title: Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial.
abstract: BACKGROUND
  Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes.
  
  
  METHODS
  We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers.
  
  
  RESULTS
  The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups.
  
  
  CONCLUSIONS
  Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes.
  
  
  BACKGROUND
  Registered at http://www.umin.ac.jp under UMIN000003784.
authors.affiliation: Center of Ultrasonic Diagnostics, Okayama University Hospital, Okayama, Japan. hirokioe@gmail.com.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oe
authors.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. ichibun@cc.okayama-u.ac.jp.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Internal Medicine, Kihara Cardiovascular Clinic, Asahikawa, Japan. kiharah@potato.hokkai.net.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kihara
authors.affiliation: Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan. shimadak@med.osaka-cu.ac.jp.
authors.forename: Kenei
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan. shota0022@gmail.com.
authors.forename: Shota
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Takagi Cardiology Clinic, Kyoto, Japan. tcardiol@qb4.so-net.ne.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. miyoshit@cc.okayama-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Miyoshi
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan. hirata8080@gmail.com.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, Japan. yoshikawaj@n-watanabe-hosp.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshikawa
authors.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. itomd@md.okayama-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003971:Diastole; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004452:Echocardiography; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D065089:Glycoside Hydrolase Inhibitors; D007294:Inositol; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human; C102817:voglibose