medwireNews: Findings from a Scottish national cohort study show that the use of sulfonylureas (SUs) as second-line glucose-lowering therapy is not associated with elevated cardiovascular (CV) risk or all-cause mortality.
For the study, Ewan Pearson (University of Dundee, UK) and co-authors included data for 29,518 adults with type 2 diabetes diagnosed before the end of 2017, who did not reach a glycated hemoglobin level of 48 mmol/mol (6.5 %) or lower despite receiving metformin monotherapy and were started on SUs (62.8%) or non-SUs (37.2%) as second-line therapy in 2010 or later.
During a median follow-up of 3.9 and 3.0 years in the SU and non-SU groups, respectively, the unadjusted incidence rates of major adverse CV events (MACE), defined as hospitalization for myocardial infarction, ischemic stroke, or heart failure, and CV death, were higher in the SU than non-SU group, at 23.4 versus 18.7 per 1000 person–years. Similar results were observed for the individual MACE endpoints.
However, when the researchers calculated the relative effect of SUs versus non-SUs in analyses accounting for confounding variables including prescribing preferences, they obtained adjusted hazard ratios ranging from 0.96 to 1.03. They note that the upper limits of the 95% confidence intervals, which were all below 1.3, met the criteria for noninferiority of SUs versus non-SUs.
Writing in Diabetes Care they say that “SUs prescribed as second-line pharmacotherapy are unlikely to increase CV risk.”
The team also looked at subgroup analyses comparing SUs versus dipeptidyl peptidase (DPP)-4 inhibitors (n=9114) and versus thiazolidinediones (TZD; n=1873). The results of the multivariable analysis showed no significantly higher risks in the SU group compared with DPP-4 inhibitors and TZD. And they add that “[t]he CV safety of SU was consistently supported across all predefined subgroups.”
Pearson et al conclude: “Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.”
Diabetes Care 2023; doi: 10.2337/dc22-1238