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Lixisenatide, a novel GLP‐1 receptor agonist: efficacy, safety and clinical implications for type 2 diabetes mellitus

Recent advances in therapies for the treatment of type 2 diabetes mellitus (T2DM) have led to the development of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), which, unlike insulin and sulphonylurea, are effective, with a low risk of hypoglycaemia. Lixisenatide is recommended as a once‐daily GLP‐1 RA for the treatment of T2DM. In persons with T2DM, lixisenatide 20 µg once‐daily given by bolus subcutaneous injection improves insulin secretion and suppresses glucagon secretion in a glucose‐dependent manner. Compared with the longer‐acting GLP‐1 RA liraglutide, lixisenatide achieved a significantly greater reduction in postprandial plasma glucose (PPG) during a standardized test breakfast in persons with T2DM otherwise insufficiently controlled on metformin alone. This is primarily due to the greater inhibition of gastric motility by lixisenatide compared with liraglutide. The efficacy and safety of lixisenatide was evaluated across a spectrum of T2DM in a series of phase III, randomized, placebo‐controlled trials known as the GetGoal programme. Lixisenatide monotherapy or as add‐on to oral antidiabetic agents or basal insulin achieved significant reductions in glycated haemoglobin, PPG and fasting plasma glucose, with either weight loss or no weight gain. The most frequent adverse events were gastrointestinal and transient in nature. Lixisenatide provides an easy, once‐daily, single‐dose, add‐on treatment to oral antidiabetic agents or basal insulin for the management of T2DM, with little or no increased risk of hypoglycaemia and a potential beneficial effect on body weight.