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Sensitisers

Biguanides

Metformin, the only biguanide currently available, is the gold-standard
antidiabetic agent, and is typically the first-line drug therapy in T2DM
patients when exercise or diet intervention have failed to achieve ad-
equate glycaemic control. This compound decreases hepatic gluco-
19
neogenesis and increases the uptake of glucose by the peripheral tis-
sues, especially the skeletal muscle (Figure 3). 15

Metformin is widely used because of its effectiveness, good tolerability
profile and low cost. It is commonly the basis for second- and third-line
combination therapies. Taken up to three times a day, with or after
15
a meal. Typical adverse events associated with the use of metformin
19
include: nausea, vomiting, diarrhoea, abdominal pain, loss of appe-
tite, (these often diminish after the initial stages of treatment), metallic
taste, reduced absorption of vitamin B12, lactic acidosis, allergic skin
reaction, general allergic reaction and liver function problems. 19

Metformin does not exhibit the risk of hypoglycaemia associated with
some of the other drug classes used to treat T2DM. However, special
care must be taken when it is used in patients with CKD. There is an
increased risk of lactic acidosis, even in patients with mild impairment
of kidney function, which is likely due to the accumulation of the drug
and its metabolites. Metformin is contraindicated in male patients
20
with a serum creatinine >1.5 mg/dl and in female patients with serum
creatinine >1.4 mg/dl (Table 1). This concept, however, has recently
5
been challenged by some authors, who suggest its safe treatment op-
tion in patients with stable CKD. 21

Figure 3. The mode of action of metformin.

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