Evidence map›Paper›PMID 29724198›Full record

Trial reportCardiovascular diabetology2018

The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.

Fiona J Dore, Cleyton C Domingues, Neeki Ahmadi, Nabanita Kundu, Yana Kropotova, Sara Houston, Carol Rouphael, Aytan Mammadova, Linda Witkin, Anamil Khiyami and 2 more

Registry-linked trialOpen access · goldFull text readClinical Trial, Phase IVRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cardiovascular diabetology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02024477 (Effect of Saxagliptin), which is not on this map. Cited by 30 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 4 pooled it
2.3field-weighted citation impact, top 11% 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.

NCT02024477 phase4completednot on this map

Effect of Saxagliptin (DPP-4 Inhibitor) on Endothelial Progenitor Cells (EPCs) as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early Type 2 Diabetes Patients

TypeinterventionalSponsorGeorge Washington UniversityRan2013 to 2017Enrolled42ConditionsType 2 DiabetesArmsSaxagliptin, Placebo
3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 4 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Impact of DPP-4 Inhibitors on Interleukin Levels in Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2025
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. 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
  10. Article
  11. Article
  12. Review
  13. Article
  14. Endothelial progenitor cells in pregnancy-related diseases.Clinical science (London, England : 1979) · 2023
    Review
  15. Review
  16. Review
  17. Repurposing Metformin for Vascular Disease.Current medicinal chemistry · 2023
    Review
  18. Observational
  19. Article
  20. Article
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

12 authors at 5 institutions in 2 countries.

Fiona J DoreThe GW Medical Faculty Associates, Washington, DC, USA.
Cleyton C DominguesDepartment of Medicine, The George Washington University, 2300 Eye Street, Washington, DC, 20037, USA.
Neeki AhmadiDepartment of Medicine, The George Washington University, 2300 Eye Street, Washington, DC, 20037, USA.
Nabanita KunduDepartment of Medicine, The George Washington University, 2300 Eye Street, Washington, DC, 20037, USA.
Yana KropotovaDepartment of Medicine, The George Washington University, 2300 Eye Street, Washington, DC, 20037, USA.
Sara HoustonDepartment of Medicine, The George Washington University, 2300 Eye Street, Washington, DC, 20037, USA.
Carol RouphaelDepartment of Medicine, The George Washington University, 2300 Eye Street, Washington, DC, 20037, USA.
Aytan MammadovaThe GW Medical Faculty Associates, Washington, DC, USA.
Linda WitkinThe GW Medical Faculty Associates, Washington, DC, USA.
Anamil KhiyamiThe GW Medical Faculty Associates, Washington, DC, USA.
Richard L AmdurThe GW Medical Faculty Associates, Washington, DC, USA.
Sabyasachi SenThe GW Medical Faculty Associates, Washington, DC, USA. ssen1@gwu.edu.ORCID 0000-0002-3675-9129
George Washington University · USGW Medical Faculty Associates · USCleveland Clinic · USPrincess Nourah bint Abdulrahman University · SARichmond University Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsType 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients.

methodsIn 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for < 10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (p < 0.05).

resultsAlthough there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (p < 0.05) and a downregulation in CD34- cells for IL-6 (p < 0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (p < 0.05).

conclusionSaxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477.

Indexed as

AdamantaneAdultAgedAntigens, CD34Arterial PressureBiomarkersDiabetes Mellitus, Type 2DipeptidesDipeptidyl-Peptidase IV InhibitorsDistrict of ColumbiaDouble-Blind MethodDrug SynergismDrug Therapy, CombinationEndothelial Progenitor CellsEndothelium, VascularFemaleAdamantaneAntigens, CD34BiomarkersDipeptidesDipeptidyl-Peptidase IV InhibitorsHypoglycemic AgentsMetforminsaxagliptinArterial stiffnessDiabetesDPP-4 inhibitorEndothelial progenitor cellsSaxagliptin

Identifiers

PMID29724198
PMCPMC5934787
OpenAlexW2804686821

What OpenQuestion 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 OpenQuestion graph.