LAUSR

BACKGROUND Recent randomized control trials have described a protective cardiovascular effect of novel glucose lowering drugs in patients at high cardiovascular risk. Whether these second-line agents have similar effects in the general population is unknown. We aimed to compare the risk of major cardiovascular and adverse events in new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in T2DM patients not controlled on metformin therapy. METHODS Retrospective cohort study using the MarketScan database (2011-2015). We selected T2DM individuals who were newly dispensed sulfonylureas, SGLT-2i, DPP-4i, or GLP-1a, as second-line therapy, added to metformin. Cohort entry was defined by date of first prescription of the second-line agent. Time to first non-fatal cardiovascular or adverse event was compared using Cox regression models adjusted for confounders. RESULTS Among 118,341 T2DM patients using metformin (mean age: 56), most were at low cardiovascular risk (4% with previous cardiovascular or cerebrovascular event). During a median follow-up of 10 months compared with sulfonylureas users, cardiovascular risk was lower in users of SGLT-2i (aHR = 0.61; 95% CI: 0.40-0.97), DPP-4i (aHR = 0.79; 95% CI: 0.69-0.90) and GLP-1a (aHR = 0.65; 95% CI: 0.48-0.89). Serious adverse events were rare but compared with sulfonylurea, the risk was lower in new users of novel glucose lowering agents. CONCLUSION In our analyses, which included patients with and without prior cardiovascular disease, initiating novel glucose lowering drugs as second-line therapy for T2DM was associated with a lower risk of cardiovascular and adverse events than sulfonylurea initiation.