Influence of Dapagliflozin Dosing on Low-Density Lipoprotein Cholesterol in Type 2 Diabetes Mellitus: A Systematic Literature Review and Meta-Analysis.

A systematic literature review and meta-analysis was performed to evaluate the effects of dapagliflozin on low-density lipoprotein (LDL) cholesterol in type 2 diabetes mellitus. Data on changes in LDL cholesterol, adverse cardiac events (ACEs), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were pooled in a meta-analysis. Data from dose comparison trials were separately pooled, and meta-analysis was conducted by using RevMan (5.4.1) and R (4.1.2). Dapagliflozin increased LDL cholesterol by 2.33 mg/dL (95% CI, 1.46 to 3.19; I = 0%; P < .00001), increased risk of ACEs by 1.56 (95% CI, 1.02 to 2.39; I = 0%; P < .04), decreased HbA1c by -0.41% (95% CI, -0.44 to -0.39; I = 85%; P < .00001), and decreased FBG by -13.51 mg/dL (95% CI, -14.43 to -12.59; I = 92%; P < .00001) versus any placebo or active comparator. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 1.71 mg/dL (95% CI, -1.20 to 4.62; I = 53%; P = .25) versus a 5 mg dose and by 1.04 mg/dL (95% CI, -1.17 to 3.26; I = 62%; P = .36) versus a 2.5 mg dose. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 3.13 mg/dL (95% CI, 1.31 to 4.95; I = 0%; P = .0008), increased the risk of ACEs by 1.26 (95% CI, 0.56 to 2.87; I = 0%; P = .58), decreased HbA1c by -0.4% (95% CI, -0.45 to -0.35; I = 89%; P < .00001), and decreased FBG by -8.39 mg/dL (95% CI, -10 to -6.77; I = 96%; P < .00001) versus a placebo or active comparator. Dapagliflozin monotherapy resulted in a minimal but statistically significantly (P = .0002) increase in LDL cholesterol. However, this minor change does not increase the risk of ACEs (P = .17) when compared with placebo or active comparator.