Treatment of Obesity by GLP-1 and Its Analogs.Pharmaceutics · 2025Review
- The Genetic Blueprint of Obesity: From Pathogenesis to Novel Therapies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist.
Indexed as
Identifiers
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.