Page 48 - 51 the significance--29.2_opt

Due to their novel mode of action, the main adverse events associ-
ated with the use of AGIs are gastrointestinal in nature and include
flatulence, diarrhoea, abdominal pain, nausea, vomiting and indiges-
tion. Less commonly encountered adverse events include liver function
problems, oedema, blood disorders and allergic skin reactions.
29
With respect to their use in diabetic kidney disease, AGIs and their met-
abolites may result in hepatic damage; however, the relevant mecha-
nisms have not been elucidated. For this reason, this drug class is not
30
recommended for patients with a serum creatinine >2 mg/dl (Table 1). 5
GLP-1 mimetics - exenatide

Exenatide is the only GLP-1 mimetic. This product is a synthetic version
of a hormone found in the venom of the gila monster lizard. Exenatide
31
binds to the same cellular receptor as GLP-1 and therefore elicits the
same effects, i.e. stimulation of insulin production and release from the
pancreatic β-cells thereby enhancing glucose uptake by the tissues. 31

Exenatide is administered twice daily by subcutaneous injection into
the skin of the abdomen, thigh, or arm, any time within the 60-minute
period before the first and last meals of the day. Exenatide is effec-
32
tive in reducing HbA , without exposing the patient to the risk of hypo-
1c
glycaemia, and is associated with sustained weight loss. Exenatide is
only indicated for use in combination with metformin and/or a SU when
these oral therapies fail to provide adequate glycaemic control. Ex-
32
enatide adverse events are commonly gastrointestinal in nature, in-
cluding nausea and vomiting. Pancreatitis, headache, and dizziness
have also been encountered, but are rare. 32

Exenatide is eliminated almost entirely by glomerular filtration with
subsequent proteolytic degradation in the kidney. In a small study in
patients with CKD, exenatide was well tolerated in patients with mild-
moderate renal impairment (GFR>30 ml/min), but not in patients with
end stage renal disease (ESRD). Thus the manufacturers recommend
no dose adjustment in patients with Stage 1-2 CKD. In patients with
Stage 3 CKD, dose escalation from 5µg to 10µg should proceed con-
servatively (Table 1). Finally, the manufacturers recommend that ex-
32
enatide is not used in T2DM patients with Stage 4-5 CKD (GFR<30 ml/
min), or those patients on dialysis (Table 1). 32

48