Adjusted hazard ratios for all-cause mortality for insulin plus metformin compared with insulin monotherapy.

<p>Notes: Final model specification: estimated cumulative insulin dose, therapy (±metformin), HbA1c, BMI, diabetes duration, index year, insulin regimen, smoking status, serum creatinine, prior cancer, prior large vessel disease, prior lipid-lowering therapy, prior anti-hypertensive therapy, prior anti-platelet therapy, prior GP contacts, Charlson comorbidity index, gender, and age at index. Insulin dose (units/kg/day) was added as a cumulative dose as an annually updated, time-dependent covariate. Baseline values were used for the remaining covariates as defined in the Statistical Methods section. Prior anti-hypertensive therapy and history of cancer violated the proportional hazards assumption of the Cox model and so were added as Heaviside functions (<1,095 and ≥1,095 days). The covariate used to categorize each subgroup was removed from the model for the respective analysis.