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Secretagogues

Sulphonylureas (SUs)

SUs are a mainstay in T2DM treatment. They trigger insulin release by
binding to ATP-dependent potassium channels on pancreatic β-cells
(Figure 2). 14 15 They are administered orally, once, twice or three times a
day shortly before a meal. 14 15
This class of antidiabetics is divided into first, second and third genera-
tion types; however the first generation SUs (e.g. chloropropamide and
tolbutamide) are rarely used today. 14 15 The second and third genera-
tion SUs (e.g. glibenclamide, gliclazide, glipizide and glimepiride) are
more commonly prescribed, as they offer improved efficacy and toler-
ability. 14 15

SUs are widely used to treat T2DM and are often combined with met-
formin alone or, more rarely, metformin and a thiazolidinedione (TZD),
especially in those patients where metformin alone fails to provide ad-
equate glycaemic control. 14 15
Typical adverse events associated with the use of SUs include hypo-
glycaemia, weight gain, nausea, vomiting, diarrhoea, constipation, loss
of appetite, abdominal pain, bloating, indigestion, liver function prob-
lems, blood disorders, allergic skin reactions, etc. 14 15

The clearance of any SU and its metabolites is highly dependent on
kidney function, and severe prolonged episodes of hypoglycaemia as
a result of SU use have been described in dialysis patients. In patients
16
with Stage 3–5 CKD, first-generation SUs should be avoided (Table 1).
Of the newer generation SUs, glipizide is recommended because it is
metabolised into inactive metabolites by the liver and then excreted
by the kidney, and consequently there is a lower risk of hypoglycaemia
(Table 1).
5
Meglitinides

Only two meglitinides are available (repaglinide and nateglinide) and
they work in a similar way to SUs, except they bind to a different site on
the ATP-dependent potassium channel (Figure 2). The net effect is an
increase in insulin secretion, although they have a shorter duration of
action than SUs. 15

Meglitinides are taken orally up to three times a day with, or not longer
than 30 minutes before, meals. They are often used in combination
15
with metformin. Meglitinides are generally better tolerated than SUs
15
and typical adverse events associated with these agents include hypo-

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