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PLoS Med. 2016 Jun 28;13(6):e1002051. doi: 10.1371/journal.pmed.1002051. eCollection 2016 Jun.

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

Author information

1
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
2
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
3
Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan.
4
Department of Clinical Laboratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
5
Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan.
6
Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
7
Division of Cardiology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
8
Department of Cardiovascular Internal Medicine, Tosei General Hospital, Seto, Japan.
9
Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, Nishinomiya, Japan.
10
Department of Cardiology, Hiroshima City Hospital, Hiroshima, Japan.
11
Cardiovascular Center, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
12
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
13
Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
14
Department of Cardiology, Tokyo Medical University, Tokyo, Japan.
15
Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
16
Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
17
Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
18
Diabetes Therapeutics and Research Center, Tokushima University, Tokushima, Japan.
19
Department of Cardiology, Nagoya University Graduate School of Medicine and National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
20
Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.
21
Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan.
22
Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan.

Abstract

BACKGROUND:

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.

CONCLUSIONS:

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.

TRIAL REGISTRATION:

University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.

PMID:
27351380
PMCID:
PMC4924847
DOI:
10.1371/journal.pmed.1002051
[Indexed for MEDLINE]
Free PMC Article

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