Document Detail


The pharmacologic basis for clinical differences among GLP-1 receptor agonists and DPP-4 inhibitors.
MedLine Citation:
PMID:  22104467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The incretin system plays an important role in glucose homeostasis, largely through the actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Unlike GIP, the actions of GLP-1 are preserved in patients with type 2 diabetes mellitus, which has led to the development of injectable GLP-1 receptor (GLP-1R) agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1R agonists-which can be dosed to pharmacologic levels-act directly upon the GLP-1R. In contrast, DPP-4 inhibitors work indirectly by inhibiting the enzymatic inactivation of native GLP-1, resulting in a modest increase in endogenous GLP-1 levels. GLP-1R agonists generally lower the fasting and postprandial glucose levels more than DPP-4 inhibitors, resulting in a greater mean reduction in glycated hemoglobin level with GLP-1R agonists (0.4%-1.7%) compared with DPP-4 inhibitors (0.4%-1.0%). GLP-1R agonists also promote satiety and reduce total caloric intake, generally resulting in a mean weight loss of 1 to 4 kg over several months in most patients, whereas DPP-4 inhbitors are weight-neutral overall. GLP-1R agonists and DPP-4 inhibitors are generally safe and well tolerated. The glucose-dependent manner of stimulation of insulin release and inhibition of glucagon secretion by both GLP-1R agonists and DPP-4 inhibitors contribute to the low incidence of hypoglycemia. Although transient nausea occurs in 26% to 28% of patients treated with GLP-1R agonists but not DPP-4 inhibitors, this can be reduced by using a dose-escalation strategy. Other adverse events (AEs) associated with GLP-1R agonists include diarrhea, headache, and dizziness. The main AEs associated with DPP-4 inhibitors include upper respiratory tract infection, nasopharyngitis, and headache. Overall, compared with other therapies for type 2 diabetes mellitus with similar efficacy, incretin-based agents have low risk of hypoglycemia and weight gain. However, GLP-1R agonists demonstrate greater comparative efficacy and weight benefit than DPP-4 inhibitors.
Authors:
Javier Morales
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Postgraduate medicine     Volume:  123     ISSN:  1941-9260     ISO Abbreviation:  Postgrad Med     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-22     Completed Date:  2012-01-23     Revised Date:  2012-03-15    
Medline Journal Info:
Nlm Unique ID:  0401147     Medline TA:  Postgrad Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  189-201     Citation Subset:  AIM; IM    
Affiliation:
Advanced Internal Medicine Group, PC, New Hyde Park, NY, USA. saxodoc@optonline.net
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MeSH Terms
Descriptor/Qualifier:
Blood Glucose / drug effects*,  metabolism
Body Weight / drug effects
Diabetes Mellitus, Type 2 / drug therapy*
Dipeptidyl-Peptidase IV Inhibitors / adverse effects,  pharmacology*,  therapeutic use
Drug Hypersensitivity
Glucagon-Like Peptide 1 / adverse effects,  analogs & derivatives,  pharmacology,  therapeutic use
Homeostasis / drug effects
Humans
Hypoglycemic Agents / adverse effects,  pharmacology*,  therapeutic use
Incretins / metabolism
Pancreatitis / chemically induced
Peptides / adverse effects,  pharmacology,  therapeutic use
Receptors, Glucagon / agonists*
Venoms / adverse effects,  pharmacology,  therapeutic use
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Dipeptidyl-Peptidase IV Inhibitors; 0/Hypoglycemic Agents; 0/Incretins; 0/Peptides; 0/Receptors, Glucagon; 0/Venoms; 0/glucagon-like peptide receptor; 0/liraglutide; 141732-76-5/exenatide; 89750-14-1/Glucagon-Like Peptide 1
Comments/Corrections
Erratum In:
Postgrad Med. 2012 Jan;124(1):177-8

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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