Additive Effects of Miglitol and Anagliptin on Insulin-Treated Type 2 Diabetes Mellitus: A Case Study

Abstract

The aim of this case study was to examine the efficacy of a dipeptidyl peptidase-4 inhibitor (anagliptin) and an α-glucosidase inhibitor (miglitol) when added to ongoing insulin treatment in patients with type 2 diabetes mellitus. Continuous glucose monitoring was performed in four Japanese insulin-treated inpatients with type 2 diabetes. Baseline data were collected on day 1. Miglitol was administered on days 2 and 3. On day 4, miglitol and anagliptin were coadministered before breakfast. On days 1, 3, and 5, blood was drawn for plasma glucose, serum C-peptide, plasma glucagon, total and active glucagon-like peptide-1 (GLP-1), and total and active glucose-dependent insulinotropic peptide (GIP) measurements. Coadministration of anagliptin with miglitol resulted in additional improvements in glycemic control over the entire day in three of the four patients. The C-peptide, glucagon, and total and active GLP-1 and GIP responded differently to the medications for each patient, suggesting interindividual differences in hormonal responses, which may be complicated by multifactorial effects.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-014-0260-8) contains supplementary material, which is available to authorized users.

Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

“…Also, metformin has been proposed to increase GLP-1 secretion via modulation of bile acids [35]; inhibitory effect of metformin on bile acid reabsorption increases the luminal concentration of bile acids and stimulates Takeda G-protein receptor 5 (TGR5) on enteroendocrine L-cells, leading to increased GLP-1 secretion. Previous studies with a small number of participants have demonstrated insignificant changes in glucagon secretion after short-term treatment of α-glucosidase inhibitors [28293036]. However, in our study, the glucagon levels were suppressed after acarbose add-on therapy in the Met+Sita+Acarb group.…”

“…A single administration or a 2-week treatment of acarbose failed to demonstrate significant changes in the plasma glucagon level during MTT in the subjects with T2DM [2829]. In a report by Kishimoto and Noda [30], the short-term co-administration of α-glucosidase inhibitor (miglitol) and DPP4-inhibitor (anagliptin) showed a tendency for suppressed glucagon secretion in four patients. Theoretically, GLP-1 reduces glucose levels through its potent insulinotropic action as well as by suppressing glucagon secretion [31].…”

Comparative Analysis of the Bonding Modes between Two Antidiabetic Drugs with beta-Glucosidases from Different Species

“…For example, H4 changed its position nearly 90°, which lead to three H-bonds interactions between H4, O4 and Gln45, Tyr452 and His148 (Table 4). Actually, multiple hydroxyl groups played a critical role in the stabilization of the miglitol at the catalytic sites of β-glucosidases [46][47][48][49] .…”