Efficacy of glucagon-like peptide-1 receptor agonists compared to dipeptidyl peptidase-4 inhibitors for the management of type 2 diabetes: A meta-analysis of randomized clinical trials

Aims: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are both incretin-based therapies for type 2 diabetes (T2DM) but have distinct efficacy and side effect profiles. We thus performed a systematic review and meta-analysis to compare the effects of GLP-1 agonists to DPP-4 inhibitors on glycaemic control, weight and incidence of adverse events in adults with T2DM. We also sought to determine whether there was any additional effect in switching from DPP-4 inhibitor to GLP-1 agonist. Materials and methods: We systematically searched PubMed, Embase and for (1) randomized controlled trials (RCTs) comparing any GLP-1 agonist to any DPP-4 inhibitor and (2) interventional studies where a DPP-4 inhibitor was switched to a GLP-1 agonist. We assessed pooled data using random-effects model (CRD42017057115). Results: The pooled analysis of 13 RCTs (n = 4330) showed that, compared to DPP-4 inhibitors, GLP-1 agonists yielded a greater mean reduction in glycated haemoglobin (HbA1c) of -0.41% (95% CI -0.53 to -0.30) and in weight of -2.15 kg (-3.04 to -1.27). GLP-1 agonists were associated with greater likelihood of gastrointestinal side effects with no increased risk of hypoglycaemia. In 5 interventional studies (n = 433), switching from DPP-4 inhibitor to GLP-1 agonist yielded further mean reduction in HbA1c of -0.69% (-1.03 to -0.35) and in weight of -2.25kg (-3.12 to -1.38). Conclusions: GLP-1 agonists yield greater reduction in HbA1c and weight as compared to DPP-4 inhibitors, with increased incidence of gastrointestinal symptoms but not hypoglycaemia. Replacing a DPP-4 inhibitor with GLP-1 agonist provides additional benefits in glycaemic control and weight loss.