Trial reportScience translational medicine2013
Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans.
Trial report in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02598791 (GIP/GLP-1 Co-Activity in Subjects With Obesity), which is not on this map. Cited by 305 papers, 1 of them a synthesis 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.
GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake
Open the trial in the graphWho cites it
305 citing papers in PubMed, 1 synthesis or guideline pooled it, 661 citations in OpenAlex.
- Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025 · on this mapPooled it
- GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.Diabetologia · 2026Trial
- Efficacy and safety of CT-868, a novel, fully biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in type 2 diabetes: A double-blind, randomized placebo controlled phase 2 trial.Diabetes, obesity & metabolism · 2026Trial
- A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings.Nature metabolism · 2024Trial
- Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2021Trial
- GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Pediatric Obesity: From Neuroendocrine Mechanisms to Clinical Application.International journal of molecular sciences · 2026Review
- GLP-1 and dual GIP/GLP-1 receptor agonists' psychopharmacology and putative neuropsychiatric associated effects: a Bradford Hill-informed, systematic, evaluation.Current psychiatry reports · 2026Review
- Anti-Obesity Medications in Longevity and Aesthetic Medicine.Journal of clinical medicine · 2026Review
- Personalization of incretin therapy: can GLP-1 and GIP receptor polymorphisms influence therapy response?Journal of the Endocrine Society · 2026Review
- GIP in Cardiovascular and Kidney Disease: From Physiology to Pharmacology.Diabetes, obesity & metabolism · 2026Review
- A Review of Lifestyle Interventions Provided as an Adjunct to Obesity Management Medications.Obesity science & practice · 2026Review
- Clinical Potential of GIP in Type 2 Diabetes and Obesity.Diabetes care · 2026Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Oral Health Implications of GLP-1 Receptor Agonists and Other Incretin-Based Therapies.Journal of clinical medicine · 2026Review
- Do Fasting GLP-1 and GIP Levels Predict the Initial Pharmacological Response to Semaglutide and Tirzepatide?Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Recent advances in incretin biology and therapeutics: From glucose-dependent insulinotropic polypeptide reappraisal to next-generation agonists.Journal of diabetes investigation · 2026Review
- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating ghrelin-GLP-1 receptor signaling pathway.JCI insight · 2026Article
- Article
245 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
33 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the discovery and translational therapeutic efficacy of a peptide with potent, balanced co-agonism at both of the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This unimolecular dual incretin is derived from an intermixed sequence of GLP-1 and GIP, and demonstrated enhanced antihyperglycemic and insulinotropic efficacy relative to selective GLP-1 agonists. Notably, this superior efficacy translated across rodent models of obesity and diabetes, including db/db mice and ZDF rats, to primates (cynomolgus monkeys and humans). Furthermore, this co-agonist exhibited synergism in reducing fat mass in obese rodents, whereas a selective GIP agonist demonstrated negligible weight-lowering efficacy. The unimolecular dual incretins corrected two causal mechanisms of diabesity, adiposity-induced insulin resistance and pancreatic insulin deficiency, more effectively than did selective mono-agonists. The duration of action of the unimolecular dual incretins was refined through site-specific lipidation or PEGylation to support less frequent administration. These peptides provide comparable pharmacology to the native peptides and enhanced efficacy relative to similarly modified selective GLP-1 agonists. The pharmacokinetic enhancement lessened peak drug exposure and, in combination with less dependence on GLP-1-mediated pharmacology, avoided the adverse gastrointestinal effects that typify selective GLP-1-based agonists. This discovery and validation of a balanced and high-potency dual incretin agonist enables a more physiological approach to management of diseases associated with impaired glucose tolerance.
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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.