Therapeutic equivalence and switching between biosimilar and reference insulins: A systematic review and...

To comprehensively evaluate the therapeutic equivalence and switching between biosimilar insulins and reference insulins in efficacy, safety and immunogenicity in diabetes.

MEDLINE (via PubMed), Embase and Cochrane Library were searched (inception to March 2025) for randomised controlled trials (RCTs) employing two designs: (1) therapeutic equivalence trials directly compared biosimilar insulins vs. reference insulins; (2) switching trials where participants initially received reference insulin during a run-in period and were then randomised to either switch to biosimilar insulins or continue reference insulins. Outcomes included change in glycated hemoglobin (HbA1c) (%), achievement of HbA1c < 7%, change in fasting blood glucose (FBG), adverse events and immunogenicity. Heterogeneity was examined with I² statistics. Data were pooled using mean differences (MDs) for continuous variables and odds ratios (ORs) for binary outcomes with 95% confidence intervals (CIs).

A total of 25 RCTs involving 10 617 patients were included: equivalence analysis of 16 RCTs (n = 6548 patients) and switching analysis of nine RCTs (n = 4069 patients). No significant differences were found for change in HbA1c (equivalence: MD 0.01%, 95% CI -0.04, 0.06; switching: MD -0.01%, 95% CI -0.06, 0.05), the proportion achieving HbA1c <7.0% (equivalence: OR 0.99, 95% CI 0.88, 1.12; switching: OR 1.05, 95% CI 0.86, 1.27), or change in FBG (equivalence: MD 0.08 mmol/L, 95% CI -0.06, 0.22; switching: MD 0.11 mmol/L, 95% CI -0.18, 0.40).

No statistically significant differences were found in the efficacy, primary safety and immunogenicity between biosimilar insulins and reference insulins. These findings support biosimilar insulins' adoption to enhance treatment access and cost-effectiveness.