C H A P T E R 3 8
Agents to control blood glucose levels
587
with the body’s glucose controls in a number of ways,
including affecting insulin release, decreasing insulin
resistance or altering glucose absorption from the GI
tract and release of glucose by the liver. They often are
combined with a sulfonylurea to increase glycaemia
control.
S
ulfonylureas
The
sulfonylureas
bind to potassium channels on pan-
creatic beta cells. They may improve insulin binding
to insulin receptors and increase the number of insulin
receptors. They are also known to increase the effect
of antidiuretic hormone on renal cells. They are effec-
tive only in people who have functioning beta cells.
They are not effective for all diabetics and may lose
their effectiveness over time with others. Sulfonylureas
are further classified as first-generation or second-
generation sulfonylureas. All of the sulfonylureas can
cause hypoglycaemia.
First-generation sulfonylureas
The first-generation sulfonylureas included chlorpropa-
mide and tolbutamide. However, these drugs are no
longer used in Australia and New Zealand.
The first-generation sulfonylureas were associated
with an increased risk of cardiovascular disease and
death in a somewhat controversial study. They are now
thought to possibly cause an increase in cardiovascular
deaths.
Second-generation sulfonylureas
The second-generation drugs include glibenclamide
(
Daonil
,
Gliben
,
Glimel
and others), gliclazide (
Dia-
micron, Glyade
), glimepiride (
Amaryl
) and glipizide
(
Melizide
,
Minidiab
). See Table 38.3 for usual indica-
tions for each drug. Second generation sulfonylureas
have several advantages over the first generation drugs,
including the following:
• They are excreted in urine and bile, making them
safer for individuals with renal dysfunction.
• They do not interact with as many protein-bound
drugs as the first-generation drugs.
• They have a longer duration of action, making it
possible to take them only once or twice a day, thus
increasing compliance.
Glimepiride is a much less expensive drug than most of
the other sulfonylureas, which has advantages for some
people. Prescribers may try different agents (first- or
second-generation drugs) before finding the one that is
most effective for a given person.
Therapeutic actions and indications
The sulfonylureas stimulate insulin release from the beta
cells in the pancreas (see Figure 38.3). They improve
TABLE 38.3
DRUGS IN FOCUS Other oral hypoglycaemic agents (continued)
Drug name
Dosage/route
Usual indications
Other oral hypoglycaemic agents (continued)
Incretin mimetic
exenatide (Byetta)
5 mcg by SC injection within 60 minutes
before morning and evening meals; may be
increased to 10 mcg b.d. after 1 month
Adjunct to diet and oral agents to improve
glycaemic control in people with type 2
diabetes
Sodium-glucose co-transporter inhibitors
canagliflozin (Invokana)
100–300 mg/day PO
Adjunct to diet and exercise to improve
glucose control in people with type 2
diabetes, as monotherapy or combined
with other agents
dapagliflozin (Forxiga)
10 mg/day PO
Adjunct to diet and exercise to improve
glucose control in people with type 2
diabetes, as monotherapy or combined
with other agents
Thiazolidinediones
pioglitazone (Actos)
15–30 mg/day PO as a single dose; use
caution with hepatic impairment
Adjunct to diet to lower blood glucose
in type 2 diabetes; in combination with
insulin or sulfonylureas to control blood
sugar in people whose diabetes cannot
be controlled with either drug alone
rosiglitazone (Avandia)
4–8 mg/day PO as a single dose; use caution
with hepatic impairment
Adjunct to diet to lower blood glucose
in type 2 diabetes; in combination with
insulin or sulfonylureas to control blood
sugar in people whose diabetes cannot
be controlled with either drug alone
