Biosimilar Liraglutide for T2D Noninferior to Reference Product, Study Finds

New results from a phase 3 clinical noninferiority trial reported biosimilar liraglutide (Melitide) was non-inferior in efficacy to the reference product (Victoza), with a comparable safety profile, suggesting its benefit for patients with type 2 diabetes (T2D).¹

The biosimilar showed a similar lowering of hemoglobin A1c (HbA1c) levels over 26 weeks of treatment, as well as comparable effects on body weight, lipid profile, blood pressure, and the incidence of adverse events.

“The results of this study indicate that [biosimilar liraglutide] is effective and safe for use in T2D patients,” wrote the investigative team, led by Dr. Mohammad Ebrahim Khamseh, Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences.

Approved by the US Food and Drug Administration (FDA) in January 2010, liraglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) used for glycemic control in adults with T2D. Based on trial data, the agent effectively controls blood glucose and reduces body weight in T2D.² Given the increasing incidence of diabetes, low-cost, effective medications are necessary to alleviate the subsequent burden on the healthcare system.

Pre-clinical studies have suggested no meaningful differences between a biosimilar liraglutide and the reference product. In the analysis, Khamseh and colleagues assessed the noninferiority, as well as other efficacy measures and safety, over a 26-week treatment period. The randomized, double-blind, active-controlled, parallel-group, noninferiority phase 3 clinical trial was conducted from July 2019 to December 2021 across 17 study centers in Iran.¹

Adults with inadequately controlled T2D and HbA1c levels 7–10.5% on 2 or more oral glucose-lowering medications with stable doses for 3 months or longer were randomized 1:1 to receive daily 1.8mg biosimilar liraglutide or liraglutide for 26 weeks. The study’s primary outcome was an assessment of noninferiority between the 2 agents regarding the change in HbA1c at week 26, with a prespecified margin of 0.4%.

Secondary outcomes included the percentage of patients achieving HbA1c targets (HbA1c <7%; HbA1c ≤6.5%), as well as changes in body weight, fasting plasma, blood pressure, pulse rate, lipid profile, and estimated glomerular filtration rate (eGFR) from baseline to week 26. The incidence of adverse events and immunogenicity were additionally assessed by investigators.

A total of 521 patients were screened and 300 met the inclusion criteria, with 150 patients assigned to each study arm. A total of 235 patients were included in the per-protocol analysis, including 112 receiving biosimilar liraglutide and 123 receiving liraglutide. Upon analysis, in both study arms, HbA1c levels decreased over the first 12 weeks and remained stable until week 26 of treatment.

The mean changes in HbA1c from baseline to week 26 were –1.76% in the biosimilar liraglutide group and –1.59% in the liraglutide group (difference, –0.18; 95% CI, –0.50 to 0.15; P = .288). Investigators noted the upper limit of the one-sided 95% CI for the mean difference between the 2 study arms was lower than the predefined noninferiority margin (0.4%), suggesting the noninferiority of the biosimilar to the reference product in lowering HbA1c. These findings were consistent in the intention-to-treat analysis, according to investigators.

The analysis of secondary outcomes included 112 patients in the biosimilar liraglutide and 125 patients in the liraglutide groups. Investigators identified no statistically significant differences between the 2 study arms regarding the proportion of patients achieving HbA1c <7% (P = .210) other efficacy parameters (P > .05) or reported adverse events (P = .916).

Overall, 126 (83.44%) patients in the biosimilar liraglutide group and 125 (83.89%) patients in the liraglutide group experienced ≥1 adverse event, with most considered mild or moderate. The observed safety profiles matched those reported in other studies investigating liraglutide. Serum samples from 134 patients in each study arm revealed no patient developed anti-liraglutide antibodies.

“A longer treatment duration and a relatively larger sample size might have enabled us to detect differences between the two medications in terms of rare adverse events,” investigators wrote.

References

1. Esteghamati, A., Zamanzadeh, M., Malek, M. et al. Efficacy and Safety of a Biosimilar Liraglutide (Melitide®) Versus the Reference Liraglutide (Victoza®) in People with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Noninferiority Clinical Trial. Diabetes Ther (2023). https://doi.org/10.1007/s13300-023-01462-w
2. Liraglutide - Drug approval package. Victoza (Liraglutide [rDNA]) Injection. April 20, 2010. Accessed September 22, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022341s000TOC.cfm#:~:text=Approval%20Date%3A%201%2F25%2F2010.