Novel glucose lowering agents are associated with a lower risk of cardiovascular and adverse events in type 2 diabetes: A population based analysis

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 the date of the 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 a 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