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

• Published in: Metabolism, clinical and experimental Vol. 63; no. 6; pp. 746 - 753
• Main Authors: Imai, Chihiro, Saito, Miyoko, Mochizuki, Kazuki, Fuchigami, Masahiro, Goda, Toshinao, Osonoi, Takeshi
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2014; Elsevier
• Subjects: 1-Deoxynojirimycin - administration & dosage; 1-Deoxynojirimycin - analogs & derivatives; 1-Deoxynojirimycin - therapeutic use; Adhesion molecule; Adult; Aged; Asian Continental Ancestry Group; Biological and medical sciences; Biomarkers - blood; Blood Glucose - metabolism; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Combination therapy; CVD risk factor; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Drug Therapy, Combination; E-Selectin - blood; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Incretins - blood; Inflammatory cytokine; Interleukin-8 - blood; Japan; Male; Medical sciences; Middle Aged; Prospective Studies; Pyrazines - administration & dosage; Pyrazines - therapeutic use; Risk Factors; Sitagliptin Phosphate; Triazoles - administration & dosage; Triazoles - therapeutic use; Type 2 diabetes; Vascular Cell Adhesion Molecule-1 - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Japan; triglyceride; Type 2 diabetes; DPP; impaired glucose tolerance; GLP; Combination therapy; total cholesterol; TNF; glucose-dependent insulinotropic polypeptide; CVD risk factor; HDL-C; Inflammatory cytokine; von Willebrand factor; 1,5-anhydroglucitol; glucagon-like peptide; interleukin; HbA1c; cardiovascular disease; monocyte chemotactic protein; IL; ICAM; vWf; Adhesion molecule; GIP; high-density lipoprotein-cholesterol; TC; CVD; tPAI; total plasminogen activator inhibitor; VCAM; TG; dipeptidyl peptidase; tumor necrosis factor; IGT; 1,5-AG; MCP; vascular cell adhesion molecule; hemoglobin A1c; intercellular adhesion molecule; Dipeptidyl-peptidase IV; Endocrinopathy; Human; Enzyme; Miglitol; Enzyme inhibitor; Metabolic diseases; Sitagliptin; Gene expression; Japanese; Glycosylases; Peptidases; Hypoglycemic agent; α-Glucosidase; Gliptine derivatives; Glycosidases; Risk factor; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Endocrinology; Glycemia
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2013.12.014

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. Materials/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 50 mg 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.