Cardiorenal outcomes with ertugliflozin assessed according to baseline glucose‐lowering agent: An analysis from VERTIS CV

AIM: To assess selected cardiorenal outcomes with ertugliflozin according to use of baseline glucose‐lowering agent. MATERIALS AND METHODS: VERTIS CV was a cardiovascular (CV) outcome trial for ertugliflozin versus placebo, conducted in patients with type 2 diabetes and established atherosclerotic CV disease. The primary outcome was time to the first event of CV death, myocardial infarction or stroke (major adverse CV events [MACE]), with other CV outcomes also assessed. Outcomes were analysed using Cox proportional hazards models stratified by baseline use of metformin, insulin, sulphonylureas (SUs) and dipeptidyl peptidase‐4 (DPP‐4) inhibitors, with interaction testing to assess for treatment effect modification. Changes from baseline in glycaemic, metabolic and haemodynamic variables were also assessed. RESULTS: Of 8246 randomized patients, at baseline 6286 (76%) were on metformin, 3898 (47%) were on insulin, 3383 (41%) were on SUs and 911 (11%) were on DPP‐4 inhibitors, alone or in combination therapy (67% used >1 glucose‐lowering agent at baseline). For each glucose‐lowering agent evaluated, no evidence for effect modification was observed for MACE by baseline use of metformin (with: hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.790, 1.073; without: 1.13, 95% CI 0.867, 1.480), insulin (with: HR 0.91, 95% CI 0.765, 1.092; without: 1.06, 95% CI 0.867, 1.293), SUs (with: HR 1.11, 95% CI 0.890, 1.388; without: 0.90, 95% CI 0.761, 1.060) or DPP‐4 inhibitors (with: HR 0.77, 95% CI 0.502, 1.173; without: 1.00, 95% CI 0.867, 1.147) (all P (interaction) > 0.05). Similar results were observed for all secondary outcomes analysed. CONCLUSION: In VERTIS CV, the effects of ertugliflozin on cardiorenal outcomes were consistent across subgroups of patients stratified by baseline glucose‐lowering agent. ClinicalTrials.gov identifier: NCT01986881