Effects of Insulin Plus Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in Treating Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis

INTRODUCTION Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) has already been proven an efficient treatment option for type 2 diabetes. This combination can effectively improve glycated hemoglobin levels, cause weight loss and reduce the dosage of insulin. In addition, it can also reduce the risk of hypoglycemia. Several randomized controlled trials have confirmed that this treatment may be just as effective for type 1 diabetes mellitus (T1DM) patients. The objective of this meta-analysis was to assess the effects and efficacy of the treatment on glycemic changes, weight loss and insulin dosage in type 1 diabetes mellitus patients. METHODS We searched Embase, PubMed and Cochrane for randomized controlled trials (no time restrictions) that investigated combined insulin and GLP-1 treatment. The main endpoints were measurements of glycated hemoglobin and changes in the weight and the dosage of insulin. RESULTS In total, 1093 were studies identified, and 7 studies were included in our meta-analysis. GLP-1 agonist and insulin combination therapy led to greater reductions in HbA1c levels [P = 0.03; mean difference -0.21; 95% confidence intervals (CI) (-0.40, 0.02)] and weight [P < 0.05; -3.53 (-4.86, 2.19)] compared to control treatments. The combination therapy did not significantly influence the daily weight-adjusted total insulin dose [P = 0.05; -0.11 (-0.23, 0)], but it did reduce the daily weight-adjusted bolus insulin dose [P = 0.001; -0.06 (-0.1, 0.02)]. CONCLUSION Our meta-analysis supports the use of a combined therapeutic regimen of insulin and GLP-1RAs for treating patients with T1DM. Combination therapy with GLP-1 and insulin could achieve an ideal treatment effect on glycemic control, weight loss and bolus insulin dose in patients with T1DM.