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Aims/hypothesis At present, no disease-modifying therapies are available for individuals who have been newly diagnosed with type 1 diabetes, despite promising results from decades of clinical trials initiated at stage 3 disease onset. Historically, clinical trials have used changes in the C-peptide AUC (AUCCp) during a mixed meal tolerance test (MMTT) as the primary endpoint; however, this measure does not always correlate with clinical outcomes. Methods We analysed 4930 MMTT data points from 799 participants in nine Phase II stage 3 type 1 diabetes trials to determine whether a model-derived physiological measure of in vivo beta cell glucose sensitivity (βGS) could augment clinical trial strategies in type 1 diabetes. Results Older age and higher BMI were associated with maintenance of βGS (defined as loss <10% of the baseline value) and maintenance of HbA1c <53 mmol/mol (7.0%). Baseline βGS, age, HbA1c and insulin dose together predicted the magnitude of the effect on HbA1c following intervention. When positive and negative trials were compared, normalised βGS served as an earlier indicator of trial efficacy compared with AUCCp. Conclusions/interpretation Our results identified thresholds of change in βGS associated with a clinically significant impact on glycaemic management after intervention and suggest that baseline βGS in association with clinical and demographic parameters may be applied to identify individuals who are more likely to respond to an intervention. Graphical Abstract