@article {Patornodc190069, author = {Patorno, Elisabetta and Schneeweiss, Sebastian and Gopalakrishnan, Chandrasekar and Martin, David and Franklin, Jessica M.}, title = {Using Real-World Data to Predict Findings of an Ongoing Phase IV Cardiovascular Outcome Trial: Cardiovascular Safety of Linagliptin Versus Glimepiride}, elocation-id = {dc190069}, year = {2019}, doi = {10.2337/dc19-0069}, publisher = {American Diabetes Association}, abstract = {OBJECTIVE Using real-world data (RWD) from three U.S. claims data sets, we aim to predict the findings of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA) trial comparing linagliptin versus glimepiride in patients with type 2 diabetes (T2D) at increased cardiovascular risk by using a novel framework that requires passing prespecified validity checks before analyzing the primary outcome.RESEARCH DESIGN AND METHODS Within Medicare and two commercial claims data sets (May 2011{\textendash}September 2015), we identified a 1:1 propensity score{\textendash}matched (PSM) cohort of T2D patients 40{\textendash}85 years old at increased cardiovascular risk who initiated linagliptin or glimepiride by adapting eligibility criteria from CAROLINA. PSM was used to balance \>120 confounders. Validity checks included the evaluation of expected power, covariate balance, and two control outcomes for which we expected a positive association and a null finding. We registered the protocol (NCT03648424) before evaluating the composite cardiovascular outcome based on CAROLINA{\textquoteright}s primary end point. Hazard ratios (HR) and 95\% CIs were estimated in each data source and pooled with a fixed-effects meta-analysis.RESULTS We identified 24,131 PSM pairs of linagliptin and glimepiride initiators with sufficient power for noninferiority (\>98\%). Exposure groups achieved excellent covariate balance, including key laboratory results, and expected associations between glimepiride and hypoglycemia (HR 2.38 [95\% CI 1.79{\textendash}3.13]) and between linagliptin and end-stage renal disease (HR 1.08 [0.66{\textendash}1.79]) were replicated. Linagliptin was associated with a 9\% decreased risk in the composite cardiovascular outcome with a CI including the null (HR 0.91 [0.79{\textendash}1.05]), in line with noninferiority.CONCLUSIONS In a nonrandomized RWD study, we found that linagliptin has noninferior risk of a composite cardiovascular outcome compared with glimepiride.}, issn = {0149-5992}, URL = {https://care.diabetesjournals.org/content/early/2019/07/05/dc19-0069}, eprint = {https://care.diabetesjournals.org/content/early/2019/07/05/dc19-0069.full.pdf}, journal = {Diabetes Care} }