[Sulphonylurea derivatives or insulin with metformin?]

If pharmacological treatment of glycaemia with metformin in patients with type 2 diabetes fails, a second agent is advised, however, the optimal choice is unclear. Most guidelines suggest the addition of sulphonylurea (SU) derivatives as the first option, but sometimes insulin is preferred as there have been doubts concerning the cardiovascular safety of SUs. From a large Veterans Administration (VA) registry study, Roumie et al. extracted patients on metformin who received additional treatment with either SU (majority) or insulin, and compared the number of cardiovascular endpoints over the subsequent 7-year period. The number of endpoints was higher in the metformin+insulin group than in the metformin+SU group, with a relative risk of 1.3. The authors conclude that when compared with the addition of SU the addition of insulin to metformin is associated with an elevated risk of a cardiovascular endpoint. While the authors have performed multiple adjustments for potential differences in the two treatment groups, this is in fact a retrospective cohort study and hence selection bias cannot be excluded. Nevertheless, the results suggest that the current guidelines/practice of adding SU to metformin is at least as safe as adding insulin and should not be changed.