sitagliptin-phosphate and mitiglinide

The combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a long-acting insulin analogue is widely used in clinical practice. However, some patients fail to achieve lower postprandial hyperglycemia. Mitiglinide, a short-acting insulinotropic sulfonylurea receptor ligand, is effective for postprandial hyperglycemia. Recently, it has been reported that the combination therapy of mitiglinide with a DPP-4 inhibitor could improve glycemic control. However, the efficacy of those under long-acting insulin analogue therapy remains to be investigated. Thus, we conducted a prospective single-center study of eight Japanese patients with type 2 diabetes mellitus receiving mitiglinide added to the combination therapy of sitagliptin and insulin glargine, and evaluated its efficacy and safety by continuous glucose monitoring (CGM). Participants' (four men and four women) mean age was 70.3 ± 10.6 years. Their mean body mass index, HbA1c level, and urinary C-peptide level were 22.0 ± 2.8 kg/m(2), 9.2 ± 1.2%, and 50.0 ± 31.4 μg/day, respectively. CGM showed that as compared with the combination of only sitagliptin and insulin glargine, mitiglinide in combination with sitagliptin and insulin glargine significantly reduced glycemic fluctuation indices, total area for the range of 24-h glycemic fluctuations (p = 0.04), mean amplitude of glycemic excursions (p = 0.03), and the proportion of time in hyperglycemia (p = 0.02) without significant difference in the proportion of time in hypoglycemia (p = 0.18). Hence, we have demonstrated the efficacy and safety of the add-on treatment with mitiglinide in type 2 diabetic patients, receiving the combination therapy of sitagliptin and insulin glargine.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Humans; Hyperglycemia; Insulin Glargine; Isoindoles; Male; Monitoring, Physiologic; Sitagliptin Phosphate

To compare the efficacy of mitiglinide and sitagliptin, alone or in combination, on postprandial excursion and glycemic variability assessed by continuous glucose monitoring (CGM) in a single-day treatment setting.. This was a post hoc analysis of a randomized crossover study comparing the efficacy of sitagliptin, mitiglinide and the combination of these two drugs. Twenty-four hour CGM was performed before and after a single-day treatment with each drug alone or in combination.. Mean glucose levels were decreased in all groups. The average of three postprandial glucose excursions AUC (average of all three 4-h postprandial periods throughout the day) (AUCpp-average) decreased in the mitiglinide and combination treatment groups, but not in the sitagliptin group. The lowering effect on AUCpp-average was greater in patients given mitiglinide (-47 mg/dl, p < 0.001) or combination treatment (-66 mg/dl, p < 0.001) compared with sitagliptin alone (-18 mg/dl). The reduction in mean amplitude of glycemic excursion was greater with mitiglinide (-29.3 mg/dl, p < 0.001) and combination treatment (-28.3 mg/dl, p < 0.01) than with sitagliptin alone (-8.9 mg/dl).. Mitiglinide or combination treatment resulted in lower glycemic variability and postprandial glucose excursion than sitagliptin alone; however, the results of this single-day pharmacodynamics study cannot be generalized to a clinical setting.

Topics: Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Isoindoles; Male; Middle Aged; Postprandial Period; Prospective Studies; Pyrazines; Sitagliptin Phosphate; Triazoles

Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life.. Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period.. The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period.. Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.

Topics: Acarbose; Aged; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Drug Substitution; Drug Therapy, Combination; Female; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Male; Middle Aged; Prospective Studies; Pyrazines; Serum Albumin; Sitagliptin Phosphate; Triazoles

To compare postprandial efficacy in type 2 diabetic patients given mitiglinide and sitagliptin, both of which are known to improve postprandial hyperglycemia, by using continuous glucose monitoring (CGM).. Eleven patients with type 2 diabetes were given mitiglinide 10 mg three times a daily or sitagliptin 50 mg once a day for 1 month and were hospitalized for 4 days and evaluated by CGM. On discharge, they were crossed over to the other regimen for 1 month of treatment/4 days of evaluation. The CGM data were used to compare each parameter for glycemic variability.. The patients were 60 ± 10 (mean ± SD) years old, and had HbA1c value 7.3 ± 0.9%. The pre-meal glucose levels before lunch were significantly lower with mitiglinide than with sitagliptin (116 ± 26/131 ± 34 mg/dl, p = 0.022). The AUC measuring over 140 mg/dl 3 h after breakfast (mitiglinide 4812 ± 4219/sitagliptin 7807 ± 6391 mg/dl·min, p = 0.042) and lunch (mitiglinide 5658 ± 5856/sitagliptin 8492 ± 7161, p = 0.050) was significantly lower with mitiglinide than with sitagliptin.. A CGM-based comparison showed that mitiglinide and sitagliptin were different in their glucose-lowering effects, where mitiglinide significantly improved hyperglycemia after breakfast and lunch, and significantly lowered pre-meal glucose levels before lunch, compared to sitagliptin.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Isoindoles; Middle Aged; Pilot Projects; Postprandial Period; Pyrazines; Sitagliptin Phosphate; Triazoles

