ReviewEndocrine reviews2018
Targeting the Incretin/Glucagon System With Triagonists to Treat Diabetes.
Review in Endocrine reviews, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 149 citations in OpenAlex.
- SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans.Diabetes · 2021Trial
- Peptide Marriages: Modular Assembly of Multi-Agonist Therapeutics.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Emerging role of GLP-1 mono, dual, and triple agonists in the management of MASH-related fibrosis.Cell reports. Medicine · 2026Review
- A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.Science advances · 2026Article
- Design of a metabolically-stable peptide therapeutic with triple-hormone-receptor agonist activity.Journal of computer-aided molecular design · 2026Article
- Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders.Clinical and molecular hepatology · 2026Review
- Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice.GeroScience · 2026Article
- Prolonged Somatostatin Receptor 2 Antagonism Enhances Glucagon Response to Hypoglycemia in Male Diabetic Rats.Endocrinology · 2026Article
- Early metabolic predictors of type 2 diabetes mellitus in normoglycemic adults: insights from six-year prospective cohort study.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Review Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD.Alimentary pharmacology & therapeutics · 2025Review
- The Incretin Effect of Yerba Maté (Nutrients · 2025Article
- Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression.npj metabolic health and disease · 2025Article
- Central and peripheral neural circuits regulating glucose homeostasis.npj biomedical innovations · 2025Review
- Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng.Acta pharmaceutica Sinica. B · 2024Article
- Article
- Review
- Glucagon kinetics assessed by mathematical modelling during oral glucose administration in people spanning from normal glucose tolerance to type 2 diabetes.Frontiers in endocrinology · 2024Article
- Impaired incretin homeostasis in non-diabetic moderate-severe CKD.medRxiv : the preprint server for health sciences · 2023Article
- Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets.American journal of physiology. Endocrinology and metabolism · 2023Review
- Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness.Diabetes, obesity & metabolism · 2023Article
8 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
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Glucagonlike peptide 1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of glucagonlike peptide 1 receptor-directed strategies is submaximal, and the only potent, sustainable treatment of metabolic dysfunction is bariatric surgery, necessitating the development of unique therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors. In this review, we discuss the range of tissue targets and added benefits afforded by the inclusion of each of GIP and glucagon. We discuss considerations for the development of sequence-intermixed dual agonists and triagonists, highlighting the importance of evaluating balanced signaling at the targeted receptors. Several multireceptor agonist peptides have been developed and evaluated, and the key preclinical and clinical findings are reviewed in detail. The biological activity of these multireceptor agonists are founded in the success of GLP-1-directed strategies; by including GIP and glucagon components, these multireceptor agonists are thought to enhance GLP-1's activities by broadening the tissue targets and synergizing at tissues that express multiple receptors, such at the brain and pancreatic islet β cells. The development and utility of balanced, unimolecular multireceptor agonists provide both a useful tool for querying the actions of incretins and glucagon during metabolic disease and a unique drug class to treat type 2 diabetes with unprecedented efficacy.
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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.