Introduction: Diabetes mellitus (DM) is thought to be highly involved in complex atherothrombogenic processes, but the long-term antiatherosclerotic therapies in patients with type-2 DM have not been established.
Hypothesis: Therefore we assessed hypothesis long-term treatment with linagliptin, an adipofriendly dipeptidyl peptidase-4 inhibitor (DPP4I) , chronically inhibits atherosclerotic progression in patients with type-2 DM receiving statin, one of the best possible antiatherosclerotic treatment.
Methods: Thirty type-2 diabetic patients with stable coronary artery disease were randomized to group-L where they received linagliptin (5mg/day), or to group-C where they received enhanced antidiabetic therapy without a DPP4I for 2 years. We quantified flow-mediated endothelium-dependent dilation of right brachial artery after 5 minutes forearm occlusion (BFMD), and intima-media thickness of brachial artery (BIMT) using high-resolution ultrasonography. We also quantified intima-media thickness of common carotid artery (CIMT) using high-resolution ultrasonography. Changes in BFMD, BIMT, and CIMT were compared between the two study groups.
Results: Group-L (n=20) manifested good compliance to the long-term treatment and improvements in diabetic and lipid variables represented by HbA1c and LDL after long-term medication of linagliptin, while there were no improvements in group-C. BFMD (%) improved after medication in group-L (from 3.8±1.6 to 6.8±2.5, p<0.01) and BIMT (mm) decreased in group-L (from 0.34±0.11 to 0.31±0.10, p=0.03), while both remained unchanged in group-C (BFMD; from 4.0±2.0 to 3.8±1.8, p=0.18, BIMT; from 0.33±0.16 to 0.35±0.19, p=0.14). CIMT (mm) did not increase in group-L (from 1.11±0.38 to 1.09±0.37, p=0.15) but increased in group-C (from 1.09±0.45mm to 1.17±0.49mm, p=0.03). Changes of BFMD or BIMT in group-L did not correlate to those of HbA1c (FMD: r=0.19, p=0.59, BIMT: r=0.13, p=0.80).
Conclusions: This study suggests that long-term treatment of linagliptin safely improves arterial function and inhibits progression of wall thickness independent of reversal for diabetic status, which may have beneficial potentials for residual risk management of atherosclerosis in type-2 diabetics receiving statin.