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

Purpose 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). Methods 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. Results 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. Conclusions 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. Trial registration ClinicalTrial.gov Identifier: NCT02851745.