Add on to insulin EFFICACY AND TOLERABILITY OF GLP1 RECEPTOR AGONISTS AND DPP4 INHIBITORS AS ADDON THERAPY TO INSULIN Complementing Insulin Therapy to Achieve Glycemic Control Anthony H Barnett ID: 657414
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Add on to insulin
EFFICACY AND TOLERABILITY
OF GLP-1 RECEPTOR AGONISTS
AND DPP-4 INHIBITORS AS ADDON THERAPY TO INSULIN
Complementing Insulin Therapy to Achieve Glycemic
Control
Anthony H. Barnett
Adv
Ther
(2013) 30:557–576
Glucagon-like peptide-1 and glucose-
dependentinsulinotropic
polypeptide (GIP) are
incretinhormones
that are secreted into the
circulationby
the intestine in response to nutrient intake.GLP-1 stimulates glucose-dependent
insulinsecretion
, inhibits glucagon secretion,
delaysgastric
emptying, increases feelings of
satiety,and
decreases food intake [82]. GLP-1 and
GIPare
rapidly degraded by the enzyme DPP-4,which exists as both a circulating and
amembrane
-bound form expressed in
manytissues
[82]. In individuals with T2DM, there
isa
decreased response of b-cells to GIP,
whereasthe
insulinotropic
effect of GLP-1 is
nearnormal
[83]. Consequently, efforts have
beendirected
toward enhancing the effect of GLP-1by developing degradation-resistant GLP-1
receptor agonists and inhibitors of DPP-4.Of interest are the findings from some [84,85], but not all studies [86] that a-
glucosidaseinhibitors
may increase GLP-1 release in
healthypeople
as well as in patients with T2DMfollowing a mixed test meal. In
addition,metformin
has been shown to increase
plasmalevels
of GLP-1 after an oral glucose load
inobese
individuals without T2DM and inpatients with T2DM [87, 88]. The
contributionof
this effect to the
antihyperglycemic
efficacy
of these drugs is not clear.