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Thiazolidinediones (TZDs)

The TZDs rosiglitazone and pioglitazone are currently available for the
treatment of T2DM. The use of rosiglitazone in the treatment of T2DM has
been marred by a meta-analysis, which demonstrated an increased
risk of myocardial infarction (significant) and death from cardio-
vascular causes (borderline significance) in patients receiving this TZD.
22
For these reasons, its use has been discontinued in Europe.
TZDs bind to a peroxisome proliferator-activated receptor γ (PPAR γ) on
the cell nucleus, eliciting a variety of effects, the net result of which is a
decrease in insulin resistance allowing more glucose to enter the cells.
15
TZDs are taken once or twice daily with or without food and they are
often used in combination with metformin or metformin plus another
antidiabetic drug, such as a SU. 23 24

Typical adverse events include, weight gain oedema, heart failure,
blood disorders, increase in blood lipids, increased appetite, increased
risk of bone fractures (women), and visual disturbances. 23 24

Of considerable interest is the suggestion that TZDs may prevent or slow
the progression of kidney disease in people with T2DM independently
of glycaemic control. Several small studies have reported a greater
25
reduction in albuminuria in patients administered TZDs. However, there
8
has been no evidence to support an independent association be-
tween TZD use and actual prevention of diabetic kidney disease. TZDs
have been demonstrated to be effective without increasing the risk
of hypoglycaemic episodes in patients with CKD, including those re-
ceiving dialysis, 12 26 27 and in patients who require therapy for glycaemic
control after a kidney transplant. As TZDs undergo hepatic metabo-
28
lism, no adjustment in dosing is required in any stage of CKD, or for those
patients on dialysis or who have had a kidney transplant (Table 1). One
8
concern, however, of using TZDs in T2DM patients with renal impairment
is that the risk of fluid retention and heart failure may be exacerbated ;
8
thus they should be used with caution in patients with CKD. Neverthe-
less, fluid retention can be adequately controlled by diuretics.
Alpha-glucosidase inhibitors (AGIs)

Acarbose, miglitol and voglibose are the currently available AGIs. In
contrast to the other anti-diabetic agents, AGIs have no effect on in-
sulin secretion or sensitivity, as they are essentially non-systemic. These
15
compounds inhibit enzymes in the small intestine that are responsible
for breaking down carbohydrates into monosaccharides, thereby re-
ducing the amount of monosaccharides, namely glucose that are
transported through the intestinal wall into the bloodstream. AGIs are
15
taken three times a day with the first mouthful of food.
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