The Effectiveness of GLP-1 Analogue Therapy for Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Introduction: A substantial proportion of type 2 diabetes patients do not maintain effective glycemic control despite the availability of various types of treatments, thus, resulting in the development of micro-vascular and macro-vascular diabetic complications. One new approach that may yield promising results is the use of injectable glucagon-like peptide 1 (GLP-1) analogues, exenatide and liraglutide. Objectives: To assess the effectiveness of GLP-1 analogues in patients with type 2 diabetes mellitus based on randomized controlled trials. Methods: Studies were identified by searching MEDLINE, PubMed, the Cochrane Library, EMBASE, Google Scholar and the main electronic journals. RCTs were selected if they had duration of at least 12 weeks, compared GLP-1 analogues with placebo or other diabetes treatment, and measured HbA1c levels in adult patients with type 2 diabetes mellitus. Meta-analyses were conducted in regard to glycemic control, change in body weight, and risk of hypoglycemia. Results: Fifteen RCTs that met the inclusion criteria were identified. The meta-analysis showed that GLP-1 analogues lowered HbA1c level in comparison to placebo (weighted mean difference -1.15%, 95% confidence interval (CI) from -1.36% to -0.95% at P < 0.00001). GLP-1 analogues resulted in weight loss versus other comparator groups (placebo, oral hypoglycemic agents, and insulin) (weighted mean difference -2.08 kg; 95% CI -3.19 kg to -0.98 kg in favor of GLP-1 analogues at P = 0.0002). The meta-analysis also demonstrated an increased risk of hypoglycemia (which was mainly mild to moderate) with GLP-1 analogues in comparison to placebo (risk ratio 2.79; 95% CI 1.64 to 4.75 at P = 0.0002). Additionally, results from individual studies showed that GLP-1 analogues lowered fasting plasma glucose and post-prandial glycemia, improved pancreatic beta-cell function, and resulted in an increased risk of mild to moderate nausea. Conclusion: GLP-1 analogues are an effective and safe option for glycaemic control in patients with type 2 diabetes mellitus based on findings of the meta-analysis conducted by the author and the results from the individual RCTs included in this systematic review. Nevertheless, continued evaluation of these agents in longer term, high-quality trials is still required before widespread use of these medications.