Real world evidence of insulin and biosimilar insulin therapy-Opportunities to improve adherence, outcomes and cost-effectiveness.

Insulin has been discovered for more than a century; however, its benefits to people with diabetes are yet to be fully realized due to barriers related to access, quality of care and costs. Insulin therapy remains the cornerstone of diabetes management. The multicausality of diabetes and its subtypes calls for comprehensive phenotyping and use of biomarkers to ensure timely use of insulin to achieve early glycaemic control for long-term benefits. Biosimilar insulins are biologic products that closely resemble originator insulins without significant differences in safety or efficacy. The lower investment costs needed for research and development make biosimilar insulin more affordable to improve access. While the efficacy of insulin products is proven in controlled settings, real world evidence (RWE) from real world data (RWD) plays a crucial role in assessing the safety, efficacy, cost-effectiveness, adherence to and impacts of different insulin products, including biosimilars, on clinical outcomes. In this narrative review, we summarized the trends of insulin use and patterns of biosimilar insulin utilization in real world practice across different regions. We reviewed RWE on clinical safety, efficacy and cost-effectiveness of biosimilar insulin, as well as therapeutic inertia and non-adherence with insulin therapy. We also highlighted barriers to insulin adherence and enablers for persistence, along with potential solutions to promote the use of insulin and technologies for optimizing glycaemic control in different subtypes of diabetes. During our extensive literature review, we identified data gaps in the usage of biosimilar insulin in real world practice. We advocate for implementing a diabetes register designed fit-for-purpose, managed by a trained doctor-nurse team with system support, to generate RWE. By setting up registers with structured data collection, we can generate high quality data for integrative analysis with electronic health records (EHR) and health claims to evaluate the impacts of insulin products and other diabetes programmes on clinical outcomes, quality of life and healthcare costs to inform practice and policies. PLAIN LANGUAGE SUMMARY: Diabetes affects approximately 10.5% of the global population and insulin is a vital treatment for diabetes management. Insulin was discovered more than a century ago, although its benefits to people with diabetes are yet to be fully realized due to barriers related to access, quality of care, and costs. Real-world evidence from real-world data plays a crucial role in assessing the safety, efficacy, cost-effectiveness, adherence to, and impacts of different insulin products, including biosimilars, on clinical outcomes. In this publication, the authors provided a detailed review of the patterns of use and cost-effectiveness of biosimilar insulin, and identified major data gaps. The authors explained the methodology, utility, and limitations of generating real-world evidence based on real-world data from sources such as registers, electronic health records and health claims for assessing treatment effectiveness and safety. The authors proposed the implementation of a purpose-built diabetes register with structured data collection, managed by a trained doctor-nurse team with system support. These high-quality data can be integrated with electronic health records and health claims for evaluation of interventions, including insulin on outcomes, quality of life, and costs to inform practice and policy. Based on these premises and available data, the authors summarized trends in insulin use including biosimilar insulin, and reviewed real-world evidence on the safety, efficacy, and cost-effectiveness of these products. They also identified barriers like therapeutic inertia and non-adherence, discussed enablers for persistence, and proposed solutions to evaluate the impacts of insulin products and other diabetes programs on clinical outcomes, quality of life, and healthcare costs to inform practice and policies.