Effects of the glucagon-like peptide-1 and glucagon receptor dual agonists on glycemic markers: A systematic review and meta-analysis of randomized controlled trials

Abstract

Recently, it has been reported that dual agonists of the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor (GCGR) have important functions in regulating glucose metabolism and energy expenditure. However, the usefulness of these dual agonists for the treatment of type 2 diabetes remains unclear. This systematic review and meta-analysis of randomized controlled trials aimed to assess the impact of GLP-1/GCGR dual agonists on glycemic markers. The search process was performed in PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library databases. Randomized controlled trials assessing the impact of GLP-1/GCGR agonists on glycemic parameters were included. The meta-analysis was performed with the random-effects model and the generic inverse variance method, and the leave-one-out method was used for the sensitivity analysis. The meta-analysis of 14 randomized controlled trials demonstrated that GLP-1/GCGR agonists significantly decrease fasting glucose (weighted mean difference (WMD): –0.79 mmol/l, 95% confidence interval (CI): –1.14, –0.45, p < 0.0001, I² = 92%) and glycated hemoglobin (HbA1c; WMD: –0.50%, 95% CI: –0.67, –0.32, p < 0.0001, I² = 93%). However, these dual agonists had no significant impact on insulin levels (WMD: –14.78 pmol/l, 95% CI: –35.89, 6.34, p = 0.17, I² = 87%). The subgroup analysis by treatment duration exhibited that GLP-1/GCGR agonists significantly reduced fasting glucose and HbA1c in randomized controlled trials ≤12 and >12 weeks, as well as insulin levels in those studies >12 weeks of treatment. In conclusion, the results of our meta-analysis indicated that GLP-1/GCGR dual agonists have a positive effect by decreasing fasting glucose and HbA1c concentrations.