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GLP-1 analogues - liraglutide

Liraglutide is the only human GLP-1 analogue currently available. It is
produced by recombinant DNA technology in a species of yeast (Sac-
charomyces cerevisiae). The amino acids that form the backbone of
33
liraglutide are genetically engineered to have a small fatty-acid chain,
which renders the peptide more resistant to degradation by the DPP-4
enzyme, allowing it to act for longer in the body. 34
Liraglutide has a good efficacy and tolerability profile, but currently it is
only indicated for use in combination with metformin and/or a SU when
these oral therapies fail to provide adequate glycaemic control. Lira-
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glutide is administered once daily by subcutaneous injection into the
abdomen, upper thigh or arm, at any time of the day, regardless of
when meals are eaten.
33
The adverse events associated with liraglutide are commonly gastro-
intestinal in nature, although hypoglycaemia, pancreatitis, headache,
dizziness and thyroid problems have also been encountered, albeit
rarely. 33
Liraglutide is degraded by endogenous peptidase and does not have
a renal clearance. A small study evaluated the pharmacokinetics,
safety and tolerability in patients with a wide range of renal function,
from normal to ESRD; there was no association between renal status
and exposure to the active drug or side effects. Thus, no specific dose
adjustment is needed in CKD. Nevertheless, it is not recommended for
use in patients with stage 3 CKD or above, due to a lack of experience
with this product in these patients (Table 1). 33

Amylin analogues

Pramlintide is the only amylin analogue available. It mimics the effects
of the amylin produced by the pancreatic β-cells, namely, slowing gas-
tric emptying and suppressing the secretion of glucagon, the hormone
that opposes the effects of insulin. 35
Because it is a hormone, pramlintide has to be administered via sub-
cutaneous injection prior to meals. Common adverse events associated
35
with the use of pramlintide include nausea, hypoglycaemia, vomiting,
headache, abdominal pain, weight loss and fatigue. 35

For those patients with a GFR of <20 ml/min/1.73 m no dose adjustment
2
of pramlintide is required (Table 1). However, there is a lack of clinical
experience in patients with more severe renal impairment; therefore
pramlintide is not recommended in these patient populations (Table 1). 5

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