Biosimilar Insulin Pharmacodynamics in Diabetes Management

Biosimilar insulins are developed to match the molecular structure and clinical performance of approved insulin analogues, offering more affordable treatment options without compromising efficacy or safety. Understanding pharmacodynamics—the timing, intensity and duration of glucose-lowering action—is critical for optimising dosing regimens and minimising hypoglycaemia. Euglycaemic clamp studies remain the gold standard for quantifying insulin effect by measuring glucose infusion rates under controlled glycaemia. Demonstrating pharmacokinetic and pharmacodynamic equivalence within regulatory margins ensures interchangeability and can enhance global access to basal and rapid-acting insulin therapies. Recent advances focus on refining analytical methods, extending evaluations to diverse populations and exploring long-acting formulations to improve patient outcomes.

Research from Nature Portfolio

Two euglycaemic clamp crossover trials in healthy volunteers have reinforced the biosimilarity of rapid-acting insulin aspart formulations. One study compared a proposed insulin aspart biosimilar to the Japan-approved reference, finding identical peak concentrations and total exposure (INS-Cmax, INS-AUClast) alongside matching glucose infusion rate metrics (GIR‐AUC, GIRmax) within 80–125% equivalence bounds. A parallel investigation in Chinese male subjects evaluated a different aspart biosimilar against a market leader, confirming equivalent absorption profiles, onset of action and glucodynamic potency over a 10-hour clamp. Both trials reported no unexpected adverse events, supporting clinical interchangeability in prandial insulin management.

Biosimilar Insulin Pharmacodynamics in Diabetes Management publication trend

The graph below shows the total number of articles in biosimilar insulin pharmacodynamics in diabetes management across all publications each year (not limited to Nature Index journals).

Technical terms

Biosimilar insulin: A highly similar version of an authorised insulin analogue, matching the reference in structure, function and clinical performance.

Pharmacokinetics (PK): The study of how a drug is absorbed, distributed, metabolised and eliminated by the body.

Pharmacodynamics (PD): The analysis of a drug’s biological effects, including onset, intensity and duration of action.

Euglycaemic clamp: An experimental procedure that maintains constant blood glucose by variable glucose infusion to measure insulin-induced glucose uptake.

Area under the curve (AUC): The integral of a concentration-time or effect-time graph, representing total drug exposure or response.

Immunogenicity: The potential of a therapeutic protein to elicit immune responses, such as anti-insulin antibodies.

References

1. Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study. Frontiers in Pharmacology (2021).
2. Pharmacokinetic and pharmacodynamic similarity between SAR341402 insulin aspart and Japan-approved NovoRapid in healthy Japanese subjects. Scientific Reports (2021).
3. Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males. Scientific Reports (2021).
4. Pharmacokinetic and pharmacodynamic similarity evaluation between an insulin glargine biosimilar product and Lantus® in healthy subjects: Pharmacokinetic parameters of both parent insulin glargine and M1 were used as endpoints. Frontiers in Pharmacology (2022).
5. A comparative evaluation of bioequivalence of Gan & Lee glargine U300 and Toujeo® in Chinese healthy male participants. Frontiers in Endocrinology (2024).
6. Efficacy and immunogenicity of insulin biosimilar compared to their reference products: a systematic review and meta-analysis. BMC Endocrine Disorders (2022).