Cardiovascular Safety in Type 2 Diabetes with Sulfonylureas as Second-Line Drugs

Type 2 diabetes is associated with increased risk of microvascular and macrovascular disease, with the risk of cardiovascular (CV) mortality more than double in people with type 2 diabetes (T2D) compared with those without. Sulfonylureas (SU) are potent glucose lowering agents that have been widely used in the management of type 2 diabetes for over 60 years.

The objective of this study was to assess the real-world CV safety for SUs, in comparison with dipeptidylpeptidase-4 inhibitors (DPP4i) and thiazolidinediones (TZD). To do it, the study was performed including people with T2D diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48mmol/mol (<6.5%) despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) from 1 January 2010.

The primary outcome was a composite one, including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death and as secondary outcomes, each individual end point and all-cause death.

At the end of the study, comparing SU to non-SU treatments (DPP4i/TZD), the findings provided real-world evidence to support the conclusion that SUs prescribed as second- line are safe regarding CV events. However, within-class differences and their action on ATP-sensitive potassium channel (KATP) have suggested that second- generation SUs (pancreatic selectivity) are preferable to first generation.

Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SUs should remain a part of the global diabetes treatment portfolio.