Evidence map›Paper›PMID 28683283›Full record

Trial reportCell metabolism2017

Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes.

Elif A Oral, Shannon M Reilly, Andrew V Gomez, Rasimcan Meral, Laura Butz, Nevin Ajluni, Thomas L Chenevert, Evgenia Korytnaya, Adam H Neidert, Rita Hench and 12 more

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
8.6field-weighted citation impact, top 1% of its field
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

101 citing papers in PubMed, 163 citations in OpenAlex.

  1. Article
  2. Review
  3. Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026
    Review
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41 more citing papers are in PubMed but not listed here.

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

22 authors at 4 institutions in 2 countries.

Elif A OralDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA. Electronic address: eliforal@med.umich.edu.
Shannon M ReillyLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Departments of Medicine and Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Andrew V GomezDepartments of Medicine and Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Rasimcan MeralDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Laura ButzDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Nevin AjluniDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Thomas L ChenevertDepartment of Radiology, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Evgenia KorytnayaDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Adam H NeidertDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Rita HenchDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Diana RusDivision of Metabolism, Endocrinology, and Diabetes, Department of Medicine, and Brehm Center for Diabetes, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Jeffrey F HorowitzSchool of Kinesiology, University of Michigan, Ann Arbor, MI 48019, USA.
BreAnne PoirierLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Peng ZhaoLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Departments of Medicine and Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Kim LehmannDepartments of Medicine and Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Mohit JainDepartments of Medicine and Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Ruth YuGene Expression Laboratory, Salk Institute for Biological Sciences, La Jolla, CA 92037, USA.
Christopher LiddleGene Expression Laboratory, Salk Institute for Biological Sciences, La Jolla, CA 92037, USA; Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.
Maryam AhmadianGene Expression Laboratory, Salk Institute for Biological Sciences, La Jolla, CA 92037, USA.
Michael DownesGene Expression Laboratory, Salk Institute for Biological Sciences, La Jolla, CA 92037, USA.
Ronald M EvansGene Expression Laboratory, Salk Institute for Biological Sciences, La Jolla, CA 92037, USA.
Alan R SaltielLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Departments of Medicine and Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA; Institute of Diabetes and Metabolic Health, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0757, USA. Electronic address: asaltiel@ucsd.edu.
University of Michigan · USUniversity of California San Diego · USSalk Institute for Biological Studies · USWestmead Hospital · AU

Funding

PILOT STUDIES--GASTROINTESTINAL HORMONE RESEARCH CORE CENTERP30DK034933 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1986 to 2005
$6.0M
Pilot & Feasibility ProgramP30DK063491 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2003 to 2025
$5.4M
Pilot and Feasibility ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$4.9M
HORMONAL REGULATION OF MAMMALIAN GENE EXPRESSIONR37DK057978 · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2000 to 2005
$4.2M
Signaling Pathways in Insulin ActionR01DK060591 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2002 to 2005
$1.4M
Pilot and Feasibility (P and F) ProgramP30DK089503 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$1.2M
NCATS NIH HHS UL1 TR000433NCATS NIH HHS UL1 TR002240NHLBI NIH HHS P01 HL088093NHLBI NIH HHS R01 HL105278NIDDK NIH HHS K01 DK105075NIDDK NIH HHS K01 DK113065NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK089503NIDDK NIH HHS R01 DK057978NIDDK NIH HHS R01 DK060591NIDDK NIH HHS R01 DK076906NIDDK NIH HHS R01 DK100319NIDDK NIH HHS R21 DK098776NIDDK NIH HHS R24 DK090962NIDDK NIH HHS R37 DK057978
6 · The paper itself

Abstract

Numerous studies indicate an inflammatory link between obesity and type 2 diabetes. The inflammatory kinases IKKɛ and TBK1 are elevated in obesity; their inhibition in obese mice reduces weight, insulin resistance, fatty liver and inflammation. Here we studied amlexanox, an inhibitor of IKKɛ and TBK1, in a proof-of-concept randomized, double-blind, placebo-controlled study of 42 obese patients with type 2 diabetes and nonalcoholic fatty liver disease. Treatment of patients with amlexanox produced a statistically significant reduction in Hemoglobin A1c and fructosamine. Interestingly, a subset of drug responders also exhibited improvements in insulin sensitivity and hepatic steatosis. This subgroup was characterized by a distinct inflammatory gene expression signature from biopsied subcutaneous fat at baseline. They also exhibited a unique pattern of gene expression changes in response to amlexanox, consistent with increased energy expenditure. Together, these data suggest that dual-specificity inhibitors of IKKɛ and TBK1 may be effective therapies for metabolic disease in an identifiable subset of patients.

Indexed as

AgedAminopyridinesBlood GlucoseDiabetes Mellitus, Type 2Double-Blind MethodEnergy MetabolismFemaleGlycated HemoglobinHumansI-kappa B KinaseMaleMiddle AgedNon-alcoholic Fatty Liver DiseaseObesityProtein Kinase InhibitorsProtein Serine-Threonine KinasesAminopyridinesamlexanoxBlood GlucoseGlycated Hemoglobinhemoglobin A1c protein, humanI-kappa B KinaseProtein Kinase InhibitorsProtein Serine-Threonine KinasesTBK1 protein, humanamlexanoxclinical trialenergy expenditurefatty livergene expressioninflammationobesityprotein kinase

Identifiers

PMID28683283
PMCPMC5663294
OpenAlexW2725509061

What Socratic holds

Textmetadata
LicenceTDM
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.