Insulin Degludec Requires Lower Bolus Insulin Doses Than Does Insulin Glargine in Japanese Diabetic Patients With Insulin-Dependent State

Abstract

Insulin degludec is a new-generation long-acting insulin analog that has stable and ultra-long glucose-lowering effects, as demonstrated using the euglycemic clamp technique.1,2 It has recently been approved for the treatment of diabetes in Europe and Japan. Insulin degludec is a soluble dihexamer preparation that forms stable soluble multihexamers after subcutaneous injection. These multihexamers are retained at the injection site for a short period of time before entering the blood stream in a slow and sustained manner by gradual dissolution with releasing monomers. They also bind with albumin via a fatty acid side chain at the injection site and in the blood, increasing the duration of the action. It has been reported that the frequency of nocturnal hypoglycemia was significantly lower in patients treated with insulin degludec than in patients treated with insulin glargine if overall glycemic control was equal.3-5 However, in the Food and Drug Administration review, 6 the advantageous effects of insulin degludec in nocturnal hypoglycemia were not apparent when patients with type 1 diabetes were analyzed alone or when the definition of the nighttime period was changed from 0:01-5:59 to 21:59-5:59 or to 0:01-7:59. Therefore, it is unclear whether insulin degludec is associated with a lower frequency of nocturnal hypoglycemia compared to insulin glargine. In addition, in a clamp study of The study presents a comparison of the glucose-lowering effects, glycemic variability, and insulin doses during treatment with insulin degludec or insulin glargine. Methods: In this open-label, single-center, 2-way crossover study, 13 Japanese diabetic outpatients in the insulin-dependent state on basal-bolus therapy were assigned to receive either insulin glargine followed by insulin degludec, or insulin degludec followed by insulin glargine. Basal insulin doses were fixed in principle, and patients self-adjusted their bolus insulin doses. Seventy-two-hour continuous glucose monitoring was performed 2 weeks after switching the basal insulin. Results: Mean blood glucose (mg/dL) was not significantly different between insulin degludec and insulin glargine over 48 hours (141.8 ± 35.2 vs 151.8 ± 43.3), at nighttime (125.6 ± 40.0 vs 124.7 ± 50.4), or at daytime (149.3 ± 37.1 vs 163.3 ± 44.5). The standard deviation (mg/dL) was also similar (for 48 hours: 48.9 ± 19.4 vs 50.3 ± 17.3; nighttime: 18.7 ± 14.3 vs 13.7 ± 6.7; daytime: 49.3 ± 20.0 vs 44.3 ± 17.7). Other indices of glycemic control, glycemic variability, and hypoglycemia were similar for both insulin analogs. Total daily insulin dose (TDD) and total daily bolus insulin dose (TDBD) were significantly lower with insulin degludec than with insulin glargine (TDD: 0.42 ± 0.20 vs 0.46 ± 0.22 U/ kg/day, P = .028; TDBD: 0.27 ± 0.13 vs 0.30 ± 0.14 U/kg/day, P = .036). Conclusions: Insulin degludec and insulin glargine provided effective and stable glycemic control. Insulin degludec required lower TDD and TDBD in this population of patients.

Adjustment of insulin doses when switching from glargine 100 U/ml or detemir to degludec: an observational study

“…These results confirm those reported in clinical trials and prospective observations [8-10, 13-15, 23, 24, 28]. In addition, a reduction of prandial insulin doses was observed after the switch, irrespective of the number of previous daily basal insulin injections [13,18,23]. Notably, the reduction of insulin doses occurred together with an improvement of glycemic control, as reported by some previous studies [13,23,28].…”

“…In several trials, degludec use was also associated with a lower dose of prandial insulin than comparators [6,7,9,10,14,15], although some studies failed to detect this difference [8]. In a 2-week crossover trial on a small sample of patients with type 1 diabetes, degludec was associated with a lower dose of prandial, but not basal, insulin when compared to glargine [18].…”

Is obesity associated with healing after non‐surgical periodontal therapy? A local vs. systemic evaluation

“…We observed a significant increase in HDL cholesterol (HDL‐C) levels after therapy in both periodontitis groups ( p = 0.03 in CPO and p < 0.001 in CPNW). Such an increase in HDL in response to periodontal therapy may lead to a decrease in cardiovascular risk in patients with periodontitis . We observed a greater increase in HDL‐C compared with that reported by Altay et al .…”

“…We observed a significant increase in HDL cholesterol (HDL-C) levels after therapy in both periodontitis groups (p = 0.03 in CPO and p < 0.001 in CPNW). Such an increase in HDL in response to periodontal therapy may lead to a decrease in cardiovascular risk in patients with periodontitis (26). We observed a greater increase in HDL-C compared with that reported by Altay et al; the difference may be due to differences in patient BMI (32.2 AE 5.2 in Altay et al vs. 36.26 AE 4.04 in the current study) in addition to the percentage of active local inflammation, as assessed by BOP (change from 53% to 24% in Altay et al and from 71% to 12% in the current study).…”

Switching from Twice-Daily Basal Insulin Injections to Once-Daily Insulin Degludec Injection for Basal-Bolus Insulin Regimen in Japanese Patients with Type 1 Diabetes: A Pilot Study

“…A few studies from Japan have already investigated the outcome of switching from once-daily or twice-daily basal insulin to once-daily insulin degludec in patients with type 1 diabetes [ 13 – 15 ]. Specifically, these studies investigated the effects of switching to insulin degludec in type 1 diabetes patients who were being treated with a combination of once- or twice-daily injections of insulin glargine or detemir, though there are no studies that focused on type 1 diabetes patients treated only with twice-daily basal insulin.…”