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Mechanisms and clinical efficacy of lixisenatide for the management of type 2 diabetes.
Adv Ther. 2013 Feb; 30(2):81-101.AT

Abstract

INTRODUCTION

"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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Discipline of Medicine, Royal Adelaide Hospital, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia. michael.horowitz@adelaide.edu.auNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23423907

Citation

Horowitz, Michael, et al. "Mechanisms and Clinical Efficacy of Lixisenatide for the Management of Type 2 Diabetes." Advances in Therapy, vol. 30, no. 2, 2013, pp. 81-101.
Horowitz M, Rayner CK, Jones KL. Mechanisms and clinical efficacy of lixisenatide for the management of type 2 diabetes. Adv Ther. 2013;30(2):81-101.
Horowitz, M., Rayner, C. K., & Jones, K. L. (2013). Mechanisms and clinical efficacy of lixisenatide for the management of type 2 diabetes. Advances in Therapy, 30(2), 81-101. https://doi.org/10.1007/s12325-013-0009-4
Horowitz M, Rayner CK, Jones KL. Mechanisms and Clinical Efficacy of Lixisenatide for the Management of Type 2 Diabetes. Adv Ther. 2013;30(2):81-101. PubMed PMID: 23423907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms and clinical efficacy of lixisenatide for the management of type 2 diabetes. AU - Horowitz,Michael, AU - Rayner,Christopher K, AU - Jones,Karen L, Y1 - 2013/02/13/ PY - 2012/12/13/received PY - 2013/2/21/entrez PY - 2013/2/21/pubmed PY - 2013/12/18/medline SP - 81 EP - 101 JF - Advances in therapy JO - Adv Ther VL - 30 IS - 2 N2 - INTRODUCTION: "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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1865-8652 UR - https://www.unboundmedicine.com/medline/citation/23423907/Mechanisms_and_clinical_efficacy_of_lixisenatide_for_the_management_of_type_2_diabetes_ L2 - https://dx.doi.org/10.1007/s12325-013-0009-4 DB - PRIME DP - Unbound Medicine ER -