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Abstract Background Robust identification of surrogate endpoints can help accelerate the development of pharmacotherapies for diseases traditionally evaluated using true endpoints associated with prolonged follow-up. The meta-analysis-based surrogate endpoint evaluation (SEE) integrates data from multiple, usually smaller, trials to statistically confirm a surrogate endpoint as a robust proxy for the true endpoint. To test the applicability of SEE when only a single, larger trial is available, we analysed the cardiovascular (CV) survival endpoint from the large multinational trial LEADER (9340 subjects) that confirmed the CV safety of a diabetes drug (liraglutide). We evaluated if using country as a trial unit adequately facilitated the meta-analysis and calculation of R2 by country group. Methods Data were grouped by country, ensuring at least 30 CV deaths (497 in total) in each of the nine resulting by-country groups. In a two-step SEE on the grouped dataset, we first fitted the group-specific Cox proportional hazard models; next, on the trial-level, we regressed the estimated hazard ratio (HR; liraglutide vs placebo) of the true endpoints (CV death: 497 events, or all-cause death: 828 events) on the HR of the surrogate endpoint (major CV adverse event [MACE]: 1302 events) and derived the group-specific R2 and its 95% confidence interval (CI). Results Group-level surrogacy of MACE was supported for CV death but not for all-cause death, with $${\text{R}}_{{{\text{group}}}}^{2}$$ R group 2 values of 0.85 [0.63;1.00]95% CI and 0.23 [0.00;0.67]95% CI, respectively. Sensitivity analyses using different grouping approaches (e.g. grouping by region) corroborated the robustness of the conclusions as well as the appropriateness of the data-grouping approaches. Conclusions We derived a specific grouping approach to successfully apply SEE on data from a single trial. This may allow for the statistically robust identification and validation of surrogate endpoints based on the abundance of large monolithic outcome trials conducted as part of drug development programmes in, for example, diabetes.