Advances in Therapy

, Volume 30, Issue 2, pp 81–101 | Cite as

Mechanisms and Clinical Efficacy of Lixisenatide for the Management of Type 2 Diabetes

  • Michael HorowitzEmail author
  • Christopher K. Rayner
  • Karen L. Jones
Open Access



“Incretin-based” therapies, such as the glucagon-like peptide-1 (GLP-1) receptor agonists, represent a major advance in type 2 diabetes mellitus (T2DM) treatment. GLP-1 receptor agonists differ substantially in their duration of action, frequency of administration and clinical profile.


This article reviews the mechanisms of action and clinical evidence for GLP-1 receptor targeting and discusses differences between GLP-1 therapies, focusing particularly on clinical data for the GLP-1 receptor agonist, lixisenatide.


GLP-1 therapies target islet cell “defects” of insufficient insulin and excessive glucagon secretion in T2DM, in a glucose-dependent manner, with minimal risk of hypoglycemia. Different GLP-1 therapies exert differential effects on fasting and postprandial glycemia (both being major determinants of glycemic control). They also slow gastric emptying to different extents, probably accounting for different effects to reduce postprandial glycemia. The GetGoal phase 3 studies in T2DM have confirmed the efficacy of once-daily lixisenatide in reducing plasma glucose and glycated hemoglobin (HbA1c), with a pronounced lowering of postprandial plasma glucose (PPG), as monotherapy and as add-on to oral antidiabetic drugs and to basal insulin. Lixisenatide’s ability to diminish PPG is probably partly mediated by its marked ability to delay gastric emptying. Lixisenatide is generally well tolerated, with possibly better gastrointestinal tolerability and lower risk of hypoglycemia than exenatide immediate release. Lixisenatide is associated with a beneficial effect on weight, with either no change or a decrease in body weight when administered as add-on therapy to basal insulin in overweight patients with T2DM.


Lixisenatide improves glycemic control, by primarily affecting PPG, while preventing weight gain or reducing body weight with a low risk of hypoglycemia in T2DM. Lixisenatide is likely to represent a significant advance in the management of T2DM, perhaps particularly in those patients with relatively faster gastric emptying and lower levels of HbA1c, including those receiving basal insulin.


Exenatide Gastric emptying Glucagon-like peptide-1 receptor agonists Hypoglycemia Incretin therapies Liraglutide Lixisenatide Pharmacokinetics Postprandial plasma glucose Type 2 diabetes mellitus 


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© The Author(s) 2013

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Michael Horowitz
    • 1
    • 2
    Email author
  • Christopher K. Rayner
    • 1
    • 2
  • Karen L. Jones
    • 1
    • 2
  1. 1.Discipline of Medicine, Royal Adelaide HospitalUniversity of AdelaideAdelaideAustralia
  2. 2.NHMRC, Centre for Clinical Research Excellence in Nutritional Physiology Interventions and OutcomesUniversity of Adelaide/Royal Adelaide HospitalAdelaideAustralia

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