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 veteran population

Abstract

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.

Cardiovascular safety in type 2 diabetes with sulfonylureas as second-line drugs: a nation-wide population based comparative safety study

“…Our subgroup analyses showed little difference between second-generation SU. The difference in CV outcome observed in this study compared with older observational studies could be explained by gliclazide being the SU of choice within Scotland (87.2% of second-line SU users), while other studies included high use of SU with high cardiac K ATP and mitochondrial KATP affinity such as glibenclamide (35,36). Furthermore, some existing observational diabetesjournals.org/care studies reporting higher CV risk of SU included a high proportion of people who switch from metformin to SU; including SU users who switched from metformin but remained on first-line monotherapy may contaminate the treatment effect estimates.…”

Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study

“…Our subgroup analyses showed little difference between second-generation SU. The difference in CV outcome observed in this study compared with older observational studies could be explained by gliclazide being the SU of choice within Scotland (87.2% of second-line SU users), while other studies included high use of SU with high cardiac K ATP and mitochondrial KATP affinity such as glibenclamide ( 35 , 36 ). Furthermore, some existing observational studies reporting higher CV risk of SU included a high proportion of people who switch from metformin to SU; including SU users who switched from metformin but remained on first-line monotherapy may contaminate the treatment effect estimates.…”