Quantifying Heterogeneity within and between Treatment Guidelines for Type 2 Diabetes: Potential Implications for EU-Wide Health Technology Assessment

OBJECTIVES: By 2030, the European Union (EU) will require manufacturers to submit a Joint Clinical Assessment (JCA) dossier for new therapies, aiming to harmonize health technology assessment across the EU. This will require all 27 member states to define relevant PICO (population, intervention, comparator, outcome) requirements. In type 2 diabetes (T2D), step-wise intensification is often required to maintain glycemic control, with recommendations at each therapy line creating branched treatment pathways. This review quantifies the heterogeneity in managing T2D in EU guidelines and the implications for the JCA process.

METHODS: A systematic literature review was performed in PubMed and guideline-specific databases to identify T2D treatment guidelines. Searches were performed in May 2021 and limited to publications from 2016 onwards, ensuring reflection of modern treatment practices. Treatment pathways were extracted based on medications initiated and discontinued at each step (e.g., metformin followed by sulfonylurea followed by basal insulin), and the characteristics of the specified population.

RESULTS: Review of 13 EU-specific T2D guidelines yielded 427 unique treatment pathways, covering up to seven lines of therapy. Guidelines defined seven subpopulations, most commonly people with (or with high risk of) cardiovascular disease, renal disease, or hypoglycemia. Recommendations were consistent for first-line therapy, with metformin specified in over 70% of pathways. Second- and third-line therapy varied more, with no single treatment option recommended in more than 35% of pathways. The diversity of recommendations led to several medications being indicated at almost every position in the pathway.

CONCLUSIONS: Consolidating PICO requests for the JCA of new T2D interventions could be challenging due to the heterogeneity in treatment guidelines, potentially leading to complex evidence generation needs and delays in reimbursement of efficacious medications. Collaboration between regulators, healthcare professional associations and patient organizations to mitigate complexity could represent a strategy to successfully implement the JCA process for T2D interventions.