Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Advertise | Login 
 
Search Article 
  
Advanced search 
  Users Online: 321 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size  
REVIEW ARTICLE
Year : 2014  |  Volume : 18  |  Issue : 6  |  Page : 753-759

Dipeptidyl peptidase-4 inhibitors: Novel mechanism of actions


Senior Consultant Endocrinologist, G. D. Diabetes Hospital, Kolkata, West Bengal; Sun Valley Diabetes Hospital, Guwahati, Assam, India

Correspondence Address:
Dr. Awadhesh Kumar Singh
Flat-1C, 3 Canal Street, Kolkata - 700 014, West Bengal
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2230-8210.141319

Rights and Permissions

The pharmacological actions of the glucagon-like peptide-1 receptor agonists (GLP-1RA) are largely predictable as they interact directly with GLP-1 receptors on beta cells to mediate their glucose lowering effects by increasing GLP-1 in pharmacological range and not at all dependent upon endogenous GLP-1 secretion. The mechanism of action of dipeptidyl peptidase-4 inhibitors (DPP-4I) are relatively less clear although classical mechanism is to inhibit the endogenous GLP-1 metabolism and thereby increasing GLP-1 level in the physiological range. DPP-4I also increase the half-life of GLP-1 to some extent by inhibiting their quick degradation by DPP enzyme ubiquitously present in the body. Interestingly, even with the effective blockade with currently existing DPP-4I, the half-life of GLP-1 only increases from 1 min to 5 min and therefore its residual time in plasma still remains pretty short. Intriguingly, this GLP-1 rise is so modest and so short-lived that it may be difficult to believe that this would sufficiently engage and activate the GLP-1 receptor in beta cell to produce significant insulinotropic effect. However, in clinical trials as well as in real life scenario, the anti-glycemic efficacies seen with DPP-4I are quite satisfactory and sometime very much competitive to GLP-1RA as evident from their head-to-head trials including meta-analysis. This efficacy outcome challenges the "only" GLP-1 dependent mechanism of glucose lowering and provokes an insight that other neuro-endocrine pathway may be playing a second fiddle. This review will collate those emerging concept and put a perspective as to how DPP-4I might be working though other pathway besides direct GLP-1 mediated receptor activation.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed3476    
    Printed47    
    Emailed1    
    PDF Downloaded1043    
    Comments [Add]    
    Cited by others 25    

Recommend this journal