Sitagliptin and Carotid Atherosclerosis in Type 2 Diabetes
Oyama, Jun-ichi Saga University
Murohara, Toyoaki Nagoya University
Kitakaze, Masafumi National Cerebral and Cardiovascular Center
Ishizu, Tomoko University of Tsukuba
Sato, Yasunori Chiba University
Kitagawa, Kazuo Tokyo Women’s Medical University
Kamiya, Haruo Japanese Red Cross Nagoya Daiichi Hospital
Ajioka, Masayoshi Tosei General Hospital
Ishihara, Masaharu Hyogo College of Medicine
Dai, Kazuoki Hiroshima City Hospital
Nanasato, Mamoru Japanese Red Cross Nagoya Daini Hospital
Maemura, Koji Nagasaki University
Tomiyama, Hirofumi Tokyo Medical University
Higashi, Yukihito Hiroshima University
Kaku, Kohei Kawasaki Medical School
Yamashita, Kentaro Nagoya University
Bando, Yasuko K. Nagoya University
Kashihara, Naoki Kawasaki Medical School
Ueda, Shinichiro University of the Ryukyus
Inoue, Teruo Dokkyo Medical University
Tanaka, Atsushi Saga University
Node, Koichi Saga University
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).
Methods and Findings
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.
© 2016 Oyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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