Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin

• Published in: Peptides (New York, N.Y. : 1980) Vol. 86; pp. 118 - 125
• Main Authors: Osonoi, Takeshi, Saito, Miyoko, Hariya, Natsuyo, Goto, Moritaka, Mochizuki, Kazuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016
• Subjects: 1-Deoxynojirimycin - analogs & derivatives; 1-Deoxynojirimycin - pharmacology; 1-Deoxynojirimycin - therapeutic use; Aged; alpha; Blood Glucose; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; DPP-4I; Drug Therapy, Combination; Female; Gastric Inhibitory Polypeptide - blood; GLP-1; Glucagon-Like Peptide 1 - blood; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Leptin - blood; Male; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Middle Aged; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Treatment Outcome; Type-2 diabetes mellitus; T2DM; RCT; LDL-C; DPP-4; ICBS; FBG; CoV; MTT; AUC; α-GI; HDL-C; SD; DBP; ANOVA; alpha; GA; BIA; HbA1c; BMI; SBP; GLP-1; SUD; Type-2 diabetes mellitus; DPP-4I; GIP; TC; CVD; TG; Metformin; ELISA
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2016.10.011

•Add-on therapy with anagliptin improves glycemic control in T2DM patients.•Add-on therapy with anagliptin increases GLP-1/GIP ratio in T2DM patients.•Add-on therapy with anagliptin did not induce weight gain in T2DM patients.•Add-on therapy with anagliptin reduces leptin concentration in T2DM patients. Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin. Forty-two Japanese T2DM patients with inadequately controlled disease (HbA1c: 6.5%–8.0%) treated with metformin (n=14), miglitol (n=14) or a combination of the two drugs (n=14) received additional treatment with anagliptin (100mg, p.o., b.i.d.) for 52 weeks. We assessed glycemic control, postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of leptin in those patients. Add-on therapy with anagliptin for 52 weeks improved glycemic control and increased the area under the curve of biologically active GLP-1 concentration without altering obesity indicators. Total GIP concentration at 52 weeks was reduced by add-on therapy in groups treated with miglitol compared with those treated with metformin. Add-on therapy reduced leptin concentrations. Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration.