A pilot study of the efficacy of miglitol and sitagliptin for type 2diabetes with a continuous glucose monitoring system and incretin-related markers

Abstract

BackgroundGlucose fluctuations including robust postprandial hyperglycemia are a risk for promoting atherosclerosis and diabetic complications. The α-glucosidase inhibitors and the dipeptidyl peptidase-4 (DPP-4) inhibitors have been found to effectively decrease postprandial hyperglycemia independently. Therefore, glycemic control with the combination of these drugs is warranted.MethodsContinuous glucose monitoring (CGM) was performed for 3 patients with type 2 diabetes and 1 control subject from the beginning to the end of the study. Medications were not administered to any of the subjects on the first day of the study. From the second day to the end of study (days 2-5), the subjects received miglitol (150 mg per day) and on days 4 and 5, sitagliptin (50 mg per day) was added to the treatment regimen. On the first, third, and fifth days of the study, blood was drawn at 0, 30, 60, 120, 180, and 240 min after breakfast for measurements of serum insulin, 1,5-anhydroglucitol (1,5-AG), plasma glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP).ResultsMeasurements of CGM and 1,5-AG levels showed that miglitol attenuated the escalation and fluctuation of glucose levels, and this was even more pronounced with the combination of miglitol and sitagliptin. The patterns of insulin secretion and glucagon secretion with miglitol alone or with a combination of miglitol and sitagliptin were various in the study subjects. Miglitol alone enhanced the release of GLP-1 in 1 patient with type 2 diabetes and the control subject, whereas the combination of miglitol and sitagliptin increased GLP-1 levels to varying degrees in all the subjects. Except for 1 subject, none of the subjects showed any change in GIP levels after the addition of sitagliptin, compared to the administration of miglitol alone.ConclusionsIn conclusion, CGM measurements revealed that a combination of the α-GI miglitol and the DPP-4 inhibitor sitagliptin effectively reduced postprandial glucose fluctuation and stabilized blood glucose levels. Completely different response patterns of insulin, glucagon, GLP-1, and GIP were observed among the study subjects with either medication alone or in combination, suggesting that individual hormone-dependent glycemic responses to the α-GI and DPP-4 inhibitors are complicated and multifactorial.

Effect of the Addition of Sitagliptin and Miglitol on Insulin-Treated Type 2 Diabetes

“…These effects were demonstrated precisely by the mean ± SD values and calculated AUC values of the glucose levels monitored by CGMS. The authors have previously shown that the combination of sitagliptin and miglitol was effective for reducing glucose fluctuations and stabilizing postprandial blood glucose levels in patients with type 2 diabetes receiving oral medication [19]. In the present study, the authors have demonstrated that both single administration and coadministration of these two drugs was also effective in an insulin-treated patient.…”

Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin

“…There are several papers reporting the additive use of DPP-4 inhibitors in cases in which α-glucosidase inhibitors proved incomplete control, analyzing combined effects of these drugs by CGM or incretin assays [17][18][19][20]. However, only few reports are available analyzing whether the additional use of α-glucosidase inhibitors provides beneficial effect on the blood glucose fluctuation and incretin hormone secretion in cases in which DPP-4 inhibitors were not sufficiently effective.…”

Concurrent Therapy with a Low-carbohydrate Diet and Miglitol Remarkably Improved the Postprandial Blood Glucose and Insulin Levels in a Patient with Reactive Hypoglycemia due to Late Dumping Syndrome

“…Several reports have been published regarding the usefulness of a low-carbohydrate diet and α-GI for late dumping syndrome (6)(7)(8)(9)(10)(11). Among these, four using CGM revealed that a low-carbohydrate diet and α-GI effectively decreased the frequency of hypoglycemia and the fluctuation of blood glucose after gastric surgery (5)(6)(7)11).…”

“…Among these, four using CGM revealed that a low-carbohydrate diet and α-GI effectively decreased the frequency of hypoglycemia and the fluctuation of blood glucose after gastric surgery (5)(6)(7)11). On the other hand, there is a report that miglitol was effective for reactive hypoglycemia secondary to late dumping syndrome, but not acarbose and voglibose (8).…”

“…After oral administration, acarbose and voglibose are not well absorbed. In contrast, miglitol presents at a high concentration in the upper small intestine and is subsequently absorbed at this site (11)(12)(13)(14). Such differences in pharmacokinetics could contribute to the superior therapeutic benefit of miglitol compared with voglibose; that is, it can suppress the postprandial blood glucose elevation and insulin secretion most effectively.…”