Lilly Insulin Glargine Versus Lantus® in Insulin-Naïve and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5)

Abstract

Introduction: This 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).

Methods: ELEMENT 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).

Results: The 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).

Conclusion: Overall, 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 registration: ClinicalTrials.gov identifier, NCT02302716.

Funding: Eli Lilly and Company and Boehringer Ingelheim. Plain language summary available for this article.

Keywords: ELEMENT 5; Insulin glargine; LY2963016; Randomized controlled trial; Type 2 diabetes.

Figures

Fig. 1

a Change in glycated hemoglobin A1c (HbA1c) from baseline at 24 weeks, b HbA1c from baseline to 24 weeks, c 7-point self-monitored blood glucose (SMBG) at baseline and 24 weeks (reported as plasma-equivalent glucose values), d fasting plasma glucose (FPG) over 24 weeks. Data are shown as the least squares mean (LSM) with the standard error. Analyses are based on a mixed model repeated measures. CI Confidence interval, IGlar insulin glargine (Lantus), LSM Diff least squares mean difference, LY IGlar Lilly insulin glargine, PPG postprandial glucose. Asterisk indicates P< 0.05 for between-treatment difference

Fig. 2

Percentage binding of detectable anti-insulin glargine antibodies over 24 weeks (all patients with detectable antibodies). Data are shown as the median with the 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), LOCF Last observation carried forward, LY IGlar Lilly insulin glargine, n number of patients with detectable insulin antibodies