Efficacy and safety of biosimilar insulins compared to their reference products: A systematic review.

IMPORTANCE: For nearly a century, no generic form of insulin has been available in the United States. However, the first biosimilar insulin, Basaglar, was approved by the U.S. Food and Drug Administration in 2015, and subsequently Admelog and Lusduna in 2017.

OBJECTIVE: To summarize the scientific evidence comparing the safety, efficacy, pharmacokinetics, and pharmacodynamics of biosimilar and reference insulin products.

DATA SOURCES: We conducted a systematic review using PubMed, Cochrane, Embase, Latin America and Caribbean Health Sciences, South Asian Database of Controlled Clinical Trials, and IndiaMED from their inception through January 14, 2018.

STUDY SELECTION: We included randomized controlled trials (RCTs) comparing safety, clinical efficacy, pharmacokinetics and pharmacodynamics of any biosimilar insulin with a reference product in adults regardless of sample size and location.

DATA EXTRACTION AND SYNTHESIS: Two researchers independently reviewed all titles, abstracts and text; extracted data; and performed quality assessments.

MAIN OUTCOMES AND MEASURES: Efficacy, safety, pharmacokinetics, and pharmacodynamics of biosimilar and reference insulin products.

RESULTS: Of 6945 articles screened, 11 studies were included in the data synthesis. LY2963016, Basalog, Basalin, and MK-1293 were compared to Lantus while SAR342434 was compared to Humalog. Three trials enrolled healthy volunteers, five enrolled type 1 diabetics, and two enrolled type 2 diabetics. One study enrolled both healthy and type 1 diabetics. Of the eleven studies, six examined pharmacokinetic and/or pharmacodynamic parameters and five examined clinical efficacy and immunogenicity. All studies included adverse events. All PK and/or PD studies showed that comparable parameters of biosimilar and reference products were within the pre-specified equivalence margins. Clinical studies suggested similar clinical efficacy and immunogenicity. Adverse events were similar between the groups across all studies.

CONCLUSIONS AND RELEVANCE: Few published studies have compared biosimilar and reference insulins, though those that did suggest that the biosimilars have comparable safety and clinical efficacy as its reference product.