Effect of linagliptin on pulse wave velocity in early type 2 diabetes: A randomized, double‐blind, controlled 26‐week trial (RELEASE)

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2017-08, Vol.19 (8), p.1147-1154
• Main Authors: de Boer, Stefanie A., Heerspink, Hiddo J. L., Juárez Orozco, Luis E., van Roon, Arie M., Kamphuisen, Pieter W., Smit, Andries J., Slart, Riemer H. J. A., Lefrandt, Joop D., Mulder, Douwe J.
• Format: Article
• Language: English
• Subjects: antidiabetic drug; Antidiabetics; Aorta; Atherosclerosis - complications; Atherosclerosis - physiopathology; Atherosclerosis - prevention & control; Biomarkers - blood; Blood pressure; Blood Pressure - drug effects; cardiovascular disease; clinical trial; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetic Angiopathies - physiopathology; Diabetic Angiopathies - prevention & control; Dipeptidyl-peptidase IV; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Double-Blind Method; Double-blind studies; DPP‐4 inhibitor; Evidence-based medicine; Female; Follow-Up Studies; Glycated Hemoglobin A - analysis; Hemoglobin; Humans; Hyperglycemia - prevention & control; Hypertension - complications; Hypertension - prevention & control; Hypertriglyceridemia - complications; Hypertriglyceridemia - physiopathology; Hypertriglyceridemia - prevention & control; Hypoglycemia - chemically induced; Hypoglycemia - prevention & control; linagliptin; Linagliptin - adverse effects; Linagliptin - therapeutic use; Male; Middle Aged; Pulse Wave Analysis; Severity of Illness Index; type 2 diabetes; Vascular Stiffness - drug effects
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12925

Aims To evaluate the effects of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes. Methods A total of 45 people with type 2 diabetes (median [interquartile range] age 63 [54‐66] years, 61% men, mean ± standard deviation glycated haemoglobin [HbA1c] 6.3% ± 0.4% [45 ± 4.6 mmol/mol]), without cardiovascular disease and naïve to antidiabetic treatment, were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double‐blind fashion. PWV was assessed at baseline, 4 and 26 weeks of treatment, and again at 30, 4 weeks after treatment. The primary endpoint was between‐group difference in PWV (corrected for systolic blood pressure [SBP]) at week 26. Secondary endpoints included differences in central SBP and augmentation index (AIx). Results Compared with placebo, 26 weeks of linagliptin decreased PWV by an average of 0.91 m/s (95% confidence interval −1.76 to −0.06; P = .035). PWV returned to baseline after 4 weeks washout. Differences in central SBP and AIx were not different between linagliptin and placebo. Linagliptin decreased HbA1c (−0.4%; P