Extended Data Fig. 5: Estimated marginal means for linear mixed models of cognitive and WMTI outcomes.

Data are presented as estimated marginal means from seperate general linear mixed models (two sided) with two sets of outcomes (Outcome 1 and 2 corresponding to the end of the first and second 12-week treatment cycles, respectively). We examined the fixed effects of cycle (the first versus second 12-week treatment cycle), treatment (metformin versus placebo), and sequence (metformin first, placebo second [AB] versus placebo first, metformin second [BA]). Bar graphs show estimated means+/- SEMs from the following model: Outcome measure = cycle + treatment + sequence + covariate (Baseline measure) + (1| participant ID)+ε, where cycle, treatment, and sequence are independent fixed effects and where the measures are: a) total correct on the LSWM (n = 23); b) CANTAB mean latency (n = 22); c) total number of words recall for immediate recall (n = 23); and d) AWF. Standard error bars are shown for each estimated mean. All models were corrected for multiple comparisons (False Discovery Rate (FDR) q < .10): * p < 0.05, ** q < 0.10 from the linear mixed models (Panel a-c, qs = 0.09; Panel d, q = 0.08).