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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2018

Open Access 01-12-2018 | Original investigation

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

Authors: Fiona J. Dore, Cleyton C. Domingues, Neeki Ahmadi, Nabanita Kundu, Yana Kropotova, Sara Houston, Carol Rouphael, Aytan Mammadova, Linda Witkin, Anamil Khiyami, Richard L. Amdur, Sabyasachi Sen

Published in: Cardiovascular Diabetology | Issue 1/2018

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Abstract

Aims

Type 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.

Methods

In 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).

Results

Although 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).

Conclusion

Saxagliptin, 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
Appendix
Available only for authorised users
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Metadata
Title
The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial
Authors
Fiona J. Dore
Cleyton C. Domingues
Neeki Ahmadi
Nabanita Kundu
Yana Kropotova
Sara Houston
Carol Rouphael
Aytan Mammadova
Linda Witkin
Anamil Khiyami
Richard L. Amdur
Sabyasachi Sen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2018
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-018-0709-9

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