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Other incretin therapies

DPP-4 inhibitors are not the only incretin therapies available for the
management of T2DM. Exenatide and liraglutide are two other drugs
that act on the incretin system. Instead of impeding the degradation
of native GLP-1, exenatide mimics GLP-1, whereas as liraglutide is an
analogue of this incretin (both stimulate GLP-1 receptors and, thus, are
GLP-1 receptor agonists). In this section we will compare and contrast
these agents with the DPP-4 inhibitors.

Exenatide is a peptide hormone and a synthetic version of exendin-4, a
hormone found in the saliva of the venomous lizard, the Gila monster.
This hormone is composed of 39 amino acids, of which >50% are the
same as those found in human GLP-1. The actions this drug has on the
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body in terms of glucose homeostasis are very similar to GLP-1. How-
ever, unlike endogenous or human recombinant GLP-1, it is more resis-
tant to being broken down by the DPP-4 enzyme because of its different
molecular structure, thereby extending its duration of action in vivo. 92

Liraglutide is a human GLP-1 analogue produced by recombinant DNA
technology in a species of yeast (Saccharomyces cerevisiae). The
linked amino acids that form the backbone of liraglutide are geneti-
cally engineered so that it bears a small fatty-acid chain, an addition
to the hormone that renders it more resistant to degradation by the
DPP-4 enzyme. This modification extends the half-life of liraglutide in the
body. 93

Differentiating DPP-4 inhibitors from GLP-1 mimetics and
analogues

Administration

Being peptides, both exenatide and liraglutide would be digested in the
GI tract if they were swallowed as an oral formulation; therefore, they
must be administered via subcutaneous injection into the abdomen,
upper thigh or arm. Exenatide must be injected twice a day, whereas
liraglutide only needs to be injected once a day. 94 95 Oral administration
of a drug is more convenient for the patient than an injection and this
route of administration may be a barrier to using exenatide and liraglu-
tide in patients with such preferences.

Efficacy

Both DPP-4 inhibitors and GLP-1 mimetics/analogues differ in their effic-
acy and adverse event profiles. In clinical trials exenatide treatment
was shown to be safe and efficacious. This GLP-1 mimic significantly

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