OBJECTIVES: Given the progressive nature of T2DM, treatment is often characterised by gradual intensification, ultimately requiring multiple daily insulin injections. CANA and DAPA are agents with activity on SGLT2 that may delay the need for insulin. Network meta-analyses (NMAs) have found that CANA 300 mg lowers HbA1c more than DAPA in dual and triple therapy. Mechanistic differences support these results. Specifically, CANA 300 mg has been shown to reduce the renal threshold for glucose excretion more than DAPA 10 mg, resulting in 25% greater 24-hour urinary glucose excretion. In addition, unlike DAPA, CANA 300 mg may transiently block intestinal SGLT1, delaying glucose absorption and reducing postprandial glucose. This study evaluates differences in time to insulin initiation using CANA versus DAPA as dual and triple therapy in the Irish healthcare setting. METHODS: A validated model (ECHO-T2DM) was used to simulate 40-year costs and outcomes associated with canagliflozin (100 mg, titrated to 300 mg in patients requiring tighter glycaemic control) compared to DAPA (10 mg). Insulin rescue therapy was initiated when HbA1c exceeded 7.5%. The CANA RCTs and the NMAs were sourced for initial patient characteristics and treatment effects, respectively. RESULTS: In dual therapy, insulin rescue was delayed by 1.7 years on average for CANA titrated to goal (4.8 years) versus DAPA (3.1 years). In triple therapy, insulin therapy was delayed by 1.8 years on average for CANA titrated to goal (5.1 years) versus DAPA (3.3 years). Much of the difference was driven by the ability to titrate to CANA 300 mg for additional glycaemic control. CONCLUSIONS: These simulations suggest that treatment with CANA versus DAPA could delay insulin initiation by 55% in both dual and triple therapy. This difference may translate into delays in undesirable health outcomes and the financial burden associated with injectables in actual practice.
Bacon, T., Willis, M., Johansen, P., & Neslusan, C. (2015). Time Until Insulin Initiation for Canagliflozin (Cana) versus Dapagliflozin (Dapa) In dual and triple Therapy for type 2 diabetes mellitus (T2dm) In Ireland. Value in Health, 18(3), A55. https://doi.org/10.1016/j.jval.2015.03.324