Trial reportProceedings of the National Academy of Sciences of the United States of America2020
Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 3 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
59 citing papers in PubMed, 3 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- New Mediators in the Crosstalk between Different Adipose Tissues.International journal of molecular sciences · 2024Pooled it
- Liver Brain Interactions: Focus on FGF21 a Systematic Review.International journal of molecular sciences · 2022Pooled it
- Bispecific Antibodies: From Research to Clinical Application.Frontiers in immunology · 2021Pooled it
- Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of FGF21 and GDF15.Journal of cellular biochemistry · 2026Review
- Agonistic bispecific antibodies: an emerging frontier in antibody therapeutics.Journal of translational medicine · 2026Review
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Identification of candidate nsSNPs of the human FNDC5 gene and their structural and functional consequences using in silico analysis.Scientific reports · 2025Article
- Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2025Review
- Insulin-sensitizing effects of fibroblast growth factor-21 in underfed sheep.Journal of animal science · 2025Article
- Impaired Fibroblast Growth Factor 21 (FGF21) Associated with Visceral Adiposity Leads to Insulin Resistance: The Core Defect in Diabetes Mellitus.Current diabetes reviews · 2025Review
- Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.International journal of biological sciences · 2025Review
- Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data.Molecular metabolism · 2024Article
- Therapeutic effects of FGF21 mimetic bFKB1 on MASH and atherosclerosis in Ldlr-/-.Leiden mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids.Cell reports. Medicine · 2024Article
- Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans WithJournal of the Endocrine Society · 2024Article
- The state of the art in secondary pharmacology and its impact on the safety of new medicines.Nature reviews. Drug discovery · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.
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What Socratic 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 Socratic graph.