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Emulating a Randomized Controlled Trial of Long-Acting Insulins and Cardiovascular Events Using Real-World Data for
Wanning Wang1,2, Pauline Reynier2, Michael Webster-Clark2,3
1Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
Pharmacoepidemiology and Drug Safety
|January 6, 2026
Summary
This study emulated the DEVOTE trial using real-world data to assess major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients on insulin degludec versus glargine. Findings were consistent with the DEVOTE trial in the overall and eligible populations.
Area of Science:
- Cardiology
- Endocrinology
- Real-world evidence research
Background:
- Randomized controlled trials (RCTs) offer high internal validity but limited generalizability.
- Real-world data (RWD) can enhance the generalizability of clinical trial findings.
- No prior studies have emulated RCTs using RWD to assess cardiovascular risk in type 2 diabetes mellitus (T2DM) patients on long-acting insulin analogues.
Purpose of the Study:
- To emulate the DEVOTE trial using RWD to evaluate the risk of major adverse cardiovascular events (MACE).
- To compare MACE risk between insulin degludec and insulin glargine in T2DM patients.
- To assess consistency of findings between RWD emulation and the original RCT across different patient subpopulations.
Main Methods:
- Emulation of the DEVOTE trial using the UK's Clinical Practice Research Datalink.
- Creation of DEVOTE-eligible and ineligible subpopulations.
- Application of Cox proportional hazards models with inverse probability of treatment weighting (IPTW) to estimate hazard ratios (HRs) and confidence intervals (CIs).
Main Results:
- Analysis included 10,430 patients in the overall population.
- The overall (HR: 1.36, 95% CI: 0.83, 1.86) and DEVOTE-eligible (HR: 1.07, 95% CI: 0.63, 1.58) populations showed results compatible with the DEVOTE trial (HR: 0.91, 95% CI: 0.78, 1.06).
- The DEVOTE-ineligible population exhibited wider confidence intervals and divergent point estimates (HR: 2.19, 95% CI: 0.30, 3.83) due to a low event count.
Conclusions:
- The MACE risk associated with insulin degludec versus insulin glargine in T2DM patients was consistent between the real-world overall population and the DEVOTE-eligible subpopulation.
- Discrepant point estimates were observed in the DEVOTE-ineligible subpopulation.
- RWD emulation can provide valuable insights into the generalizability of RCT findings for long-acting insulin analogues in T2DM.
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