Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

Abstract

The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia®) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of physiological effects generated by GLP-1, which consist of increased insulin secretion, inhibition of glucagon secretion, and decreased gastrointestinal motility alongside the promotion of satiety. In the GetGoal study program, lixisenatide demonstrated significant reductions in glycated hemoglobin (HbA1c), and fasting and postprandial plasma glucose compared with placebo. The effect on glycemia was evident, with both monotherapy and in combination with insulin and various oral antidiabetic agents. Furthermore, a general trend towards reduced bodyweight was reported. In head-to-head trials with the other GLP-1 receptor agonists (exenatide and liraglutide) on the market, lixisenatide demonstrated a superior effect with respect to reduction in postprandial plasma glucose and had a tendency towards fewer adverse events. However, lixisenatide seemed to be less efficient or at best, equivalent to exenatide and liraglutide in reducing HbA1c, fasting plasma glucose, and bodyweight. The combination of a substantial effect on postprandial plasma glucose and a labeling with once daily administration separates lixisenatide from the other GLP-1 receptor agonists. The combination of basal insulin, having a lowering effect on fasting plasma glucose, and lixisenatide, curtailing the postprandial glucose excursions, makes sense from a clinical point of view. Not surprisingly, lixisenatide is undergoing clinical development as a combination product with insulin glargine (Lantus®). At present the main place in therapy of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome.

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

“…To overcome this problem, GLP-1 analogues resistant to degradation by DPP-IV have been developed by three different strategies. The first strategy exploits a naturally occurring protein, exendin-4 (originally isolated from the saliva of the lizard Heloderma suspectum), which activates GLP-1R with equal potency as native GLP-1 [exenatide (Faludi et al, 2009) and lixisenatide (Petersen and Christensen, 2013)]. The second strategy exploits the structure of native GLP-1, with a few amino acid alterations that protect the molecule from being degraded by DPP-IV (taspoglutide; Dong et al, 2011).…”

GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus: Recent Developments and Emerging Agents

“…It is highly selective for GLP‐1, leading to glucose‐dependent insulin secretion and suppression of prandial glucagon production. Lixisenatide reaches peak concentrations after 1–2 hours and has an elimination half‐life of 2–4 hours . Because of its shorter duration of action, it has been studied primarily as a postprandial agent, possibly as a treatment option for patients who cannot achieve glycemic control despite treatment with basal insulin (as previously discussed).…”

“…Lixisenatide reaches peak concentrations after 1-2 hours and has an elimination half-life of 2-4 hours. 34 Because of its shorter duration of action, it has been studied primarily as a postprandial agent, possibly as a treatment option for patients who cannot achieve glycemic control despite treatment with basal insulin (as previously discussed). Lixisenatide was approved for use in the European Union by the European Medicines Agency in February 2013.…”

Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists

“…26 During a 52-week extension of the GetGoal-F1 study in patients uncontrolled on metformin, lixisenatide maintained glycemic control at week 76. Mean HbA1c was reduced from baseline by −0.9%, and body weight decreased by >3 kg 27.…”