Evidence map›Paper›PMID 38878772›Full record

ArticleCell metabolism2024

Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor.

Ajit Regmi, Eitaro Aihara, Michael E Christe, Gabor Varga, Thomas P Beyer, Xiaoping Ruan, Emily Beebe, Libbey S O'Farrell, Melissa A Bellinger, Aaron K Austin and 15 more

Erratum issued Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07567378 (Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts), which is not on this map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT07567378 not yet recruitingstarted 2026, after this paper: background citation

Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts (CARTIZ): A Prospective Observational Multi-Institutional Registry of the VAT-Articular-Cardiac-Aging Axis in Adults Exposed to Tirzepatide in Mexico, With Quantitative Knee Cartilage T2 Mapping, Cardiac CT Epicardial Adipose Tissue Radiomic Phenotyping, HLA Stratification, Longitudinal Multi-Frequency Bioimpedance Body Composition, and a Prespecified Surgical Tissue Acquisition Subcohort

Ran2026Enrolled30Registered outcomes14Posted comparisons0ConditionsAtrial Fibrillation (AF), Coronary Artery Disease, Diabetes (DM), Heart FailureArmsTirzepatide
PMID 41406444PMID 40903131PMID 41666927PMID 39566869PMID 41928037PMID 28701474PMID 30170852PMID 32154773PMID 41903163PMID 41944220PMID 42010357other papers from this trial
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3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Ajit RegmiEli Lilly and Company, Indianapolis, IN 46285, USA.
Eitaro AiharaEli Lilly and Company, Indianapolis, IN 46285, USA.
Michael E ChristeEli Lilly and Company, Indianapolis, IN 46285, USA.
Gabor VargaEli Lilly and Company, Indianapolis, IN 46285, USA.
Thomas P BeyerEli Lilly and Company, Indianapolis, IN 46285, USA.
Xiaoping RuanEli Lilly and Company, Indianapolis, IN 46285, USA.
Emily BeebeEli Lilly and Company, Indianapolis, IN 46285, USA.
Libbey S O'FarrellEli Lilly and Company, Indianapolis, IN 46285, USA.
Melissa A BellingerEli Lilly and Company, Indianapolis, IN 46285, USA.
Aaron K AustinEli Lilly and Company, Indianapolis, IN 46285, USA.
Yanzhu LinEli Lilly and Company, Indianapolis, IN 46285, USA.
Haitao HuEli Lilly and Company, Indianapolis, IN 46285, USA.
Debra L KonkolEli Lilly and Company, Indianapolis, IN 46285, USA.
Samantha WojnickiEli Lilly and Company, Indianapolis, IN 46285, USA.
Adrienne K HollandEli Lilly and Company, Indianapolis, IN 46285, USA.
Jessica L FriedrichEli Lilly and Company, Indianapolis, IN 46285, USA.
Robert A BrownEli Lilly and Company, Indianapolis, IN 46285, USA.
Amanda S EstelleEli Lilly and Company, Indianapolis, IN 46285, USA.
Hannah S BadgerEli Lilly and Company, Indianapolis, IN 46285, USA.
Gabriel S GaidoshEli Lilly and Company, Indianapolis, IN 46285, USA.
Sander KooijmanDepartment of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Patrick C N RensenDepartment of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Tamer CoskunEli Lilly and Company, Indianapolis, IN 46285, USA.
Melissa K ThomasEli Lilly and Company, Indianapolis, IN 46285, USA.
William RoellEli Lilly and Company, Indianapolis, IN 46285, USA. Electronic address: bill_roell@lilly.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist, has, in clinical trials, demonstrated greater reductions in glucose, body weight, and triglyceride levels compared with selective GLP-1R agonists in people with type 2 diabetes (T2D). However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte and mouse models, we investigated how long-acting GIPR agonists regulate fasted and fed adipocyte functions. In functional assays, GIPR agonism enhanced insulin signaling, augmented glucose uptake, and increased the conversion of glucose to glycerol in a cooperative manner with insulin; however, in the absence of insulin, GIPR agonists increased lipolysis. In diet-induced obese mice treated with a long-acting GIPR agonist, circulating triglyceride levels were reduced during oral lipid challenge, and lipoprotein-derived fatty acid uptake into adipose tissue was increased. Our findings support a model for long-acting GIPR agonists to modulate both fasted and fed adipose tissue function differentially by cooperating with insulin to augment glucose and lipid clearance in the fed state while enhancing lipid release when insulin levels are reduced in the fasted state.

Indexed as

AdipocytesGastric Inhibitory PolypeptideReceptors, Gastrointestinal HormoneAnimalsGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like Peptide-2 ReceptorGlucoseHumansInsulinLipolysisMaleMiceMice, Inbred C57BLNutrientsObesityGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like Peptide-2 ReceptorGlucoseInsulinNutrientsReceptors, Gastrointestinal HormoneTirzepatideTriglyceridesadipocyteadiposecarbohydrate metabolismGIPGLP-1insulinlipid metabolismnutrient partitioningtirzepatide

Identifiers

PMID38878772

What Socratic holds

Texttitle and abstract
Read underepoch 390

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.