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

Abstract 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 2 = 0%; P < .00001), increased risk of ACEs by 1.56 (95% CI, 1.02 to 2.39; I 2 = 0%; P < .04), decreased HbA1c by −0.41% (95% CI, −0.44 to −0.39; I 2 = 85%; P < .00001), and decreased FBG by −13.51 mg/dL (95% CI, −14.43 to −12.59; I 2 = 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 2 = 53%; P = .25) versus a 5 mg dose and by 1.04 mg/dL (95% CI, −1.17 to 3.26; I 2 = 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 2 = 0%; P = .0008), increased the risk of ACEs by 1.26 (95% CI, 0.56 to 2.87; I 2 = 0%; P = .58), decreased HbA1c by −0.4% (95% CI, −0.45 to −0.35; I 2 = 89%; P < .00001), and decreased FBG by −8.39 mg/dL (95% CI, −10 to −6.77; I 2 = 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.