Effects of Dipeptidyl Peptidase-4 Inhibitor Linagliptin on Left Ventricular Dysfunction in Patients with Type 2 Diabetes and Concentric Left Ventricular Geometry (the DYDA 2™ Trial). Rationale, Design, and Baseline Characteristics of the Study Population
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A multicentre, randomized, double-blind, placebo-controlled, parallel-group study aimed to define the potential positive effect of dipeptidyl peptidase-4 inhibition on left ventricular systolic function (LVSF) beyond glycemic control in type 2 diabetes mellitus (T2DM) (DYDA 2™ trial).
Individuals with fairly controlled T2DM and asymptomatic impaired LVSF were randomized in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their stable diabetes therapy. Eligibility criteria were age ≥ 40 years, history of T2DM with a duration of at least 6 months, HbA1c ≤ 8.0% (≤ 64 mmol/mol), no history or clinical signs/symptoms of cardiac disease, evidence at baseline echocardiography of concentric LV geometry (relative wall thickness ≥ 0.42), and impaired LVSF defined as midwall fractional shortening (MFS) ≤ 15%. The primary end-point was the modification from baseline to 48 weeks of MFS. As an exploratory analysis, significant changes in LV global longitudinal strain and global circumferential strain, measured by speckle tracking echocardiography, were also considered. Secondary objectives were changes in diastolic and/or in systolic longitudinal function as measured by tissue Doppler.
A total of 188 patients were enrolled. They were predominantly males, mildly obese, with typical insulin-resistance co-morbidities such as hypertension and dyslipidemia. Mean relative wall thickness was 0.51 ± 0.09 and mean MFS 13.3% ± 2.5.
DYDA 2 is the first randomized, double-blind, placebo-controlled trial to explore the effect of a dipeptidyl peptidase-4 inhibitor on LVSF in T2DM patients in primary prevention regardless of glycemic control. The main characteristics of the enrolled population are reported.
ClinicalTrial.gov Identifier: NCT02851745.
KeywordsDipeptidyl peptidase-4 inhibition Linagliptin Type 2 diabetes Glycemic control Concentric geometry Left ventricular dysfunction
CBG, GC, APM literature search, study design, data collection and interpretation, writing; DL data collection, analysis and interpretation; EN, FO literature search, data collection; CM, RL data management, reading and interpretation. No other persons have made substantial contributions to this manuscript. All authors approved the final version.
The sponsors of the study are the Fondazione Associazione Medici Diabetologi and Heart Care Foundation, two non-profit independent organizations, which also own the database. Database management, quality control of the data, and data analyses were under the responsibility of the ANMCO Research Centre of the Heart Care Foundation. The study was partially supported by an unrestricted grant by Boehringer Ingelheim, Italy. The Steering Committee of the study had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of data analysis.
Compliance with Ethical Standards
Conflict of Interest
CBG has nothing to disclose with respect to the present manuscript. In 2018, he received fees from Boehringer Ingelheim, Italy, for data interpretation of other trials. GC, EN, RL, and CM have nothing to disclose. DL is employee of Heart Care Foundation, which conducted the study with an unresctricted grant by Boehringer Ingelheim, Italy. APM nothing to disclose with respect to the present manuscript. Personal fees for participation in study committees sponsored by Bayer, Fresenius, and Novartis.
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.
This article does not contain any study with animals performed by any of the authors.
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