Additional analyses to original Statistical Analysis Plan
ADVERSE EVENTS, MINOR, SIDE EFFECT
There were no major changes to the analysis proposed compared with the original statistical analysis plan, but some minor additional analysis was carried out to explore differences in side effects (any v none) between drugs and strata, as a way of capturing the overall burden of side effects. A strata specific analysis for each side effect would entail multiple testing without prior hypotheses and increased likelihood of type 1 errors, so this was deemed inappropriate.We also report numbers of adverse events for each drug, split by severity and relatedness and whether they were associated with withdrawal or non-tolerability.A further sensitivity analysis was conducted to explore the impact of residual autocorrelation arising from time trends or treatment carryover on the main effect sizes (drug/strata interactions). The mixed effects models for the primary analysis were extended by defining an exponential autocorrelation structure for the residual errors. This allowed for the pairwise correlation between HbA1c measurements to decrease systematically as the time gap increased and could account for irregularly spaced intervals.Finally, we added in scatterplots to show the association on a continuous scale between each of BMI and eGFR against the difference in HbA1c for the two drugs of interest for each hypothesis. We present Pearson correlation coefficients to show the strength of associations alongside these.