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

Abstract

Background: Glucose 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.

Methods: Continuous 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).

Results: Measurements 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.

Conclusions: In 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.

Figure 1

The results of CGM for patients in cases 1 to 3, and the control subject with the conditions of no medication, miglitol alone, and coadministration of miglitol and sitagliptin.

Figure 2

Time course of CGM measured glucose (A), insulin (B), I/G(insulin to CGM measured glucose ratio) (C), glucagon (D), active GLP-1 (E), and GIP (F) levels before and after meal intake in the patient in case 1. The clear squares indicate no medication, filled squares indicate miglitol administration, and filled triangles indicate coadministration of miglitol and sitagliptin.

Figure 3

Time course of CGM measured glucose (A), insulin (B), I/G(insulin to CGM measured glucose ratio) (C), glucagon (D), active GLP-1 (E), and GIP (F) levels before and after meal intake in the patient in case 2.

Figure 4

Time course of CGM measured glucose (A), insulin (B), I/G(insulin to CGM measured glucose ratio) (C), glucagon (D), active GLP-1 (E), and GIP (F) levels before and after meal intake in the patient in case 3.

Figure 5

Time course of CGM measured glucose (A), insulin (B), I/G(insulin to CGM measured glucose ratio) (C), glucagon (D), active GLP-1 (E), and GIP (F) levels before and after meal intake in the patient in the control subject.