Cardiovascular events with second-line antidiabetic medication

Abstract

1. O’Brien MJ, et al. Association of Second-line Antidiabetic Medications With Cardiovascular events with Cardiovascular Events Among Insured Adults With Type 2 Diabetes. JAMA Network Open 1: e186125, No. 8, 21 Dec 2018. Available from: URL: http:// second-line antidiabetic medication dx.doi.org/10.1001/jamanetworkopen.2018.6125. 2. Callahan A, et al. A Second Opinion From Observational Data on Second-line Some antidiabetic medications (ADMs) used as Diabetes Drugs JAMA Network Open 1: e186119, No. 8, 21 Dec 2018. Available from: URL: http://dx.doi.org/10.1001/jamanetworkopen.2018.6119. second-line treatment appear to be associated with an 803367475 increased risk of cardiovascular events, according to study results reported in JAMA Network Open, particularly sulfonylureas and basal insulin. The retrospective cohort study1 included data collected from the Observational Health Data Sciences and informatics network in the USA between April 2011 and September 2015. The 132 737 adults were included when they initiated treatment with their first ADM other than metformin. The composite primary outcome was hospitalisation for a cardiovascular event, comprising congestive heart failure, ischaemic heart disease, peripheral artery disease or stroke. The most frequently prescribed ADM class was sulfonylureas (including meglitinides; 47.6%), followed by dipeptidyl peptidase-4 (DPP-4) inhibitors (21.8%), basal insulin (12.2%), glucagon-like peptide-1 (GLP-1) receptor agonists (8.6%), thiazolidinediones (TZDs; 5.6%) and sodium-glucose contransporter 2 (SGLT-2) inhibitors (4.3%). During 169 384 person-years of follow-up, 3480 cardiovascular events occurred. Compared with DPP-4 inhibitors, patients treated with sulfonylureas had a significantly increased risk of cardiovascular events (hazard ratio [HR] 1.36; 95% CI 1.23, 1.49). The risk was also significantly increased for basal insulin recipients (HR 2.03; 1.81, 2.27). The numbers needed to harm during 2 years of treatment were 103 and 37, respectively. There was no significantly increased risk for SGLT-2 inhibitor recipients (HR 0.81; 0.57, 1.53) or TZD recipients (HR 0.92; 0.76, 1.11). The authors note that the recent introduction of SGLT-2 inhibitors led to relatively little data for this medication, and therefore including longer follow-up in this group may have increased statistical power to detect significant cardiovascular benefits from these medications . The risk was significantly lower for GLP-1 receptor recipients (HR 078; 0.63, 0.96), although the authors note that this finding was not significant in all sensitivity analyses . There was a significant reduction in stroke risk for GLP-1 receptor recipients (HR 0.65; 0.44, 0.97). Collectively, these findings raise concerns about the cardiovascular safety of sulfonylureas and basal insulin compared with newer ADMs , note the authors, and suggest that short-term cardiovascular outcomes of newer ADM classes may be similar among patients starting second-line treatment . In an accompanying commentary reported in JAMA Network Open,2 Alison Callahan and Nigam Shah (Stanford University School of Medicine) note that largescale observational studies like these make it possible to investigate the efficacy of an ever-growing pool of treatments and their associated risks of adverse outcomes . However, they add that the increasing ease of conducting such studies with these large data sources makes it essential both to conduct rigorous analyses and to make the details of these analyses transparent , and that clinical researchers need to adopt good practices in the analyses of observational data . 1