Type 2 diabetes mellitus (T2DM) is an increasing health problem worldwide. Glucagon-like peptide-1 (GLP-1) receptor agonists are an expanding drug class that target several of the pathophysiological traits of T2DM. Lixisenatide is a GLP-1 receptor agonist in development for once-daily treatment of T2DM.Pharmacological, preclinical and clinical evidence demonstrating the applicability of lixisenatide for the treatment of T2DM are reviewed. Available data and pending clinical development are summarized, critically appraised and compared to competitor drugs. The most relevant papers and meeting abstracts published up to November 2010 are used as sources for this review.Efficacy and safety in T2DM are demonstrated with lixisenatide in monotherapy and in combination with metformin. However, limited data with the intended once-daily 20 μg subcutaneous dosing necessitate further evaluation of lixisenatide as add-on to various antidiabetic treatments. It remains to be established whether the slightly differing chemical properties compared to other GLP-1 receptor agonists including a rather short duration of action will be a disadvantage or maybe even an advantage, for example, when combined with long-acting insulin.