‘Efficacy of GLP-1 Receptor Agonists’ in Hypertriglyceridemia: A Systemic Review and Meta Analysis

Abstract

Aims: Hypertriglyceridemia, a prevalent lipid disorder linked to cardiovascular disease and metabolic complications, arises from genetic, lifestyle, or secondary factors like diabetes and obesity. While lifestyle changes and conventional treatments help, many patients need alternative therapies. Glucagon-like peptide-1 receptor agonists, initially for type 2 diabetes, have shown lipid-lowering effects through delayed gastric emptying and enhanced insulin sensitivity. Emerging evidence suggests liraglutide and semaglutide may significantly reduce triglycerides. This meta-analysis evaluates their efficacy in lowering triglycerides across randomized controlled trials, highlighting their potential as adjunct therapy. Study Design: Meta Analysis as per PRISMA guidelines. Place and Duration of Study: Department of Medicine, Bangladesh Institute of Laser and Cell Surgery Hospital, Dhaka, Bangladesh between 2022- 2024. Methodology: This study aimed to evaluate the impact of GLP-1 receptor agonists (GLP-1 RAs) on triglyceride (TG) levels. A comprehensive search in PubMed, Embase, and Cochrane Library identified relevant randomized controlled trials (RCTs) published between 2022 and 2024. Fifteen RCTs (n = 3,450) involving patients with obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and polycystic ovary syndrome (PCOS) met the inclusion criteria. Studies included adults (≥18 years) with TG >150 mg/dL and compared GLP-1 RAs to placebo or lipid-lowering agents with ≥12-week follow-up. The primary outcome was the mean percentage change in TG levels, with secondary outcomes including total cholesterol, LDL, HDL, and body weight. Statistical analysis used a random-effects model, and heterogeneity was assessed using Cochran’s Q test and I² statistics. Subgroup analyses evaluated TG reduction in specific populations, including obese patients, T2DM, NAFLD, PCOS, and those with baseline TG >250 mg/dL. Sensitivity analyses tested the robustness of findings. Studies involving patients on lipid-lowering therapies (e.g., statins, fibrates) were also included, with subgroup analyses assessing their impact. Results: Fifteen RCTs (n = 3,450) evaluated GLP-1 RAs for TG reduction. Semaglutide (5 studies), Liraglutide (4), Dulaglutide (3), and Exenatide (3) were assessed over 12–104 weeks. GLP-1 RAs significantly reduced TG by -19.2% (95% CI: -22.8 to -15.6, p < 0.001) vs. placebo. Greater reductions occurred in obese (-22.1%), T2DM (-20.3%), NAFLD (-21.5%), and PCOS (-18.4%) patients. Higher baseline TG (>250 mg/dL) showed a greater mean reduction (-24.1%). Semaglutide had the greatest reduction (-22.5%), followed by Liraglutide (-20.1%), Dulaglutide (-18.7%), and Exenatide (-16.9%). Moderate heterogeneity (I² = 48%) was noted, and sensitivity analysis confirmed result consistency. Findings support GLP-1 RAs as effective TG-lowering therapy, especially in metabolic conditions. Conclusion: GLP-1 RAs significantly lower triglycerides, making them a valuable option for hypertriglyceridemia, particularly in patients with metabolic syndrome. Semaglutide provides the greatest TG reduction but has higher gastrointestinal side effects, while Liraglutide offers better tolerability. Individualized therapy is key, balancing efficacy and adherence. The dual benefit of GLP-1 RAs in lipid and glycemic control highlights their role in cardiometabolic risk reduction. Further research should explore long-term cardiovascular benefits and combination therapies to optimize treatment.