Insulin Glargine Biosimilar Demonstrates Bioequivalence to Originator for Type 2 Diabetes

Elena Christofides, MD

Credit: Endocrinology Associates

Findings from a phase 3, multicenter, open-label, equivalence trial suggest similar immunogenicity, efficacy, and safety between originator insulin glargine (Lantus) and its proposed biosimilar (Basalin) in adult patients with type 2 diabetes.¹

Patients treated with the biosimilar experienced similar rates of positivity for treatment-induced glycated hemoglobin by week 26 versus those treated with the originator, including patients with and without previous insulin glargine exposure, and with a comparable frequency and nature of treatment-emergent adverse events.¹

“The emergence of biosimilar insulins offers a prospective path to reducing treatment expenses compared with the original insulin products while ensuring comparable efficacy and safety profiles,” Elena Christofides, MD, CEO of Endocrinology Research Associates, and colleagues wrote.¹ “The introduction of these biosimilars aims to alleviate the financial burden on both patients and health care systems while maintaining therapeutic efficacy and safety.”

According to the Centers for Disease Control and Prevention, about 38 million people in the US have diabetes, approximately 90-95% of whom have type 2 diabetes.² Insulin therapy is often an integral component of diabetes treatment to keep blood sugar under control and prevent diabetes complications, but access is frequently hindered by costly treatment expenses. Biosimilars offer a potential solution to these cost barriers with equivalent therapeutic efficacy and safety to the reference product.¹

To evaluate the immunogenicity, safety, and efficacy of reference glargine with that of a proposed biosimilar, investigators conducted a phase 3, multicenter, open-label, equivalence trial of 567 patients with type 2 diabetes seen at 57 sites and randomly assigned them in a 1:1 ratio to undergo treatment with either Lantus, the reference, or Basalin, the biosimilar, for 26 weeks. The primary endpoint was the proportion of participants who manifested treatment-induced anti-insulin antibodies, while secondary endpoints included efficacy and safety metrics, changes in glycated hemoglobin levels, and a comparative assessment of adverse events.¹

Participants who were already using insulin at the time of enrollment were required to continue their oral antidiabetic medications and substitute their basal insulin with the investigational product. Participants who were not using basal insulin at enrollment continued their oral antidiabetic medications, added the investigational product, and adjusted insulin dosing individually according to metabolic status. Investigators noted all participants underwent optimization and adjustments of insulin dosing as well as oral antidiabetic medication dosing as necessary.¹

Investigators randomly assigned 283 participants to the reference product and 284 to the biosimilar. A total of 515 (90.8%) participants completed the study, with similar percentages of participants in the biosimilar (91.2%) and the originator groups (90.5%).¹

Among the cohort, the mean age was 60.8 years, the mean weight was 98.1 kg (216.3 lbs), and most participants were male (60.1%) and White (79.7%). Demographic characteristics, including age, sex, ethnicity, and body mass index, were well-matched between the groups, and investigators pointed out the mean baseline level of HbA1c was also comparable between the treatment groups.¹

Investigators observed a similar proportion of participants who tested positive for treatment-induced anti-insulin antibodies in both the biosimilar (19.2%) and reference (21.3%) treatment groups (90% CI, -7.6% to 3.5%). Similar percentages of participants developed treatment-induced anti-insulin antibodies in each subgroup, including those with previous insulin glargine exposure (9.5% for biosimilar and 7.7% for reference) and those without previous insulin glargine exposure (20% for biosimilar and 21.9% for reference), indicating immunogenicity equivalence.¹

The majority of participants in both groups had a negative anti-insulin antibody status at baseline, and similar percentages of these participants exhibited newly confirmed anti-insulin antibody responses at week 26 (16.9% for biosimilar and 20.2% for reference). Additionally, at week 26, investigators observed a least squares mean difference of 0.06% in the change from baseline in HbA1c between the Basalin (-0.39%) and Lantus treatment groups (-0.45%), confirming their equivalence and the biosimilar’s non-inferiority based on predefined limits.¹

Investigators pointed out the percentage of participants who achieved fasting blood glucose levels of ≤8.0 mmol/L at week 26 was similar between the biosimilar and reference groups (46.8% and 48.8%, respectively), as was the percentage of participants who achieved HbA1c levels <7.0% (12.3% and 13.1%, respectively).¹

Of note, the frequency and nature of treatment-emergent adverse events reported during the study were consistent with expectations and generally similar between the groups (80.1% for biosimilar and 81.6% for reference). Hypoglycemia was the most commonly reported treatment-emergent adverse event, occurring in approximately half of the participants in each treatment group.¹

Investigators highlighted a single potential limitation to the study, citing its open-label design. However, to mitigate the risk of operational bias influencing the study outcomes, they noted certain roles within the sponsor and study team were maintained under blinding.¹

“The study affirms the bioequivalence of Basalin and Lantus in terms of immunogenicity, safety, and efficacy for adult patients with T2DM. Consistent with previous studies showing pharmacokinetic and pharmacodynamic bioequivalence in patients with T1DM, this study further substantiates the bioequivalence of Basalin to Lantus,” investigators concluded.¹

References:

1. ^{Christofides EA, Puente O, Norwood P, et al. Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study. Diabetes Obes Metab. 2024;1‐10. doi:10.1111/dom.1556010}
2. ^{US Centers for Disease Control and Prevention. Type 2 Diabetes. Diabetes. April 18, 2023. Accessed April 12, 2024. https://www.cdc.gov/diabetes/basics/type2.html}