Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes

Background: Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs. Methods: We implemented the post-stratifcation approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specifc estimates available from CVOTs to calculate expected efect size for the target population by weighting the average of the stratum-specifc treatment efects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confdence intervals. Results: Compared to the target population (n=139,708), the CVOT population (n=95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specifc efects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratumspecifc information. The post-stratifcation HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74–1.03) in the target population, compared to 0.86 (0.74–0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77–0.99) in the target population compared to 0.87 (0.78–0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The efect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population. Conclusions: Based on CVOT stratum-specifc efects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much diferent real-world population of patients with T2D.