These factors could provide a scientific basis for consistency evaluations of the quality and efficacy of insulin biosimilars, study authors wrote.
Factors that may affect the bioequivalence of test and reference insulin preparations were identified in a new study published in Frontiers in Pharmacology. Going forward, these factors can provide a scientific basis for consistency evaluations of the quality and efficacy of insulin biosimilars, authors wrote.
Findings from a structural equation model led researchers to conclude “adverse events and bioactive substance content should be optimized for consistency evaluation of the quality and efficacy of insulin biosimilars.”
The structural equation model allows for multivariable analysis, and compared with general regression analysis, it can better control measurement error. In addition, the authors wrote that “bioequivalence trials of insulin biosimilars should strictly obey inclusion and exclusion criteria to ensure the consistency of subjects and avoid confounding factors affecting the equivalence evaluation.”
For patients with diabetes, research has shown insulin biosimilars can better simulate the human physiological state of insulin secretion patterns and achieve a more flexible dosing time, along with other benefits.
“Bioequivalence evaluation is the established way for the review of generic drugs and occupies an important position in generic drug applications,” the authors explained, while biosimilars and their references should also be bioequivalent in safety and efficacy.
Several factors affect insulin preparations’ evaluations of bioequivalence, including the drugs’ properties and patients’ physiological status.
To better understand the factors affecting bioequivalence of 2 preparations, the researchers analyzed 177 healthy male patients between aged 18 to 45 years. Participants were divided into the equivalent group (n = 55) and nonequivalent group (n = 122) based on bioequivalence results according to European Medicines Agency guidelines.
Researchers used a 24-hour glucose clamp test to measure the glucose infusion rate and blood glucose. Liquid chromatography–mass spectrometry (LC-MS/MS) was also used to determine plasma insulin concentration.
A univariate analysis revealed statistical differences in “albumin, creatinine, Tmax, bioactive substance content, and adverse events between the 2 groups,” data showed.
Furthermore, the structural equation model showed both adverse events (β = 0.342; P < .001) and bioactive substance content (β = −0.189; P = .007) had significant impacts on the 2 preparations’ bioequivalence, while “the bioactive substance content significantly affected adverse events (β = 0.200; P = .007).”
Adverse events included abnormalities in the liver and kidney function indicators, which could affect the drugs’ metabolic process. “Pharmaceutical preparation factors can also affect the occurrence of adverse events because of their active ingredients, impurity profiles, and excipients,” the authors added.
Because C-peptide levels in all insulin formulas were inhibited, they noted the bioequivalence evaluations carried out could exclude any interference from endogenous insulin.
The study marked the first time, to the authors’ knowledge, that researchers analyzed factors influencing the bioequivalence of insulin biosimilars based on structural equation models.
Overall, the authors offer the following advice based on the findings:
A small sample size and lack of female participants mark limitations to the study. The indicators collected may also not comprehensively evaluate the influencing factors of bioequivalence, the researchers concluded.
Reference
Shao H, Tao Y, Tang C. Factors influencing bioequivalence evaluation of insulin biosimilars based on a structural equation model. Front Pharmacol. Published online April 3, 2023. doi:10.3389/fphar.2023.1143928
Frameworks for Advancing Health Equity: Urban Health Outreach
May 9th 2024In the series debut episode of "Frameworks for Advancing Health Equity," Mary Sligh, CRNP, and Chelsea Chappars, of Allegheny Health Network, explain how the Urban Health Outreach program aims to improve health equity for individuals experiencing homelessness.
Listen
Study Highlights Significant Increases in Utilization, Spending on DMD Drugs in Medicaid
May 17th 2024The findings add to recent research on the growing utilization, expenditure, and prices of Duchenne muscular dystrophy (DMD) therapies in the current landscape, an area health care policy could potentially address.
Read More
Perioperative Nivolumab Boosts NSCLC Survival: CheckMate 77T Trial
May 16th 2024This interim analysis of the CheckMate 77T trial, outcomes were compared between adult patients receiving neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo for resectable non–small cell lung cancer (NSCLC).
Read More