The postprandial glucose (PPG) level is reduced by α-GIs, glinides and DPP4Is through different pharmacological actions. The aim of this study was to compare the effect of sitagliptin (S) versus that of the combination of mitiglinide and voglibose (M+V) on markers of glycemic control.. A randomized cross-over trial was performed in 20 patients with drug-naïve type 2 diabetes. The patients were randomized to receive S (50 mg/day) or M+V (1 tablet 3 times daily). Treatment was continued for 8 weeks, after which they were switched to the other regimen and treated for another 8 weeks. At baseline, after the first regimen, and after the second regimen, a meal test was performed.. The markers of glycemic control were examined.. Reduction of glucose excursion was significantly greater with M+V than with S. HbA1c did not change with either regimen. However, 1,5-anhydroglucitol showed a significant increase from baseline with both regimens (7.9 ± 4.3 μg/ml at baseline vs. 10.6 ± 5.5 with S, p < 0.05 and 15.1 ± 6.2 with M+V, p < 0.01). Compared with baseline, glycoalbumin was significantly reduced by M+V, but not S (19.6 ± 2.9% at baseline vs. 17.3 ± 3.8% with M+V, p < 0.05).. M+V achieved better control of PPG excursion than S.

Topics: Aged; Asian People; Blood Glucose; Cross-Over Studies; Deoxyglucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Inositol; Insulin; Isoindoles; Male; Middle Aged; Pyrazines; Serum Albumin; Sitagliptin Phosphate; Triazoles

The aim of this research was to compare the pharmacodynamics of the combination of mitiglinide and sitagliptin to that of each agent alone in Korean patients with type 2 diabetes mellitus (T2DM).. Patients with T2DM received mitiglinide alone, sitagliptin alone, or both drugs together in randomized sequence. A meal tolerance test (MTT) was conducted for each group, and plasma concentrations of glucose, insulin, C-peptide, glucagon, and intact glucagon-like peptide-1, and dipeptidyl peptidase-4 activity were measured from 2 h before breakfast through 4 h after breakfast on day 0 (pretreatment) and day 1 (posttreatment) of each treatment period. Integrated values of these pharmacodynamic variables were analyzed for changes from pretreatment to posttreatment and for differences between the three treatment groups.. Twenty-six patients with glycated hemoglobin A1c level of 7.4% ± 0.6%, fasting plasma glucose concentration of 141 ± 22 mg/dL, postprandial plasma glucose (PPG) concentration of 264 ± 48 mg/dL 1 h after the MTT, and diabetes duration of 3.0 ± 3.1 years (mean ± SD) were included in the study. Compared with mitiglinide or sitagliptin alone, the combination treatment lowered PPG additively (P < 0.001 vs. mitiglinide or sitagliptin alone) and the insulin secretory response (P = 0.03 vs. mitiglinide or sitagliptin alone). The integrated insulin concentrations changed significantly from before to after treatment (P < 0.01), but the change did not differ between the combination and mitiglinide groups. The insulinogenic index increased significantly after the combination treatment (P < 0.001 vs. mitiglinide or sitagliptin alone). The combination of mitiglinide and sitagliptin was generally well tolerated, with no hypoglycemic events.. The combination of mitiglinide and sitagliptin did not trigger hypoglycemia and controlled postprandial glucose excursion more effectively compared with either drug alone.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Confidence Intervals; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Isoindoles; Male; Middle Aged; Postprandial Period; Prospective Studies; Pyrazines; Reference Values; Severity of Illness Index; Sitagliptin Phosphate; Treatment Outcome; Triazoles

We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Synergism; Glucose Tolerance Test; Glyburide; Isoindoles; Male; Rats; Sitagliptin Phosphate