Lixisenatide (Lyxumia(®)) is a glucagon-like peptide-1 receptor agonist that acts in a glucose-dependent manner to improve glycemic control in adult patients with type 2 diabetes mellitus. Subcutaneous once-daily prandial lixisenatide is indicated for the treatment of adult patients with type 2 diabetes to achieve glycemic control in combination with oral antihyperglycemic drugs (OADs) and/or basal insulin when these antihyperglycemic drugs do not provide adequate glycemic control. In an extensive phase III clinical trial program, lixisenatide once daily in combination with OADs and/or basal insulin for 24 weeks improved glycemic control, had beneficial effects on bodyweight, and was generally well tolerated in adult patients with inadequately controlled type 2 diabetes despite treatment with OADs and/or basal insulin. At 24 weeks, in terms of the primary efficacy endpoint of each trial, combination therapy with lixisenatide was associated with better efficacy than placebo in patients inadequately controlled on OADs and/or basal insulin, was shown to be noninferior to exenatide in patients inadequately controlled on background metformin therapy, and showed similar efficacy to sitagliptin in patients inadequately controlled on background metformin therapy. Further clinical experience/post-marketing surveillance studies and long-term safety data, along with pharmacoeconomic analyses, are required to fully define the position of lixisenatide in relation to other antihyperglycemics. In the meantime, once-daily prandial lixisenatide in combination with OADs and/or basal insulin (plus diet and exercise) is an effective option for improving glycemic control in adult patients with type 2 diabetes, including in patients where bodyweight loss is an essential component in their management.