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Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial

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Abstract

Aims

Several trials have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors, used to treat type 2 diabetes (T2DM), improve endothelial function. The current study investigated the effects of vildagliptin, a DPP-4 inhibitor, compared to glibenclamide on endothelial function, arterial stiffness, and blood pressure in patients with T2DM and hypertension.

Methods

Patients aged over 35 years with T2DM and hypertension, but without cardiovascular disease, were randomly allocated to treatment with vildagliptin (n = 25) or glibenclamide (n = 25). Both groups took metformin. Endothelial function was evaluated by peripheral artery tonometry (Endo-PAT 2000) to calculate the reactive hyperemia index (RHI) and arterial stiffness. Primary outcome was change in the RHI after 12 weeks of treatment. Twenty-four-hour non-invasive ambulatory blood pressure monitoring was performed using a Mobil-O-Graph® 24-h PWA monitor. Arterial stiffness was assessed using the augmentation index corrected for 75 bpm (AIx75), pulse wave velocity (PWV) and central systolic blood pressure (cSBP).

Results

There were no changes in the RHI in the vildagliptin group (before 2.35 ± 0.59; after 2.24 ± 0.60; p value = NS) or in the glibenclamide group (before 2.36 ± 0.52; after 2.34 ± 0.50; p value = NS), with no differences between groups (p value = NS). There was also no difference between vildagliptin and glibenclamide treatment in respect to AIx75 (p value = NS), cSBP (p value = NS) or PWV (p value = NS).

Conclusions

Vildagliptin and glibenclamide similarly do not change the endothelial function and arterial stiffness after 12 weeks of treatment in diabetic and hypertensive patients without cardiovascular disease. Thus, vildagliptin has a neutral effect on vascular function.

Trial registration

ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

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Abbreviations

ABPM:

Ambulatory blood pressure monitoring

AIx:

Augmentation index

BMI:

Body mass index

BP:

Blood pressure

CAD:

Coronary artery disease

cSBP:

Central systolic blood pressure

CVD:

Cardiovascular disease

DBP:

Diastolic BP

DPP-4:

Dipeptidyl peptidase-4

eGFR:

Estimated glomerular filtration ratio

Endo-PAT 2000:

Peripheral artery tonometry

FMD:

Flow-mediated vasodilatation

GLP-1:

Glucagon-like peptide-1

HbA1c:

Glycated hemoglobin

HDLc:

High-density lipoprotein cholesterol

LDLc:

Low-density lipoprotein cholesterol

MBP:

Mean BP

PP:

Pulse pressure

PWV:

Pulse wave velocity

RHI:

Reactive hyperemia index

SBP:

Systolic BP

SD:

Standard deviation

T2DM:

Type 2 diabetes

TC:

Total cholesterol

TG:

Triglycerides

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Acknowledgements

The authors would like to thank the patients and staff who are participating in this clinical trial. We thank the reviewer David Hewitt for correcting both the English spelling and grammar and Lilian Castiglioni for the statistical analysis.

Funding

This study was sponsored by Novartis. However, Novartis did not have any influence on the study design, methods, data management or analysis.

Author information

Authors and Affiliations

  1. Internal Medicine Division, Hospital de Base, State Medical School at São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil

    Luciana Neves Cosenso-Martin

  2. Hypertension Clinic, State Medical School at São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil

    Luiz Tadeu Giollo-Júnior, Letícia Aparecida Barufi Fernandes & Juan Carlos Yugar-Toledo

  3. Hypertension Clinic, State Nursing School at São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil

    Cláudia Bernardi Cesarino

  4. Cardiology Department, Hospital de Base, State Medical School at São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil

    Marcelo Arruda Nakazone & Maurício de Nassau Machado

  5. Hypertension Clinic, Internal Medicine Department, Hospital de Base, State Medical School at São José do Rio Preto (FAMERP), Ave Brig. Faria Lima 5416, São José do Rio Preto, 15090-000, São Paulo, Brazil

    José Fernando Vilela-Martin

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  1. Luciana Neves Cosenso-Martin
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Contributions

LNC-M and JFV-M contributed to the concept and design of this ongoing study. MAN and MNM take responsibility for the integrity of the data and accuracy of data analysis. LNC-M, LTG, LABF, CBC, JCY-T and JFV-M helped with the literature search. All authors read and approved the final manuscript. LNC-M and JFV-M wrote the manuscript.

Corresponding author

Correspondence to José Fernando Vilela-Martin.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Ethics approval and consent to participate

The study protocol (no. 11665513.7.00005415) was approved by the Research Ethics Committee of State Medical School at Sao Jose do Rio Preto (FAMERP) and the study was conducted in accordance with the principles of the Helsinki Declaration.

Consent for publications

Not applicable.

Conflict of interest

Jose F Vilela-Martin has received research grants from Novartis. The other authors do not have a conflict of interest.

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Cosenso-Martin, L.N., Giollo-Júnior, L.T., Fernandes, L.A.B. et al. Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial. Acta Diabetol 55, 1237–1245 (2018). https://doi.org/10.1007/s00592-018-1204-1

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