Switching from Insulin Degludec plus Dipeptidyl Peptidase-4 Inhibitor to Insulin Degludec/Liraglutide Improves Glycemic Variability in Patients with Type 2 Diabetes: A Preliminary Prospective Observation Study

Abstract

Incretins reduce glycemic variability (GV) in patients with type 2 diabetes, but it is unknown whether switching from a combination of basal insulin and a DPP-4 inhibitor to insulin degludec/liraglutide (IDegLira) improves GV. We performed an exploratory prospective observational study to compare the effect of IDegLira and the combination on GV. We recruited hospitalized patients with type 2 diabetes who had stable glycemic control with insulin degludec (≤16 units/day) and taking a DPP-4 inhibitor. GV was analyzed using continuous glucose monitoring (CGM) before and after switching the medication to IDegLira. The principal endpoint was the change in mean amplitude of glycemic excursions (MAGE). Other indices of GV and CGM parameters were analyzed as the secondary endpoints. Fifteen participants were enrolled and 12 completed the study. In these participants, the DPP-4 inhibitor and insulin degludec were discontinued, and the equivalent dose of IDegLira was commenced. Switching to IDegLira significantly improved MAGE from 74.9 (60.3, 97.7) mg/dL to 64.8 (52.0, 78.2) mg/dL (P < 0.05), as well as other indices of GV and 24-hour mean blood glucose concentration. Analysis of the ambulatory glucose profile showed marked reductions in postprandial glucose concentration. Nocturnal glucose concentration was similar under the two treatment regimens. IDegLira improved GV as well as the mean and the postprandial glucose concentration by switching from insulin degludec plus DPP-4 inhibitor combination. IDegLira might be beneficial for patients being treated with low-dose basal insulin.

Figure 1

Flowchart for the study. DPP-4i: dipeptidyl peptidase-4 inhibitor; IDegLira: insulin degludec/liraglutide.

Figure 2

Flow diagram of this study. In total, 75 patients with type 2 diabetes hospitalized during the study periods. Of these, 57 patients were excluded due to exclusion criteria. Fifteen patients were enrolled, and 3 patients dropped out. Finally, 12 patients completed the study. T2DM: type 2 diabetes; DPP-4 inhibitor: dipeptidyl peptidase-4 inhibitor; GLP-1RA: glucagon-like peptide-1 receptor agonist.

Figure 3

Mean amplitude of glycemic excursions before and after switching to insulin degludec/liraglutide. The figure was constructed for all 12 participants, and the error bars represent the standard deviation of measurements. All data was nonparametric and analyzed by Wilcoxon's signed-rank test. IDeg: insulin degludec; DPP-4i: dipeptidyl peptidase-4 inhibitor; IDegLira: insulin degludec/liraglutide. The error bars represent the standard deviation of measurements.

Figure 4

Ambulatory glucose profiles (AGPs). AGPs were constructed for all 12 participants. The black line represents the median glucose concentration, and the bands, which comprised small dots and larger dots, represent the 25th–75th and 10th–90th percentiles, respectively. The dotted line represents the target glucose range. (a) Combination therapy comprising a DPP-4 inhibitor and insulin degludec. (b) IDegLira. IDeg: insulin degludec; DPP-4i: dipeptidyl peptidase-4 inhibitor; IDegLira: insulin degludec/liraglutide.

Figure 5

Mean glucose concentrations during the phases of the day. The figure was constructed for all 12 participants, and the error bars represent the standard deviation of measurements. All data was parametric and analyzed by Student's t-test. The mean glucose concentrations are shown for the preprandial periods, postprandial periods, and overnight. The preprandial phase was defined as 60 minutes before the delivery of a meal and the postprandial phase as 180 minutes from the start of the meal. The nocturnal phase was defined as 03:00–06:00. Black diamond: insulin degludec plus a dipeptidyl peptidase-4 inhibitor; black circle, insulin degludec/liraglutide. ^∗∗P < 0.01; ^∗P < 0.05; NS: not significant.