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

Diabetes Care: May, 2023

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 compared with those without.

In the last decade, large dedicated CV outcome trials in people with type 2 diabetes and at high risk or with established CV disease have shown that dipeptidyl peptidase 4 inhibitors (DPP4i) do not increase CV risk, while sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor analogists (GLP-1RA) reduce CV risk.

As a result, national and international guidelines have favored newer, more expensive glucose-lowering medicines over older, cheaper options such as sulfonylureas (SU) and thiazolidinediones (TZD).


This study analyzed data from a large cohort derived from the entire Scottish population with type 2 diabetes to provide real-world evidence on the cardiovascular safety of sulfonylureas versus other glucose-lowering medications (DPP4 inhibitors and thiazolidinediones), each being used in combination with metformin for treatment intensification.

Data from 31,460 individuals with type 2 diabetes were included in this analysis, comparing sulfonylureas with DPP4 inhibitors/thiazolidinediones.


This study suggests that sulfonylureas are unlikely to increase cardiovascular risk or all-cause mortality.

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

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This is for informational purposes only. You should consult your clinical textbook for advising your patients.