Sulfonylureas, compared with DPP-4 inhibitors and thiazolidinediones, were not associated with excess risk for adverse CV events.

For patients with type 2 diabetes and inadequate glycaemic control who receive metformin monotherapy, sulfonylureas are an inexpensive add-on treatment. However, concerns about their cardiovascular (CV) safety are one reason for their declining use.

Using a national registry of all patients with type 2 diabetes, researchers in Scotland identified 20,000 patients (age range, 40 to 85 years) who added sulfonylureas to metformin between 2010 and 2017. Their CV outcomes were compared with those of 10,000 patients who added dipeptidyl peptidase-4 (DPP-4) inhibitors and 2000 who added thiazolidinediones. To address potential confounding in this observational study, the researchers used both conventional multivariable analyses and an additional tool called ‘instrumental variable analysis.’

During median follow up of about four years, the three groups had no significant differences in major adverse CV events, components of that endpoint (i.e. CV-related death and hospitalisation for myocardial infarction, stroke or heart failure) or all-cause mortality.

Comment: This population-based study is consistent with randomised trials that showed similar CV outcomes with sulfonylurea add-on therapy (mainly glimepiride) compared with DPP-4 inhibitors, glargine insulin or pioglitazone (NEJM JW Gen Med Nov 15 2019 and JAMA 2019; 322: 1155-1166; NEJM JW Gen Med Dec 1 2017 and Lancet Diabetes Endocrinol 2017; 5: 887-897; NEJM JW Gen Med Oct 15 2022 and N Engl J Med 2022; 387: 1075-1088). Therefore, the authors conclude that ‘[sulfonylureas] should remain as part of the global diabetes treatment portfolio.’ This conclusion seems reasonable for patients with low CV risk and normal renal function. For patients at high CV risk, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists are the preferred add-on therapies; however, their costs in the USA are extraordinarily high compared with sulfonylureas, and many uninsured or underinsured patients cannot afford them. Finally, keep in mind the potential adverse effects of sulfonylureas – hypoglycaemia and weight gain.

Allan S. Brett, MD, Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.

Wang H, et al. Cardiovascular safety in type 2 diabetes with sulfonylureas as second-line drugs: a nationwide population-based comparative safety study. Diabetes Care 2023; 46: 967-977.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Hospital Medicine.