ArticleNature communications2020
Molecular engineering of safe and efficacious oral basal insulin.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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
18 citing papers in PubMed, 56 citations in OpenAlex.
- Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing.BMJ open diabetes research & care · 2021Trial
- Design, Preparation and Activity Evaluation of Long-Acting Insulin Analogues.The protein journal · 2026Article
- Nanoparticle-Based Oral Insulin Delivery: Challenges, Advances, and Future Directions.Pharmaceutics · 2025Review
- Permeation Enhancer-based Ionogel Shows Remarkable Potential for Oral Insulin Delivery.Advanced healthcare materials · 2025Article
- Design of a novel long-acting insulin analogs by acetylation modification and compared with insulin Icodec.Scientific reports · 2025Article
- Once-Weekly Insulin Icodec in Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (ONWARDS Clinical Program).Biomedicines · 2024Review
- Toward once-monthly insulin therapyRSC chemical biology · 2024Article
- Enhanced disulphide bond stability contributes to the once-weekly profile of insulin icodec.Nature communications · 2024Article
- Pharmacological and Benefit-Risk Profile of Once-Weekly Basal Insulin Administration (Icodec): Addressing Patients' Unmet Needs and Exploring Future Applications.Journal of clinical medicine · 2024Review
- The Current and Promising Oral Delivery Methods for Protein- and Peptide-Based Drugs.International journal of molecular sciences · 2024Review
- Helical-Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Total Chemical Synthesis of Palmitoyl-Conjugated Insulin.ACS omega · 2023Article
- Factors Affecting Performance of Insulin Pen Injector Technology: A Narrative Review.Journal of diabetes science and technology · 2023Review
- Material design for oral insulin delivery.Med-X · 2023Review
- On the Utility of Chemical Strategies to Improve Peptide Gut Stability.Journal of medicinal chemistry · 2022Article
- An integrated platform approach enables discovery of potent, selective and ligand-competitive cyclic peptides targeting the GIP receptor.Chemical science · 2022Article
- Article
- Review: Glucose-sensitive insulin.Molecular metabolism · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 2 institutions in 2 countries.
Funding
Abstract
Recently, the clinical proof of concept for the first ultra-long oral insulin was reported, showing efficacy and safety similar to subcutaneously administered insulin glargine. Here, we report the molecular engineering as well as biological and pharmacological properties of these insulin analogues. Molecules were designed to have ultra-long pharmacokinetic profile to minimize variability in plasma exposure. Elimination plasma half-life of ~20 h in dogs and ~70 h in man is achieved by a strong albumin binding, and by lowering the insulin receptor affinity 500-fold to slow down receptor mediated clearance. These insulin analogues still stimulate efficient glucose disposal in rats, pigs and dogs during constant intravenous infusion and euglycemic clamp conditions. The albumin binding facilitates initial high plasma exposure with a concomitant delay in distribution to peripheral tissues. This slow appearance in the periphery mediates an early transient hepato-centric insulin action and blunts hypoglycaemia in dogs in response to overdosing.
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.