To evaluate the effect of linagliptin on left ventricular systolic function beyond glycaemic control in type 2 diabetes mellitus. A multicentre, randomised, double-blind, placebo controlled, parallel-group study, was performed (the DYDA 2 trial). Individuals with type 2 diabetes mellitus and asymptomatic impaired left ventricular systolic function were randomly allocated in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their diabetes therapy. Eligibility criteria were age 40 years and older, haemoglobin A1c 8.0% or less (≤64 mmol/mol), no history of cardiac disease, concentric left ventricular geometry (relative wall thickness ≥0.42), impaired left ventricular systolic function defined as midwall fractional shortening 15% or less at baseline echocardiography. The primary end point was the modification of midwall fractional shortening over time. The main secondary objectives were changes in diastolic and/or in longitudinal left ventricular systolic function as measured by tissue Doppler echocardiography. One hundred and eighty-eight patients were enrolled, predominantly men with typical insulin-resistance comorbidities. At baseline, mean midwall fractional shortening was 13.3%±2.5. At final evaluation, 88 linagliptin patients and 86 placebo patients were compared: midwall fractional shortening increased from 13.29 to 13.82 (+4.1%) in the linagliptin group, from 13.58 to 13.84 in the placebo group (+1.8%, analysis of covariance P = 0.86), corresponding to a 2.3-fold higher increase in linagliptin than the placebo group, although non-statistically significant. Also, changes in diastolic and longitudinal left ventricular systolic function did not differ between the groups. Serious adverse events or linagliptin/placebo permanent discontinuation occurred in very few cases and in the same percentage between the groups. In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening. ClinicalTrial.gov (ID NCT02851745).