PMID- 22104467
OWN - NLM
STAT- MEDLINE
DCOM- 20120123
LR  - 20181201
IS  - 1941-9260 (Electronic)
IS  - 0032-5481 (Linking)
VI  - 123
IP  - 6
DP  - 2011 Nov
TI  - The pharmacologic basis for clinical differences among GLP-1 receptor agonists 
      and DPP-4 inhibitors.
PG  - 189-201
LID - 10.3810/pgm.2011.11.2508 [doi]
AB  - 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.
FAU - Morales, Javier
AU  - Morales J
AD  - Advanced Internal Medicine Group, PC, New Hyde Park, NY, USA. 
      saxodoc@optonline.net
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Postgrad Med
JT  - Postgraduate medicine
JID - 0401147
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Incretins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (Venoms)
RN  - 839I73S42A (Liraglutide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
EIN - Postgrad Med. 2012 Jan;124(1):177-8
MH  - Blood Glucose/*drug effects/metabolism
MH  - Body Weight/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*pharmacology/therapeutic use
MH  - Drug Hypersensitivity
MH  - Exenatide
MH  - Glucagon-Like Peptide 1/adverse effects/analogs & 
      derivatives/pharmacology/therapeutic use
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Homeostasis/drug effects
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/*pharmacology/therapeutic use
MH  - Incretins/metabolism
MH  - Liraglutide
MH  - Pancreatitis/chemically induced
MH  - Peptides/adverse effects/pharmacology/therapeutic use
MH  - Receptors, Glucagon/*agonists
MH  - Venoms/adverse effects/pharmacology/therapeutic use
EDAT- 2011/11/23 06:00
MHDA- 2012/01/24 06:00
CRDT- 2011/11/23 06:00
PHST- 2011/11/23 06:00 [entrez]
PHST- 2011/11/23 06:00 [pubmed]
PHST- 2012/01/24 06:00 [medline]
AID - 10.3810/pgm.2011.11.2508 [doi]
PST - ppublish
SO  - Postgrad Med. 2011 Nov;123(6):189-201. doi: 10.3810/pgm.2011.11.2508.