Cardiometabolic & kidneySecondary analysis
Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes
- Secondary analysis of the EXSCEL randomised trial
- placebo-controlled
Authors' conclusion
EXSCEL-observed HRs for MACE and ACM remained robust after right censoring or application of literature-derived risk reductions, but the exenatide versus placebo MACE effect size and statistical significance were increased by IPTW.
Study context
- Population
- Patients with T2DM (73.1% with previous CVD)
- Participants
- 14,752 patients
- Comparison
- Exenatide vs Placebo
- Primary endpoint
- MACE (CV death, nonfatal MI or nonfatal stroke) and all-cause mortality under drop-in visit right censoring, IPTW and applied drug class risk reductions
- Follow-up
- Median 3.2 years
Primary result
As reported in the abstract
MACE and ACM HRs (exenatide vs placebo) after adjustment for open-label drop-in · median 3.2 years
- Right censoring: Major adverse cardiovascular events (MACE) effect size not altered meaningfully; All-cause mortality (ACM) HR and P values essentially unchanged
- Inverse probability for treatment weighting (IPTW): MACE HR decreased from 0.91 (P=0.061) to 0.85 (P=0.008)
- IPTW: ACM HR decreased from 0.86 (P=0.016) to 0.81 (P=0.012)
- Literature-derived risk reductions: no meaningful changes in MACE or ACM HRs or P values
Further findings
Open-label drop-in of glucose-lowering medications · median 3.2 years
Metformin
Sulfonylurea
DPP-4 inhibitors
SGLT-2i
GLP-1 RA
Insulin
- Open-label drop-in of glucose-lowering medications — Overall open-label drop-in
- 33.4%
Original publication
Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes. Circulation. Published 26 February 2020. doi:10.1161/circulationaha.119.043353
Summarised from the published abstract; every number is checked against it