title: Cotreatment with the α-glucosidase inhibitor miglitol and DPP-4 inhibitor sitagliptin improves glycemic control and reduces the expressions of CVD risk factors in type 2 diabetic Japanese patients.
abstract: OBJECTIVE
  In this study, we examined whether inhibition of postprandial hyperglycemia by combination therapy with two drugs for reducing postprandial hyperglycemia, i.e., α-glucosidase inhibitor miglitol and dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin, improves glycemic control and reduces the risk of cardiovascular disease (CVD) development.
  
  
  METHODS
  We enrolled 32 type 2 diabetic Japanese patients with hemoglobin A1c (HbA1c) levels ranging from 6.9% to 10.5%, who had been treated for at least 2 months with 50mg miglitol (t.i.d.) or 50 mg sitagliptin (q.d.). Following a monotherapy period with either miglitol (Group-M) or sitagliptin (Group-S) for 1 month, the patients were subjected to combination therapy with sitagliptin and miglitol for 3 months. Meal tolerance tests were performed at the end of the monotherapy and combination therapy.
  
  
  RESULTS
  Combination therapy for 3 months after monotherapy reduced HbA1c (changes: Group-M: -1.3%±0.7%, P<0.001; Group-S: -0.6%±0.5%, P<0.001) and glycoalbumin levels and increased 1,5-anhydroglucitol concentrations in the blood. In the meal tolerance tests, circulating active glucagon-like peptide-1 levels were elevated in both groups, while active glucose-dependent insulinotropic polypeptide levels were reduced by combination therapy in the group with add-on miglitol therapy. The plasma protein concentrations of interleukin (IL)-8 and adhesion molecules (sE-selectin and sVCAM-1) were reduced by switching to the combination therapy, in particular with the add-on miglitol therapy.
  
  
  CONCLUSIONS
  Our results suggest that combination therapy with miglitol and sitagliptin improves glycemic control and reduces the circulating protein concentrations of IL-8, sE-selectin, and sVCAM-1 in type 2 diabetic Japanese patients.
authors.affiliation: Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, The University of Shizuoka, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Imai
authors.affiliation: Naka Kinen Clinic, Ibaraki 311-0113, Japan.
authors.forename: Miyoko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Mochizuki
authors.affiliation: Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd., Mie 511-0406, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fuchigami
authors.affiliation: Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, The University of Shizuoka, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. Electronic address: gouda@u-shizuoka-ken.ac.jp.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Goda
authors.affiliation: Naka Kinen Clinic, Ibaraki 311-0113, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Osonoi
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D054795:Incretins / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D019040:E-Selectin; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D016209:Interleukin-8; D011719:Pyrazines; D014230:Triazoles; D019010:Vascular Cell Adhesion Molecule-1; C045621:miglitol; D017485:1-Deoxynojirimycin; D000068900:Sitagliptin Phosphate
keywords: Adhesion molecule; CVD risk factor; Combination therapy; Inflammatory cytokine; Type 2 diabetes