C H A P T E R 3 8
Agents to control blood glucose levels
589
development of lactic acidosis. Both acarbose and met-
formin can cause GI distress. Metformin is approved for
use in children 10 years of age and older. It is also being
used in the treatment of women with polycystic ovary
syndrome (see Box 38.7).
The thiazolidinediones (
Actos
and others) are drugs
that decrease insulin resistance; they are used in combi-
nation with sulfonylureas, insulin or metformin to treat
individuals with insulin resistance. The first drug of this
class, troglitazone, was withdrawn from the market after
reports of serious hepatotoxicity. The two drugs that are
available now—pioglitazone and rosiglitazone—are not
associated with the same severe liver toxicity, although in
late 2007 reports were published linking these drugs to
an increase in cardiovascular events. Rosiglitazone was
withdrawn from the New Zealand market in April 2011
due to safety concerns related to increased cardiovasular
risk. People should still be monitored for any change in
liver function while they are taking these drugs. These
drugs are also being studied for use in increasing ovu-
lation frequency in woman who have polycystic ovary
syndrome (Box 38.7). Box 38.8 describes some of the
new fixed combination oral agents, which provide two
different agents in one tablet to make it easier for the
person to be compliant.
Therapeutic actions and indications, pharmaco
kinetics, contraindications and cautions, adverse
effects and clinically important drug–drug interac-
tions for these drugs are basically the same as for the
sulfonylureas. The safety and efficacy of these drugs for
use in children have not been established, except for the
use of metformin in children 10 years of age and older.
The newest of the oral hypoglycaemic agents include:
exenatide, which was released in 2005; the glucagon-like
peptide 1 analogue liraglutide released in 2005; the
DPP-4 inhibitors which first became available in 2007;
and the sodium-glucose co-transporter inhibitors, cana-
gliflozin and dapagliflozin released in 2013.
Exenatide and liraglutide mimic the effects of
GLP-1: leading to enhancement of glucose-dependent
insulin secretion by the beta cells in the pancreas,
depression of elevated glucagon secretion and slowed
gastric emptying to help moderate and lower blood
glucose levels. Exenatide is given by subcutaneous injec-
tion twice a day, within 60 minutes before the morning
and evening meals. It has a rapid onset of action and
peaks within 2 hours; its effects last 8 to 10 hours. It is
given in combination with oral agents to improve glycae-
mic control in type 2 diabetes individuals who cannot
achieve glycaemic control on oral agents alone. It should
not be given if the person is unable to eat. Liraglutide
Polycystic ovary syndrome is an ovarian function
disorder associated with obesity, infrequent or absent
menses and infertility. Women who have this disorder
have elevated insulin levels with normal fasting blood
glucose levels, elevated luteinising hormone (LH) levels,
and normal oestrogen and follicle-stimulating hormone
levels. Because of the alterations in hormone activity,
follicles develop on the ovaries, but ovulation does not
occur, and the developed follicles turn into cysts. The
high LH levels tend to cause an increase in androgen
production, which is associated with insulin resistance.
Treatment is aimed at altering the metabolic changes
to allow ovulation (if pregnancy is desired) or stop
the follicle development (if pregnancy is not desired).
Weight loss is very important and may correct the
alterations in metabolism and allow ovulation to occur
without medical treatment. Metformin and pioglitazone
have proven effective in increasing insulin sensitivity
and decreasing androgen and LH levels to break the
cycle and allow ovulation to occur if pregnancy is
desired. A fertility drug is often used with the oral
hypoglycaemic agent. Hormonal contraceptives are used
if pregnancy is not desired, to halt the development of
the follicles and stop the cyst production.
■■
BOX 38.7
Polycystic ovary syndrome and oral
hypoglycaemic drugs
Several fixed-combination oral hypoglycaemic agents
have become available in the last 5 years. These
combination products are intended to decrease the
number of tablets the person needs to take each day and
thereby increase compliance with the drug regimen. The
person should be stabilised on the individual product
first and then switched to the combination product
after the correct dose combination for that person has
been established. The person should be reminded that
diet and exercise are still the key parts of the diabetes
management regimen.
•
Avandamet
is a combination of rosiglitazone
and metformin and is available in four sizes:
2 mg rosiglitazone with 1000 mg metformin,
2 mg rosiglitazone with 500 mg metformin, 4 mg
rosiglitazone with 1000 mg metformin, 4 mg
rosiglitazone with 500 mg metformin.
•
Galvusmet
is a combination of vildagliptin and
metformin and is available in three sizes:
50 mg vildagliptin with 1000 mg metformin,
50 mg vildagliptin with 500 mg metformin,
50 mg vildagliptin with 850 mg metformin.
•
Glucovance
is a combination of metformin and
glibenclamide and is available in three sizes:
250 mg metformin with 1.25 mg glibenclamide,
500 mg metformin with 2.5 mg glibenclamide,
500 mg metformin with 5 mg glibenclamide.
•
Janumet
is a combination of sitagliptin and metformin
and is available in three sizes: 50 mg sitagliptin with
1000 mg metformin, 50 mg sitagliptin with 500 mg
metformin, 50 mg sitagliptin with 850 mg metformin.
■■
BOX 38.8
Available fixed-combination oral
agents
