Important race/ethnicity subgroups at high risk of CV disease are underrepresented in type 2 diabetes CV outcomes trials, limiting the strength of conclusions drawn. Until data are available, TMLE may be more efficient than conventional analysis, giving a better estimation of treatment effects to support clinical decision-making. TMLE makes minimal assumptions on data distribution and prioritizes fitting the most salient parts of the data to the statistical estimand, thus producing more precise and less biased estimates. Relative cumulative risk (RR) of major adverse CV events at 4 years with liraglutide vs. placebo for race/ethnicity subgroups in LEADER was estimated by TMLE + super learner. Comparison to the original Cox regression hazard ratio (HR) and unadjusted Kaplan-Meier RR is shown. Although RR and HR are different estimands, for rare events and proportional hazards they can be numerically close. While the original HR was not significant in any race/ethnicity subgroups, TMLE led to statistically significant treatment effects in all but the ‘Black’ subgroup (Figure) . Statistical power to detect the full population RR in the ‘Black’ subgroup was 0.13 (vs. 0.70 in the ‘White’ subgroup) . These data provide reassurance on the beneficial effects of liraglutide vs. placebo on CV outcomes in underpowered race/ethnicity subgroups.
D.Chen: None. T.J.Abrahamsen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. L.E.E.Dang: Research Support; Novo Nordisk. J.Lawson: Employee; Novo Nordisk A/S. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd.
Novo Nordisk A/S