PMID- 23423907
OWN - NLM
STAT- MEDLINE
DCOM- 20131217
LR  - 20221207
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Linking)
VI  - 30
IP  - 2
DP  - 2013 Feb
TI  - Mechanisms and clinical efficacy of lixisenatide for the management of type 2 
      diabetes.
PG  - 81-101
LID - 10.1007/s12325-013-0009-4 [doi]
AB  - 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.
FAU - Horowitz, Michael
AU  - Horowitz M
AD  - Discipline of Medicine, Royal Adelaide Hospital, University of Adelaide, North 
      Terrace, Adelaide, SA, 5000, Australia. michael.horowitz@adelaide.edu.au
FAU - Rayner, Christopher K
AU  - Rayner CK
FAU - Jones, Karen L
AU  - Jones KL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130213
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Blood Glucose)
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 74O62BB01U (lixisenatide)
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Glycated Hemoglobin/drug effects
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Peptides/pharmacology/*therapeutic use
MH  - Receptors, Glucagon/*agonists
MH  - Treatment Outcome
EDAT- 2013/02/21 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/02/21 06:00
PHST- 2012/12/13 00:00 [received]
PHST- 2013/02/21 06:00 [entrez]
PHST- 2013/02/21 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - 10.1007/s12325-013-0009-4 [doi]
PST - ppublish
SO  - Adv Ther. 2013 Feb;30(2):81-101. doi: 10.1007/s12325-013-0009-4. Epub 2013 Feb 
      13.