Long-term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second-line Type 2 diabetes mellitus treatment in a US Veterans Affairs population.

Aim To examine the risks of all-cause mortality and cardiovascular events associated with adding vs switching to second-line therapies in a comparative safety study of people with Type 2 diabetes mellitus. Methods We conducted a retrospective cohort study using an as-treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose-lowering treatments between 1998 and 2012. This study included 145 250 people with long follow-up. Confounding was addressed through several strategies, involving weighted propensity score models with rich confounder adjustment and strict inclusion criteria, coupled with an incident-user design. Results Second-line use of sulfonylureas was related to higher mortality (hazard ratio 1.39, 95% CI 1.14, 1.70) and cardiovascular risks (hazard ratio 1.19, 95% CI 1.09, 1.30) compared with thiazolidinedione therapy. Differential hazards were associated with discontinuing or not discontinuing metformin; switching to sulfonylurea therapy was associated with a higher risk of all-cause mortality and cardiovascular events compared with all other therapies. Furthermore, add-on sulfonylurea therapy was associated with an elevated risk for both outcomes when compared with thiazolidinedione add-on therapy. Conclusions The results of the present study may inform decisions on whether to augment or discontinue metformin; when considering the long-term risks, switching to a sulfonylurea appears unfavourable compared with other therapies. Instead, adding a thiazolidinedione to existing metformin therapy appears to be superior to adding or switching to a sulfonylurea.