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Lilly Insulin Glargine Versus Lantus® in Type 2 Diabetes Mellitus Patients: India and East Asia Subpopulation Analyses of the ELEMENT 5 Study.

ABSTRACT: BACKGROUND AND OBJECTIVES:Lilly 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. METHODS:Patients 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. RESULTS:Within-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). CONCLUSION:Efficacy 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 REGISTRATION:NCT02302716.

SUBMITTER: Mohan V

PROVIDER: S-EPMC6656918 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThis study compared the efficacy and safety of similar U-100 insulin glargine products, namely, Lilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®), used once daily in combination with oral antihyperglycemic medications (OAMs) in adults with type 2 diabetes (T2D).MethodsELEMENT 5 was a phase III, randomized, multinational, open-label, treat-to-target, 24-week trial. Participants were insulin naïve (glycated hemoglobin [HbA1c] ≥ 7.0% to ≤ 11.0%) or on basal insulin (IGlar, neutral protamine Hagedorn or insulin detemir; HbA1c ≤ 11.0%) and taking ≥ 2 OAMs. The primary objective was to show that LY IGlar is noninferior to IGlar in terms of HbA1c reduction (0.4% noninferiority margin).ResultsThe study population (N = 493) was predominantly Asian (48%) or White (46%), with similar baseline characteristics between arms (P > 0.05). At 24 weeks, LY IGlar was noninferior to IGlar in terms of change in HbA1c level from baseline (- 1.25 vs. - 1.22%, respectively; least squares mean difference - 0.04%; 95% confidence interval - 0.22%, 0.15%). Other 24-week efficacy and safety results were also similar between treatments (P > 0.05), including insulin dose; percentage of patients having HbA1c of < 7% and ≤ 6.5%; overall rate and incidence of total, nocturnal, and severe hypoglycemia; adverse events; insulin antibody response; and weight gain. Daily mean 7-point self-monitored blood glucose reduction was similar between treatments at 24 weeks, with no differences at any time point except premorning-meal (fasting) blood glucose (LY IGlar - 2.37 mmol/L; IGlar - 2.69 mmol/L; P = 0.007).ConclusionOverall, LY IGlar and IGlar combined with OAMs provided similar glucose control and safety findings in this T2D population, which included a greater proportion of Asian patients and had broader background basal insulin experience than a previously studied T2D population.Trial registrationClinicalTrials.gov identifier, NCT02302716.FundingEli Lilly and Company and Boehringer Ingelheim. Plain language summary available for this article.

Project description:Insulin glargine is a long-acting insulin analog, which plays an important role in the treatment of diabetes mellitus. Biosimilar products of insulin glargine can provide patients with additional safe, high-quality, and potentially cost-effective options for treating diabetes. This article presents a randomized, double-blind, single-dose, two-treatment, four-period, replicate crossover, euglycemic clamp study which was designed to evaluate the PK and PD similarity between the recombinant insulin glargine developed by Wanbang (test) and Lantus® (reference) in healthy volunteers. Subjects received subcutaneous administration of the insulin glargine formulation (0.4 U/kg) on two occasions for the test and reference drug, respectively, and a 20% dextrose solution was infused at variable rate to clamp the blood glucose concentrations at 0.3 mmol/L below the subjects' fasting glucose for 24 h. Taking advantage of the improved sensitivity of the bioanalytical method applied and the solution of the matrix stability problem, the parent insulin glargine was determined in the vast majority of plasma samples using a fully validated UHPLC-MS/MS method. The PK characteristics of the parent insulin glargine were revealed for the first time: after subcutaneous injection, concentrations of the parent insulin glargine increased to a relative high level within 3 h, and then, a relatively flat concentration-time profile lasting for at least 12 h post-dose was observed. For the first time, the pharmacokinetic parameters of the parent insulin glargine were used as endpoints for similarity evaluation, which complied with the regulatory guidance better and made the similarity conclusion more powerful. The ratios of geometric means of all PK and PD endpoints were close to 100.00%. For the PK endpoints (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of the parent insulin glargine and its metabolite M1), the 90% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. For the PD endpoints [AUCGIR(0-24h), GIRmax, AUCGIR(0-12h), and AUCGIR(12-24h)], the 95% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. Based on the above mentioned results, it can be concluded that the PK and PD characteristics of the biosimilar drug developed by Wanbang are similar to those of Lantus.

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.

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Lilly Insulin Glargine Versus Lantus® in Type 2 Diabetes Mellitus Patients: India and East Asia Subpopulation Analyses of the ELEMENT 5 Study.

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