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

被引:57
作者
Oyama, Jun-ichi [1 ]
Murohara, Toyoaki [2 ]
Kitakaze, Masafumi [3 ]
Ishizu, Tomoko [4 ]
Sato, Yasunori [5 ]
Kitagawa, Kazuo [6 ]
Kamiya, Haruo [7 ]
Ajioka, Masayoshi [8 ]
Ishihara, Masaharu [9 ]
Dai, Kazuoki [10 ]
Nanasato, Mamoru [11 ]
Sata, Masataka [12 ]
Maemura, Koji [13 ]
Tomiyama, Hirofumi [14 ]
Higashi, Yukihito [15 ]
Kaku, Kohei [16 ]
Yamada, Hirotsugu [17 ]
Matsuhisa, Munehide [18 ]
Yamashita, Kentaro [19 ,20 ]
Bando, Yasuko K. [19 ,20 ]
Kashihara, Naoki [21 ]
Ueda, Shinichiro [22 ]
Inoue, Teruo [23 ]
Tanaka, Atsushi [1 ]
Node, Koichi [1 ]
机构
[1] Saga Univ, Dept Cardiovasc Med, Saga 840, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi 4648601, Japan
[3] Natl Cerebral & Cardiovasc Ctr, Dept Clin Med & Dev, Osaka, Japan
[4] Univ Tsukuba, Fac Med, Dept Clin Lab Med, Tsukuba, Ibaraki, Japan
[5] Chiba Univ, Grad Sch Med, Dept Global Clin Res, Chiba, Japan
[6] Tokyo Womens Med Univ, Dept Neurol, Tokyo, Japan
[7] Japanese Red Cross Nagoya Daiichi Hosp Nagoya Jap, Div Cardiol, Nagoya, Aichi, Japan
[8] Tosei Gen Hosp, Dept Cardiovasc Internal Med, Seto, Japan
[9] Hyogo Coll Med, Div Cardiovasc Med & Coronary Heart Dis, Nishinomiya, Hyogo 6638501, Japan
[10] Hiroshima City Hosp, Dept Cardiol, Hiroshima, Japan
[11] Japanese Red Cross Nagoya Daini Hosp, Cardiovasc Ctr, Nagoya, Aichi, Japan
[12] Univ Tokushima, Grad Sch, Inst Biomed Sci, Dept Cardiovasc Med, Tokushima 770, Japan
[13] Nagasaki Univ, Grad Sch Biomed Sci, Dept Cardiovasc Med, Nagasaki 852, Japan
[14] Tokyo Med Univ, Dept Cardiol, Tokyo 1608402, Japan
[15] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Cardiovasc Regenerat & Med, Hiroshima, Japan
[16] Kawasaki Med Sch, Dept Internal Med, Kurashiki, Okayama, Japan
[17] Tokushima Univ Hosp, Dept Cardiovasc Med, Tokushima, Japan
[18] Univ Tokushima, Diabet Therapeut & Res Ctr, Tokushima 770, Japan
[19] Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi 4648601, Japan
[20] Natl Hosp Org Nagoya Med Ctr, Nagoya, Aichi, Japan
[21] Kawasaki Med Sch, Dept Hypertens & Nephrol, Kurashiki, Okayama, Japan
[22] Univ Ryukyus, Dept Clin Pharmacol & Therapeut, Nishihara, Okinawa 90301, Japan
[23] Dokkyo Med Univ, Dept Cardiovasc Med, Mibu, Tochigi, Japan
关键词
INTIMA-MEDIA THICKNESS; GLUCAGON-LIKE PEPTIDE-1; CORONARY-HEART-DISEASE; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; ENDOTHELIAL FUNCTION; WALL THICKNESS; CARDIOVASCULAR EVENTS; GLYCEMIC CONTROL; RISK-FACTORS; TASK-FORCE;
D O I
10.1371/journal.pmed.1002051
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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