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.

Conflict of interest statement

Viswanathan Mohan and Manoj Chadha have received speaker fees from Eli Lilly and Company, Novo Nordisk and Sanofi. Young Min Cho has received research support or consultant fees from Astrazeneca, Sanofi, LG chemicals, and Hanmi. Sanjay Kalra has received speaker fees from Eli Lilly and Company, Novo Nordisk, and Sanofi. Rakesh Kumar Sahay has received speaker fees from Eli Lilly and Company, Novo Nordisk, and USV India. Indranil Bhattacharya, So Yeon Kim, and Erik Spaepen are employees of Eli Lilly and Company. Chien-Ning Huang, and Kyu Jeung Ahn do not have any conflict of interest.

Figures

Fig. 1

HbA1c levels over 24 weeks. a India subpopulation; b East Asia subpopulation; c ELEMENT 5 total population. Values presented are LSM (standard error). Analyses are based on mixed-model repeated-measures. Data points are slightly offset along the x axis to avoid overlapping error bars. HbA1c glycated hemoglobin, IGlar insulin glargine (Lantus), LSM least-square mean, LY IGlar Lilly insulin glargine. p > 0.05 for all comparisons between LY IGlar and IGlar in all three populations. p values were < 0.001 for all within-treatment comparisons in all three populations

Fig. 2

Self-monitored fasting blood glucose levels over 24 weeks. a India subpopulation; b East Asia subpopulation; c ELEMENT 5 total population. Values presented are LSM (standard error). Analyses are based on mixed-model repeated-measures. Data points are slightly offset along the x axis to avoid overlapping error bars. FBG fasting blood glucose, IGlar insulin glargine (Lantus), LSM least-squares mean, LY IGlar Lilly insulin glargine. p > 0.05 for all comparisons between LY IGlar and IGlar in all three populations except FBG for ELEMENT 5 total population (p = 0.007) and India (p = 0.002) at Week 24

Fig. 3

Incidence of hypoglycemia. a Total hypoglycemia; b Nocturnal hypoglycemia. Data presented are percentage of patients experiencing hypoglycemia measured for the overall 24-week treatment period. IGlar insulin glargine (Lantus), LY IGlar Lilly insulin glargine. p > 0.05 for all comparisons between LY IGlar and IGlar in all three populations

Fig. 4

Antibody binding levels over 24 weeks. a India subpopulation; b East Asia subpopulation; c ELEMENT 5 total population. Values are presented as median (25th, 75th percentiles). p values for treatment comparisons are derived from the Wilcoxon rank-sum test. Data points are slightly offset along the x axis to avoid overlapping error bars. IGlar insulin glargine (Lantus), LY IGlar Lilly insulin glargine. p > 0.05 for all comparisons between LY IGlar and IGlar in all three populations