Abstract 10677: Dapagliflozin in Patients With Type 2 Diabetes and Established Cardiovascular Disease: Hypotension and Volume-related Safety
Background: Dapagliflozin (DAPA), a selective SGLT2 inhibitor that causes increased urinary glucose excretion and mild osmotic diuresis, is a compound for treatment of type 2 diabetes mellitus (T2DM). DAPA 10 mg/d vs placebo (PBO) add-on therapy to usual care was assessed in 2 studies in inadequately controlled T2DM patients (HbA1c 7.0%-10.0%) with established cardiovascular disease (Study [ST] 1: NCT01031680, N=922; ST2: NCT01042977, N=964). Published results showed greater reductions in HbA1c, weight, and systolic blood pressure with DAPA vs PBO and that DAPA was well tolerated over 52 wks. We present volume-related safety results from these studies.
Methods: Patients in both randomized studies received PBO or DAPA 10 mg added to a stable antidiabetic and antihypertensive background regimen. Patients were stratified by age <65 or ≥65 y, insulin use, and time from the most recent qualifying CV event. A prespecified history of hypertension was an inclusion criterion for ST1 and was present in 93% of patients in ST2.
Results: At baseline in ST1 and ST2, mean age was 62.9 and 63.8 y, T2DM duration was 12.4 and 13.2 y, and insulin was used by 52.1% and 60.5% of patients. Incidence of adverse events (AE) was similar between groups (Table) and in both age strata. Few patients had volume-related AEs, AEs of orthostatic hypotension, or hematocrit values >55%. AEs of renal impairment/failure (mostly lab abnormalities), most of which resolved or normalized, occurred more often with DAPA. DAPA patients receiving loop diuretics had similar proportions of AEs and volume-related events as the overall study population. AEs were balanced among groups in patients receiving an ACE inhibitor or ARB and in those with congestive heart failure (CHF).
Conclusion: In T2DM patients, DAPA added to usual care was well tolerated for volume-related AEs with no unexpected findings overall and in subgroup analyses of age strata, patients receiving loop diuretics, ACE inhibitors or ARBs, or CHF patients.
- © 2013 by American Heart Association, Inc.