In patients with type 2 diabetes (T2D), incretin-based therapies improve glycaemic control with low incidence of hypoglycaemia and without weight gain, both advantages over traditional add-ons to metformin. Dipeptidyl peptidase-4 (DPP-4) inhibitors are administered orally and provide a physiological increase in glucagon-like peptide-1 (GLP-1) levels, while GLP-1 receptor agonists (GLP-1RAs) are injectable and deliver pharmacological levels of GLP-1RA. This review aims to distinguish between GLP-1RAs and DPP-4 inhibitors, and discuss when each may be favoured in clinical practice.


A MEDLINE search, limited to human clinical trials and using the search criteria ‘GLP-1RA’ or ‘DPP-4 inhibitor’, identified seven head-to-head studies and one relevant post hoc analysis (all a GLP-1RA vs. the DPP-4 inhibitor sitagliptin). In combination with treatment algorithms, product prescribing information and personal clinical experience, these studies were used to compare the efficacy and suitability of GLP-1RAs and DPP-4 inhibitors in patients with T2D.


In head-to-head clinical trials, GLP-1RAs provided greater glycaemic control, weight loss and overall treatment satisfaction vs. the DPP-4 inhibitor sitagliptin. Transient nausea was more frequent with GLP-1RAs and should be addressed through patient education and an incremental dosing approach. Current treatment algorithms recommend incretin-based therapy use after metformin failure, but local guidance may restrict their use.


GLP-1RAs provide superior glycaemic control and weight loss vs. DPP-4 inhibitors in patients with T2D. DPP-4 inhibitors may sometimes be preferred to a GLP-1RA if weight is not a concern, oral administration is a desirable feature or when a GLP-1RA cannot be tolerated.