Effect of Glucagon-like Peptide-1 Receptor Agonists on Lipid Profiles Among Type 2 Diabetes: A Systematic Review and Network Meta-analysis

Abstract Purpose The goal of this study was to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on lipid profiles in patients with type 2 diabetes. Methods The MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from inception through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional antidiabetic drugs with a duration ≥8 weeks. The weighted mean difference for changes in lipid profiles was estimated by using the random effects model, and a network meta-analysis was performed to supplement direct comparisons. Findings Thirty-five trials with 13 treatments were included in the analysis. GLP-1 RAs decreased HDL-C with a range of –0.06 mmol/L (95% CI, –0.11 to –0.01) to –0.13 mmol/L (95% CI, –0.17 to –0.10) compared with thiazolidinediones, whereas thiazolidinediones were associated with a significant increase in HDL-C compared with placebo (0.09 mmol/L [95% CI, 0.06 to 0.12]). A significant reduction in LDL-C was detected for all GLP-1 RAs versus placebo (range, –0.08 to –0.16 mmol/L), insulin (range, –0.10 to –0.19 mmol/L), and thiazolidinediones (range, –0.16 to –0.24 mmol/L). Exenatide, liraglutide 1.8 mg once daily, and taspoglutide decreased total cholesterol with a range of –0.16 mmol/L (95% CI, –0.26 to –0.06) to –0.27 mmol/L (95% CI, –0.41 to –0.12) versus placebo and thiazolidinediones (range, –0.26 to –0.37 mmol/L). The decreased effect was more evident in exenatide long-acting release and liraglutide 1.8 mg once daily. A significant reduction in triglyceride levels was observed with liraglutide 1.8 mg once daily (–0.30 mmol/L [95% CI, –0.49 to –0.11]) and taspoglutide 20 mg once weekly (–0.17 mmol/L [95% CI, –0.31 to –0.01]) versus placebo. Implications GLP-1 RAs were associated with modest reductions in LDL-C, total cholesterol, and triglycerides but no significant improvement in HDL-C. Further evidence is needed to determine if improvements in lipid profiles might translate into reductions in cardiovascular outcomes.