Dataset Information

In Silico Head-to-Head Comparison of Insulin Glargine 300?U/mL and Insulin Degludec 100?U/mL in Type 1 Diabetes.

ABSTRACT: Background: Second-generation long-acting insulin glargine 300?U/mL (Gla-300) and degludec 100?U/mL (Deg-100) provide novel basal insulin therapies for the treatment of type 1 diabetes (T1D). Both offer a flatter pharmacokinetic (PK) profile than the previous generation of long-acting insulins, thus improving glycemic control while reducing hypoglycemic events. This work describes an in silico head-to-head comparison of the two basal insulins on 24-h glucose profiles and was used to guide the design of a clinical trial. Materials and Methods: The Universities of Virginia (UVA)/Padova T1D simulator describes the intra-/interday variability of glucose-insulin dynamics and thus provides a robust bench-test for assessing glucose control for basal insulin therapies. A PK model describing subcutaneous absorption of Deg-100, in addition to the one already available for Gla-300, has been developed based on T1D clinical data and incorporated into the simulator. One hundred in silico T1D subjects received a basal insulin dose (Gla-300 or Deg-100) for 12 weeks (8 weeks uptitration, 4 weeks stable dosing) by morning or evening administration in a basal/bolus regimen. The virtual patients were uptitrated to their individual doses with two different titration rules. Results: The last 2-week simulated continuous glucose monitoring data were used to calculate various outcome metrics for both basal insulin treatments, with primary outcome being the percent time in glucose target (70-140?mg/dL). The simulations show no statistically significant difference for Gla-300 versus Deg-100 in the main endpoints. Conclusions: This work suggests comparable glucose control using either Gla-300 or Deg-100 and was used to guide the design of a clinical trial intended to compare second-generation long-acting insulin analogues.

SUBMITTER: Schiavon M

PROVIDER: S-EPMC7407002 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In Silico Head-to-Head Comparison of Insulin Glargine 300 U/mL and Insulin Degludec 100 U/mL in Type 1 Diabetes.

Schiavon Michele M Visentin Roberto R Giegerich Clemens C Sieber Jochen J Dalla Man Chiara C Cobelli Claudio C Klabunde Thomas T

Diabetes technology & therapeutics 20200325 8

Background: Second-generation long-acting insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) provide novel basal insulin therapies for the treatment of type 1 diabetes (T1D). Both offer a flatter pharmacokinetic (PK) profile than the previous generation of long-acting insulins, thus improving glycemic control while reducing hypoglycemic events. This work describes an in silico head-to-head comparison of the two basal insulins on 24-h glucose profiles and was ...[more]

PMID: 32125178

Similar Datasets

Project description:IntroductionSuboptimal glycaemic control among people with type 1 diabetes (T1D) is known to lead to long-term micro- and macrovascular complications and, unfortunately, it is still prevalent even in the most affluent societies. Although glycated haemoglobin monitoring is considered to be the gold standard for assessing glycaemic control, such monitoring is unable to reliably measure acute glycaemic excursions. Continuous glucose monitoring (CGM) has been shown to improve glucose control and reduce the incidence of hypoglycaemia, and also allow a more complete assessment of overall glycaemic control and hyper- and hypoglycaemic excursions. The use of CGM has led to time-in-range, which is the time that a patient is within the glycaemic range of 70 to 180 mg/dL, to be adopted as a treatment target. To date, only limited data comparing the second-generation insulins glargine 300 U/mL (Gla-300) and degludec 100 U/mL (IDeg-100) in people with T1D are available, and there is no CGM literature on comparisons of the use of CGM results to assess primary, secondary and tertiary endpoints. The aim of the InRange study was to address this unmet need.MethodsInRange is a multicentre, randomised, active-controlled, parallel-group, 12-week, open-label, phase 4, comparative study. Adults with T1D will be randomised to receive once-daily Gla-300 or IDeg-100 by subcutaneous injection in the morning. Following an 8-week titration period, CGM data will be collected over 20 consecutive days.Planned outcomesThe primary objective is to demonstrate that Gla-300 is noninferior to IDeg-100 in terms of glycaemic control [time-in-range ≥ 70 to ≤ 180 mg/dL (≥ 3.9 to ≤ 10 mmol/L)] and variability, as assessed using CGM, in adults with T1D. The results are expected to help confirm the utility of CGM in clinical practice in this population and provide insight into its application as an outcome measure in clinical practice.Trial registrationNCT04075513.

Project description:IntroductionFollowing pivotal trials, real-world evidence is important to assess the impact of new drugs in everyday clinical practice. The RESTORE-1 study aimed to compare effectiveness and safety of the second-generation basal insulins (2BI), i.e., insulin glargine 300 U/ml (Gla-300) vs. degludec 100 U/ml (IDeg-100), in type 1 diabetes (T1D).MethodsRetrospective, non-inferiority, multicenter study, based on electronic medical records. All patients switching to Gla-300 or IDeg-100 from first-generation basal insulins (1BI) were 1:1 propensity score matched (PSM). Changes during 6 months in HbA1c (primary endpoint), fasting plasma glucose (FPG), body weight, and insulin doses were assessed using linear mixed models for repeated measures. Incidence rates (IR) of hypoglycemic events were assessed.ResultsOverall, 19 centers provided data on 585 patients in each PSM cohort. For both groups, statistically significant reductions in HbA1c from baseline to 6 months were documented: - 0.20%; (95% CI - 0.32; - 0.08) in the Gla-300 group and - 0.14%; (95% CI - 0.24; - 0.04) in the IDeg-100 group. The non-inferiority of Gla-300 vs. IDeg-100 was confirmed (non-inferiority margin of 0.30%; upper 95% CI at 6 months, 0.09%). No statistically significant between-group differences emerged in FPG and body weight. Dose changes of basal and short-acting insulin were small in both groups, but higher in the Gla-300 group than in the Deg-100 group (p < 0.006). Incidence rates (IR) of hypoglycemia (blood glucose ≤ 70 mg/dl and < 54 mg/dl) during the 6-month follow-up by treatment were slightly lower in the Gla-300 group than in the Deg-100 group [IR ratios 0.82 (95% CI 0.55; 1.22) and 0.83; (95% CI 0.38; 1.83), respectively]. Hypoglycemic events (blood glucose < 54 mg/dl) decreased at 6 months in both groups (p = 0.01 for Gla-300 and p < 0.001 for IDeg-100). There were no severe hypoglycemic events for Gla-300 and seven events for IDeg-100 (p = 0.02).ConclusionsSwitching from 1BI to 2BI in adults with T1D was associated with similar improvements in glycemic control and overall significant decrease in hypoglycemia, with no severe events with Gla-300. Effectiveness of both insulins was limited by under-titration.

Dataset Information

In Silico Head-to-Head Comparison of Insulin Glargine 300?U/mL and Insulin Degludec 100?U/mL in Type 1 Diabetes.

Publications

<i>In Silico</i> Head-to-Head Comparison of Insulin Glargine 300 U/mL and Insulin Degludec 100 U/mL in Type 1 Diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure