Statistical methods
fasting blood glucose, diabetes
REGRESSION, EVENTS, SECONDARY, DIABETES
Primary analyses were by intention-to-treat and included participants who were randomised and had at least one valid measurement of primary or secondary outcomes. A linear mixed model was employed for the primary endpoint analysis. The linear mixed model included treatment (metformin vs placebo), visit (midpoint and study end [i.e. approximately 6 and 12 months, respectively]), and the interaction between treatment and visit as fixed effects, controlling for baseline blood glucose values at 2 h post 75 g glucose load, and including a participant level random intercept. Restricted maximum likelihood estimation was used to fit the linear mixed model, assuming an unstructured covariance matrix. The Satterthwaite approximation for the degrees of freedom was used. This model was used to determine the difference in means of glucose levels 2 h post 75 g glucose load (and two-sided 95% CI) between the two treatment arms at midpoint and endpoint. A two-sided Continuous secondary outcomes were analysed in a similar way as the primary endpoint. For the analysis of binary secondary outcomes, a generalised linear mixed model was employed with treatment, visit, and interaction between treatment and visit as fixed effects, controlling for baseline values of each respective outcome, and including a participant level random intercept. For blood lipids, which were only measured at baseline and 12 month follow-up, estimates were derived using linear regression models controlling for baseline values. The odds ratio between the two treatment arms at each visit, together with 95% CI, was derived from the generalised mixed model. The generalised linear model was used to analyse secondary outcomes with a single follow-up measurement, controlling for baseline values. The occurrence of diabetes was summarised using the number of events and incidence rate by treatment group and analysed using a generalised linear model with Poisson distribution and log link function and with treatment as a fixed effect, to generate incidence rate ratios (IRRs) and 95% CIs. Thresholds for diabetes were defined using the respective thresholds for fasting blood glucose (≥7.0 mmol/l), 2 h postprandial blood glucose level (≥11.1 mmol/l) and HbAAnalyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC, USA). A 