ArticleDiabetes, obesity & metabolism2020
A second-generation glucagon-like peptide-1 receptor agonist mitigates vomiting and anorexia while retaining glucoregulatory potency in lean diabetic and emetic mammalian models.
Article in Diabetes, obesity & metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- GLP-1R biased cAMP agonism maintains glycemic control with reduced malaise and emesis in preclinical mammalian models.Diabetes, obesity & metabolism · 2026Article
- Hypophagia and body weight loss by tirzepatide are accompanied by fewer GI adverse events compared to semaglutide in preclinical models.Science advances · 2025Article
- Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data.Current obesity reports · 2025Review
- GLP-1R in diabetes mellitus: from basic discovery to therapeutics development.Frontiers in pharmacology · 2025Review
- The antiemetic actions of GIP receptor agonism.American journal of physiology. Endocrinology and metabolism · 2024Review
- GLP-1 Receptor Agonists in Weight Loss and Bariatric Surgery: Balancing Efficacy and Gastrointestinal Adverse Events.Obesity surgery · 2024Article
- GIP receptor agonism blocks chemotherapy-induced nausea and vomiting.Molecular metabolism · 2023Article
- Chronic Semaglutide Treatment in Rats Leads to Daily Excessive Concentration-Dependent Sucrose Intake.Journal of the Endocrine Society · 2023Article
- Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects.Diabetes, obesity & metabolism · 2023Article
- GLP-1R Signaling and Functional Molecules in Incretin Therapy.Molecules (Basel, Switzerland) · 2023Review
- Incretins as a Potential Treatment Option for Gestational Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Glucagon-like peptide-1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?British journal of pharmacology · 2022Review
- GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist-Induced Nausea and Emesis in Preclinical Models.Diabetes · 2021Article
- Synthesis, Optimization, and Biological Evaluation of Corrinated Conjugates of the GLP-1R Agonist Exendin-4.Journal of medicinal chemistry · 2021Article
- GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
aimTo develop a conjugate of vitamin B12 bound to the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex4) that shows reduced penetrance into the central nervous system while maintaining peripheral glucoregulatory function.
methodsWe evaluated whether a vitamin B12 conjugate of Ex4 (B12-Ex4) improves glucose tolerance without inducing anorexia in Goto-Kakizaki (GK) rats, a lean type 2 diabetes model of an understudied but medically compromised population of patients requiring the glucoregulatory effects of GLP-1R agonists without anorexia. We also utilized the musk shrew (Suncus murinus), a mammalian model capable of emesis, to test B12-Ex4 on glycaemic profile, feeding and emesis.
resultsIn both models, native Ex4 and B12-Ex4 equivalently blunted the rise in blood glucose levels during a glucose tolerance test. In both GK rats and shrews, acute Ex4 administration decreased food intake, leading to weight loss; by contrast, equimolar administration of B12-Ex4 had no effect on feeding and body weight. There was a near absence of emesis in shrews given systemic B12-Ex4, in contrast to reliable emesis produced by Ex4. When administered centrally, both B12-Ex4 and Ex4 induced similar potency of emesis, suggesting that brain penetrance of B12-Ex4 is required for induction of emesis.
conclusionsThese findings highlight the potential therapeutic value of B12-Ex4 as a novel treatment for type 2 diabetes devoid of weight loss and with reduced adverse effects and better tolerance, but similar glucoregulation to current GLP-1R agonists.
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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 Socratic graph.