Evidence map›Paper›PMID 41509321›Full record

ArticlebioRxiv : the preprint server for biology2025

Tirzepatide Synergizes with Leptin on Weight Loss and Restoring Metabolic Homeostasis in Diet-induced Obesity Model.

Xun Sun, Yuexi Yin, Min Song, Brian A Droz, Yanzhu Lin, Kristen N Beaty, Baohua Zhou, Hyun Cheol Roh, Jonathan M Wilson, Paul F Cain and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Xun SunHerman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine; Indianapolis, IN, USA.
Yuexi YinStark Neurosciences Research Institute, Indiana University School of Medicine; Indianapolis, IN, USA.
Min SongLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Brian A DrozLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Yanzhu LinLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Kristen N BeatyCenter for Diabetes and Metabolic Diseases, Indiana University School of Medicine; Indianapolis, IN, USA.
Baohua ZhouHerman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine; Indianapolis, IN, USA.
Hyun Cheol RohCenter for Diabetes and Metabolic Diseases, Indiana University School of Medicine; Indianapolis, IN, USA.ORCID 0000-0002-8176-5747
Jonathan M WilsonLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Paul F CainLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Ricardo J SammsLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Patrick L SheetsStark Neurosciences Research Institute, Indiana University School of Medicine; Indianapolis, IN, USA.
Minrong AiLilly Research Laboratories, Eli Lilly and Company; Indianapolis, IN, USA.
Hongxia RenHerman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine; Indianapolis, IN, USA.ORCID 0000-0003-2909-4365

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Translation CoreP30DK097512 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Tamara S Hannon · 2015 to 2026
$17.4M
Metabolic Function of Gpr17 in Gastrointestinal TractR01DK120772 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI REN, HONGXIA · 2020 to 2024
$2.0M
Illuminating the Metabolic Function of GPR162 by Delineating Downstream Signaling Pathways and Characterizing Hypothalamic Expression PatternR03TR003350 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI REN, HONGXIA, WATTS, VAL J · 2020 to 2020
$172k
NCATS NIH HHS R03 TR003350NCATS NIH HHS UL1 TR002529NIDDK NIH HHS P30 DK097512NIDDK NIH HHS R01 DK120772
6 · The paper itself

Abstract

Leptin resistance limits anti-obesity efficacy. We identified a leptin-sensitizing mechanism through tirzepatide (TZP), a glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonist. Our tirzepatide clinical trial revealed that circulating leptin levels at baseline correlated with weight loss efficacy in patients with obesity, suggesting leptin and tirzepatide could interact to achieve stronger effects on weight loss. Next, we utilized the diet-induced obesity (DIO) mice and demonstrated the synergistic effects of tirzepatide and leptin combination (TZP+Lep) on weight loss. TZP+Lep treatment further improved hepatic insulin sensitivity and upregulated thermogenetic gene expression in brown adipose tissue. Metabolic profiling under thermoneutrality revealed TZP+Lep treatment further reduced food intake and increased energy expenditure. Tirzepatide sensitized leptin signaling in hypothalamic pro-opiomelanocortin (POMC) and GLP-1R expressing neurons. TZP+Lep synergistically increased POMC neuronal firing by decreasing the inhibitory postsynaptic input. Together, our work showed combining tirzepatide and leptin as a potential way for better maintenance of metabolic homeostasis in obesity management.

Identifiers

PMID41509321
PMCPMC12776102

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.