Real-World Replication Program Emulates CANVAS, LEADER, SAVOR-TIMI Trials for Type 2 Diabetes Drugs

Randomized Controlled Trials (RCTs) are the gold standard for drug efficacy, but their findings may not always generalize to diverse real-world populations. Type 2 Diabetes Mellitus (T2DM) management relies on drugs like SGLT2 inhibitors and GLP-1 agonists. The HARRP program addresses this gap by systematically replicating key T2DM cardiovascular outcome trials (CVOTs) using real-world data, aiming to validate RCT findings and enhance understanding of drug performance in routine clinical practice. This initiative is crucial for bridging the evidence gap between controlled trial settings and heterogeneous patient populations.

The Harmonizing RCT-Duplicate Emulations (HARRP) program, sponsored by AstraZeneca, is a real-world replication study designed to emulate three pivotal Type 2 Diabetes Mellitus trials: CANVAS, LEADER, and SAVOR-TIMI. The program utilized real-world data from 239,990 patients, sourced via the Instant Health Data platform PANALGOS. It aimed to replicate the original trial findings for Canagliflozin (CANVAS), Liraglutide (LEADER), and Saxagliptin (SAVOR-TIMI), comparing them against DPP4 inhibitors or 2nd generation Sulfonylureas as reference drugs. The methodology involved creating duplicate cohorts from RWD to mirror the original RCT designs and assess their primary and secondary endpoints.

This clinical trial registration describes the design and completion of the HARRP program, but the specific findings from the real-world replication of the CANVAS, LEADER, and SAVOR-TIMI trials are not detailed in this record. The program's objective was to assess whether the cardiovascular and renal outcomes observed in the original randomized controlled trials for Canagliflozin, Liraglutide, and Saxagliptin could be reproduced using real-world data. Detailed statistical analyses, including hazard ratios, p-values, and confidence intervals for primary and secondary endpoints, are expected to be published separately. Therefore, no specific numerical findings or statistical outcomes can be reported from this registration entry, as it serves as a record of the study's design and completion rather than its results. The program is COMPLETED, indicating data collection and analysis are finished.