Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study

OBJECTIVE: We aimed to investigate the effect of liraglutide treatment on heart function in type 2 diabetes (T2D) patients with subclinical heart failure. METHODS: Randomized open parallel-group trial. 62 T2D patients (45 male) with subclinical heart failure were randomized to either once daily liraglutide 1.8 mg, or glimepiride 4 mg, both add on to metformin 1 g twice a day. Mitral annular systolic (s′) and early diastolic (e′) velocities were measured at rest and during bicycle ergometer exercise, using tissue Doppler echocardiography. The primary endpoint was 18-week treatment changes in longitudinal functional reserve index (LFRI(diastolic/systolic)). RESULTS: Clinical characteristics between groups (liraglutide = 33 vs. glimepiride = 29) were well matched. At baseline left ventricle ejection fraction (53.7 vs. 53.6%) and global longitudinal strain (−15.3 vs. −16.5%) did not differ between groups. There were no significant differences in mitral flow velocities between groups. For the primary endpoint, there was no treatment change [95% confidence interval] for: LFRI(diastolic) (−0.18 vs. −0.53 [−0.28, 2.59; p = 0.19]), or LFRI(systolic) (−0.10 vs. −0.18 [−1.0, 1.7; p = 0.54]); for the secondary endpoints, there was a significant treatment change in respect of body weight (−3.7 vs. −0.2 kg [−5.5, −1.4; p = 0.001]), waist circumference (−3.1 vs. −0.8 cm [−4.2, −0.4; p = 0.019]), and heart rate (HR) (6.3 vs. −2.3 bpm [−3.0, 14.2; p = 0.003]), with no such treatment change in hemoglobin A1c levels (−11.0 vs. −9.2 mmol/mol [−7.0, 2.6; p = 0.37]), between groups. CONCLUSION: 18-week treatment of liraglutide compared with glimepiride did not improve LFRI(diastolic/systolic), but however increased HR. There was a significant treatment change in body weight reduction in favor for liraglutide treatment.