Journal Article

The Effect of Sitagliptin on Carotid Artery Atherosclerosis in Type 2 Diabetes: The PROLOGUE Randomized Controlled Trial

Maemura, Koji, Bando, Yasuko K., Kitakaze, Masafumi, Nanasato, Mamoru, Kashihara, Naoki, Node, Koichi, Matsuhisa, Munehide, Ueda, Shinichiro, Inoue, Teruo, Sato, Yasunori, Kitagawa, Kazuo, Dai, Kazuoki, Higashi, Yukihito, Yamashita, Kentaro, Ishizu, Tomoko, Kamiya, Haruo, Kaku, Kohei, Ishihara, Masaharu, Ajioka, Masayoshi, Sata, Masataka, Tomiyama, Hirofumi, Oyama, Jun-ichi, Yamada, Hirotsugu, Murohara, Toyoaki, Tanaka, Atsushi

2016

Overview

Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM). We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged ≥30 y with T2DM (6.2% ≤ HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI -0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72% ± 0.05%, p = 0.008; group mean difference -0.159, 95% CI -0.278 to -0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation. In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment. University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Atherosclerosis / Atherosclerosis - drug therapy / Atherosclerosis - etiology / Biology and Life Sciences / Cardiovascular disease / Carotid arteries / Carotid Arteries - drug effects / Carotid Intima-Media Thickness / Clinical trials / Comparative analysis / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Diabetics / Dipeptidyl-Peptidase IV Inhibitors - pharmacology / Dipeptidyl-Peptidase IV Inhibitors - therapeutic use / Dosage and administration / Drug therapy / Female / Health aspects / Humans / Male / Medicine and Health Sciences / Middle Aged / Pharmaceutical industry / Prospective Studies / Research and Analysis Methods / Sitagliptin / Sitagliptin Phosphate - pharmacology / Sitagliptin Phosphate - therapeutic use / Studies