Abstract 13665: Dapagliflozin Does Not Affect Left Ventricular Remodeling in Patients With Type 2 Diabetes. A Meta-Analysis of Phase IV Randomized Controlled Trials

Abstract

Introduction: Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT-2) inhibitor approved for the treatment of Type-2 DM. Proposed mechanisms for its cardiovascular benefits include natriuresis, reduction in preload and afterload, and improved cardiac metabolism. Hypothesis: Dapagliflozin can reverse left ventricular remodeling in type-2 diabetics. Methods: Systematic review was performed to identify phase IV randomized controlled trials (RCTs) evaluating dapagliflozin vs placebo. Mean Difference (MD) of multiple parameters (along with 95% confidence intervals; CI) was extracted to compute pooled MD using RevMan v.5.3. Random effects model was employed when there was significant heterogeneity (>40%, as assessed by I-squared). Results: Two RCTs were finalized (n=122; dapagliflozin 60, placebo 62). All patients (males 75, females 47) had type-2 DM and were more than 60 years old. Pooled analysis did not show significant difference in left ventricular remodeling with dapagliflozin as compared to placebo; (LV Mass Index reduction (g/m 2 ): MD -0.14, 95% CI -1.12 to 0.85; p=0.78, I 2 =0%). Dapagliflozin reduced systolic (MD -3.66; -7.29 to -0.02; p=0.05, I 2 =0%) and diastolic BP (MD -3.04; -5.75 to -0.32; p=0.03, I 2 =84%). Reduction in weight upto 3.4 kgs (MD -3.42; -4.48 to -2.36; p<0.05, I 2 =59%) and HbA1c up to 3.7% (MD -3.76; -7.35 to -0.17; p=0.04, I 2 =14%) was observed with dapagliflozin. Dapagliflozin use improved hemoglobin (Hb) (MD 1.08; 0.50 to 1.66; p<0.05, I 2 =95%) and hematocrit (Hct) (MD 2.90; 1.99 to 3.80; p<0.05, I 2 =0%). No significant difference in ejection fraction (MD 0.77; -0.97 to 2.51; p=0.87, I 2 =0%), LV End-systolic volume (LV-ESV) (MD -1.02; -3.38 to 1.34; p=0.40, I 2 =0%), LV End-diastolic volume (LV-EDV) (MD -1.08; -6.40 to 4.24; p=0.69, I 2 =0%), stroke volume (SV) (MD 1.19; -1.66 to 4.04; p=0.41, I 2 =0%) and heart rate (MD -2.15; -5.14 to 0.85; p=0.16, I 2 =0%) was seen between two groups. Similarly, no change in creatinine (MD 2.14; -0.53 to 4.82; p=0.12, I 2 =0%) or eGFR (MD -1.34; -5.02 to 2.35; p=0.48, I 2 =24%) was observed. Conclusion: Dapagliflozin had no statistically significant effect on cardiac remodeling. However BP, weight, HbA1c, Hb and Hct improved significantly with dapagliflozin as compared to placebo over one year.