P2523Cardiovascular risk according to add-on therapy in patients with type 2 diabetes

Abstract

Background: Clinical trials have demonstrated lower risk of cardiovascular events in high-risk patients with type 2 diabetes (T2D) receiving glucagon like peptide 1 (GLP-1) analogues and sodium/glucose transporter 2 (SGLT2) inhibitors. However, whether these drugs are associated with similar benefits in a real world cohort of patients with T2D initiating add-on therapy is unclear. Purpose: To investigate the cardiovascular risk associated with different glucoselowering agents in addition to metformin in a real-world cohort of T2D patients. Method: By use of Danish nationwide health- and administrative registries we included patients with T2D with no prior history of heart failure (HF), myocardial infarction (MI) or stroke, initiating add-on therapy on top of metformin in the period 2010-2016. Patients were grouped according to add-on therapy (dipeptidyl peptidase-4 [DPP-4] inhibitors, GLP-1 analogues, SGLT-2 inhibitors, sulfonylurea or insulin). Patients were followed for up to two years for the outcomes of heart failure (HF) hospitalization, myocardial infarction (MI) or stroke and death. Cox regression models adjusted for age, sex, duration of T2D and comorbidity were used to estimate the risks of outcomes with DPP-4 inhibitors as reference. Results: The study included 46,215 patients with T2D, with a median age of 61 years, 59% men and median duration of T2D of 4.2 years prior to inclusion. A total number of 15,054 (32%) initiated DPP4 treatment, 13,211 (29%) GLP-1, 2,065 (5%) SGLT2, 8,775 (19%) sulfonylurea and 7,110 (15%) insulin. During follow-up 1,753 (4%) died (range across groups 2-9%), 511 (1%) were hospitalized for HF (range 0.5-2%), and 829 (2%) had an MI or a stroke (range 1.0-2.2%). In adjusted Cox regression models with DPP4 group as reference, insulin or sulfonylurea therapy was associated with a higher risk of death and HF hospitalization (only insulin) (Figure). The risk of MI or stroke was lower in patients treated with GLP-1 analogues, and a trend toward a similar reduction in those treated with SGLT inhibitors. Conclusion: In a nationwide cohort of patients with T2D treated with metformin, add-on therapy with insulin and sulfonylurea was associated with higher risk of death compared to DPP-4 inhibitors. GLP-1 analogues and SGLT2 inhibitors were not associated with any significant differences in risk of death or HF hospitalization compared to DPP4 inhibitors; although both drugs appeared to be associated with a lower risk of MI or stroke. Our findings suggest that the guidelines ought to highlight use of newer anti-diabetic therapies.