Evidence mapPaperPMID 32724076Full record

Trial reportNature communications2020

Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.

Laurie L Baggio, Elodie M Varin, Jacqueline A Koehler, Xiemin Cao, Yuliya Lokhnygina, Susanna R Stevens, Rury R Holman, Daniel J Drucker

Registry-linked trialOpen access · goldFull text readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07241897 (DPP4 Inhibitor on Post-stroke Cognitive Impairment in Ischemic Stroke Patients With Type 2 Diabetes Mellitus), which is not on this map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% 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.

NCT07241897 phase3not yet recruitingnot on this mapstarted 2025, after this paper: background citation

DPP4 Inhibitor on Post-stroke Cognitive Impairment in Ischemic Stroke Patients With Type 2 Diabetes Mellitus (DISC-DM): Multicentre, Double Blind, Randomised, Placebo Controlled Trial

TypeinterventionalSponsorSecond Affiliated Hospital of Soochow UniversityRan2025 to 2028Enrolled312ConditionsIschemic Stroke, Diabete MellitusArmsSentagliptin Phosphate - single dose, Placebo
3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Neurovascular Actions of Dipeptidyl Peptidase-4 Inhibitors and Their Implications for Cognitive Dysfunction in Type 2 Diabetes Mellitus.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Increased Dipeptidyl Peptidase-4 Promotes Adipose Inflammation and Dysfunction in Mice Under Chronic Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025
    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

8 authors at 3 institutions in 3 countries.

Laurie L BaggioDepartment of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada.
Elodie M VarinDepartment of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-1514-2362
Jacqueline A KoehlerDepartment of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada.
Xiemin CaoDepartment of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada.
Yuliya LokhnyginaDuke Clinical Research Institute, Duke University, Durham, NC, USA.
Susanna R StevensDuke Clinical Research Institute, Duke University, Durham, NC, USA.
Rury R HolmanDiabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1256-874X
Daniel J DruckerDepartment of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada. drucker@lunenfeld.ca.ORCID http://orcid.org/0000-0001-6688-8127
Lunenfeld-Tanenbaum Research Institute · CADuke University · USUniversity of Oxford · GB

Funding

Department of Health
6 · The paper itself

Abstract

Dipeptidyl peptidase-4 (DPP4) modulates inflammation by enzymatic cleavage of immunoregulatory peptides and through its soluble form (sDPP4) that directly engages immune cells. Here we examine whether reduction of DPP4 activity alters inflammation. Prolonged DPP4 inhibition increases plasma levels of sDPP4, and induces sDPP4 expression in lymphocyte-enriched organs in mice. Bone marrow transplantation experiments identify hematopoietic cells as the predominant source of plasma sDPP4 following catalytic DPP4 inhibition. Surprisingly, systemic DPP4 inhibition increases plasma levels of inflammatory markers in regular chow-fed but not in high fat-fed mice. Plasma levels of sDPP4 and biomarkers of inflammation are lower in metformin-treated subjects with type 2 diabetes (T2D) and cardiovascular disease, yet exhibit considerable inter-individual variation. Sitagliptin therapy for 12 months reduces DPP4 activity yet does not increase markers of inflammation or levels of sDPP4. Collectively our findings dissociate levels of DPP4 enzyme activity, sDPP4 and biomarkers of inflammation in mice and humans.

Indexed as

AgedAnimalsBiomarkersCardiovascular DiseasesDiabetes Mellitus, Type 2Diet, AtherogenicDiet, High-FatDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDisease Models, AnimalFemaleGlucagon-Like Peptide-1 ReceptorHumansInflammationInflammation MediatorsMaleBiomarkersDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDPP4 protein, humanDpp4 protein, mouseGlp1r protein, mouseGlucagon-Like Peptide-1 ReceptorInflammation MediatorsMetforminProtein IsoformsSitagliptin Phosphate

Identifiers

PMID32724076
PMCPMC7387453
OpenAlexW3045972848

What Socratic holds

Textfull text, public
LicenceCC BY
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.