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Diabetes Management Lixisenatide – A New Glucagon-like Peptide 1 Receptor Agonist in the Treatment of Type 2 Diabetes Josep Vidal Head, Endocrinology and Nutrition Department, Hospital Clinic, Barcelona, Spain Abstract Optimal glycaemic control is essential to managing risks in patients with type 2 diabetes. However, glycaemic control remains poor among type 2 diabetes patients, particularly the control of post-prandial glucose (PPG). Almost half of patients treated with basal insulin and oral anti-diabetic drugs (OADs) do not achieve their glycated haemoglobin (HbA 1c ) goals, despite achieving fasting plasma glucose (FPG) control. Glycaemic control targets have emphasised FPG targets, but PPG contributes significantly to overall glycaemic control in type 2 diabetes. Glucagon-like peptide 1 (GLP-1) receptor agonists have shown substantial efficacy in improving overall glycaemic control but have differing effects on PPG, which is a result of their different mechanisms of action. Lixisenatide is unique among existing GLP-1 receptor agonists in that it is short acting but given as a once daily dose, and exerts its main effects during the prandial period. It has demonstrated efficacy in an extensive clinical trial programme. In particular, it has shown a beneficial effect on PPG compared with existing GLP-1 receptor agonists, probably a result of its effect on slowing gastric emptying. This has provided a strong rationale for its use as add-on therapy to long-acting basal insulin analogues, in cases where the latter is not providing adequate glycaemic control. The additive effects on glycaemic control may lead to a new treatment approach to manage blood glucose and prevent long-term complications in patients with type 2 diabetes. Keywords Diabetes, GLP-1 receptor agonist, lixisenatide, post-prandial glucose Disclosure: The author has no conflicts of interest to declare. Acknowledgements: Editorial Assistance was provided by Katrina Mountfort at Touch Medical Media. Received: 5 June 2013 Accepted: 15 July 2013 Citation: European Endocrinology, 2013;9(2):76–81 Correspondence: Josep Vidal, Head, Endocrinology and Nutrition Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. E: jovidal@clinic.ub.es Support: The publication of this article was funded by Sanofi. The views and opinions expressed are those of the author and not necessarily those of Sanofi. The total number of people with diabetes worldwide is projected to rise from 366 million in 2012 to 552 million in 2030. 1 Optimal glycaemic control is essential to managing risks in patients with type 2 diabetes as lower glycaemic exposure is associated with a 25  % reduction in the risk of microvascular complications. 2 However, despite improved therapies and medical care, glycaemic control remains poor among a large proportion of type 2 diabetes patients. 3 Historically, glycaemic control targets have emphasised fasting plasma glucose (FPG) targets, but post-prandial increases in blood glucose contribute significantly to overall glycaemic control in type 2 diabetes. Recent findings suggest that 40–50  % of patients treated with basal insulin and oral diabetic drugs do not achieve their glycated haemoglobin (HbA 1c ) goals, despite achieving FPG control. 4 Importantly, the post-prandial state is the norm for most patients; the true fasting state typically exists only in the 2  hours before breakfast for those who consume three meals a day at relatively regular intervals. Thus, post-prandial glucose (PPG) is increasingly becoming recognised as a therapeutic target for optimising glycaemic control in type 2 diabetes. In recent years, recommendations for type 2 diabetes have reflected increased awareness of the importance of PPG control: the International Diabetes Federation in Europe recommends a PPG target of ≤7.5 mmol/l. 5 76 Admittedly, debate persists over the relative importance of FPG and PPG. 6 It has been suggested that setting targets for PPG is unrealistic and even unsafe because they may increase the risk of hypoglycaemia. 7 However, recommendations on PPG control are supported by a considerable body of scientific data. The majority of patients with type 2 diabetes have elevated PPG, even when HbA 1c is satisfactory (<7  %). 8 Another study found elevated post-challenge plasma glucose (a surrogate of PPG) in 74 % of individuals with type 2 diabetes. 9 Finally, PPG has been shown to independently predict incident cardiovascular disease (CVD) in subjects with type 2 diabetes. 10 A study of patients with type 2 diabetes found that as patients move towards their glycaemic target, the relative importance of targeting FPG versus PPG changes. 11 FPG levels have a greater impact in those with poor glycaemic control whereas PPG levels make a greater contribution to HbA 1c levels in patients with better glycaemic control. For example, at HbA 1c levels of <7.3  % PPG contribute around 70  % of the HbA 1c . However, at HbA 1c levels exceeding 10.2  %, FPG contributes 70  % of the value, and PPG contributes the remaining 30  %. Worsening diabetes control is preceded by changes in daytime post-prandial control, followed by changes during the morning, and finally by changes in nocturnal fasting control. 12 These findings may explain the limited ability of patients to achieve HbA 1c goals even when © Touch ME d ica l ME d ia 2013