Dataset Information

Duration of action of two insulin glargine products, LY2963016 insulin glargine and Lantus insulin glargine, in subjects with type 1 diabetes mellitus.

ABSTRACT:

Aims

LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products manufactured by distinct processes, but with identical amino acid sequences. This study compared the duration of action of LY IGlar and IGlar in subjects with type 1 diabetes mellitus (T1DM).

Materials and methods

This was a randomized, double-blind, single-dose, two-period, crossover study. Twenty subjects underwent 42-hour euglycaemic clamps after a single subcutaneous 0.3-U/kg dose of LY IGlar or IGlar. In this study, the duration of action was defined as the time required for blood glucose levels to rise consistently above a predefined cut-off of 8.3 mmol/L (150 mg/dL) from a state of euglycaemia. Blood samples were collected to measure blood glucose for pharmacodynamic (PD) evaluations.

Results

End of action was reached within 42 hours in 26 of 40 clamps (13 LY IGlar and 13 IGlar). The median duration of action for all subjects was 37.1 and 40.0 hours, and the mean duration of action (calculated using only patients who reached end of action) was 23.8 and 25.5 hours for LY IGlar and IGlar, respectively. The duration of action was demonstrated to be similar between the treatments using time-to-event analysis (log-rank test of equality p = .859). Following administration of LY IGlar and IGlar, the PD parameters of maximum glucose infusion rate (R _max ) and total glucose infusion during the clamp (G _tot ) were comparable.

Conclusion

LY IGlar and IGlar had similar duration of action and comparable PD parameters in subjects with T1DM.

SUBMITTER: Linnebjerg H

PROVIDER: S-EPMC5215447 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Duration of action of two insulin glargine products, LY2963016 insulin glargine and Lantus insulin glargine, in subjects with type 1 diabetes mellitus.

Linnebjerg Helle H Lam Eric Chen Quin EC Zhang Xin X Seger Mary E ME Coutant David D Chua Laiyi L Kapitza Christoph C Heise Tim T

Diabetes, obesity & metabolism 20160908 1

<h4>Aims</h4>LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products manufactured by distinct processes, but with identical amino acid sequences. This study compared the duration of action of LY IGlar and IGlar in subjects with type 1 diabetes mellitus (T1DM).<h4>Materials and methods</h4>This was a randomized, double-blind, single-dose, two-period, crossover study. Twenty subjects underwent 42-hour euglycaemic clamps after a single subcutaneous 0.3-U/kg dose of LY IGlar or IGlar. ...[more]

PMID: 27484286

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Project description:Background: This study investigated the effectiveness and safety of switching from Basalin® to Lantus® in Chinese patients with diabetes mellitus (DM). Methods: A retrospective chart review conducted using the electronic medical records of patients hospitalized at the Qingdao Endocrine and Diabetes Hospital from 2005 to 2016. All patients were diagnosed with DM and underwent switching of insulin from Basalin to Lantus during hospitalization. Data collected included fasting (FBG), pre- and post-prandial whole blood glucose, insulin dose, reasons for insulin switching and hypoglycemia. Four study time points were defined as: hospital admission, Basalin initiation, insulin switching (date of final dose of Basalin), and hospital discharge. Blood glucose measurements were imputed as the values recorded closest to the dates of these four time points for each patient. Results: Data from 73 patients (70 patients with type 2 diabetes, 2 with type 1, and 1 undisclosed) were analyzed. At admission, mean glycated hemoglobin (HbA1c) and FBG were 8.9% (SD=1.75) and 9.98 (3.22) mmol/L, respectively. Between Basalin initiation and insulin switch, mean FBG decreased from 9.68 mmol/L to 8.03 mmol/L (p<0.0001), over a mean 10.8 (SD=6.85) days of Basalin treatment, and reduced further to 7.30 mmol/L at discharge (p=0.0116) following a mean 6.6 (7.36) days of Lantus. The final doses of Basalin and Lantus were similar (0.23 vs. 0.24 IU/kg/day; p=0.2409). Furthermore, reductions in pre- and post-prandial blood glucose were also observed between Basalin initiation, insulin switch and hospital discharge. The incidence of confirmed hypoglycemia was low during Basalin (2 [2.4%]) and Lantus (1 [1.2%]) treatment, with no cases of severe hypoglycemia. Conclusion: In this study population, switching from Basalin to Lantus was associated with further reductions in blood glucose, although the dose of insulin glargine did not increase. Further studies are required to verify these findings and determine the reason for this phenomenon.

Project description:BackgroundChronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.ObjectivesTo assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.Search strategyWe searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.Selection criteriaAll randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.Data collection and analysisTwo authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.Main resultsThis review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.Authors' conclusionsOur analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

Project description:Background and objectivesLilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®) are basal insulin glargine analogs with identical amino acid sequence and similar pharmacological profiles. ELEMENT 5, a Phase 3, prospective, randomized, multinational, two-arm, active-controlled, open-label, parallel-design study in type 2 diabetes mellitus (T2DM) patients (N = 493) showed similar efficacy and safety profiles with LY IGlar and IGlar. This study reports results from India (N = 100) and East Asia (N = 134) subpopulations.MethodsPatients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24.ResultsWithin-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: - 0.83%; IGlar: - 0.62%; difference [95% CI] - 0.21 [- 0.70, 0.28]) and East Asia (LY IGlar: - 1.28%; IGlar: - 1.26%; difference [95% CI] - 0.02 [- 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002).ConclusionEfficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population.Clinical trial registrationNCT02302716.

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Dataset Information

Duration of action of two insulin glargine products, LY2963016 insulin glargine and Lantus insulin glargine, in subjects with type 1 diabetes mellitus.

Aims

Materials and methods

Results

Conclusion

Publications

Duration of action of two insulin glargine products, LY2963016 insulin glargine and Lantus insulin glargine, in subjects with type 1 diabetes mellitus.

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