Oral Antidiabetic Agents - Luzimar Teixeira

398 Krentz & Bailey
2.3 Indications and Contraindications breast-feeding are traditionally regarded to be contraindications
for all oral antidiabetic drugs, mainly
An α-glucosidase inhibitor may be used as because of a lack of safety data rather than evidence
monotherapy for patients with type 2 diabetes that is of detrimental effects.
inadequately controlled by nonpharmacological
measures. Because α-glucosidase inhibitors target 2.4 Efficacy
postprandial hyperglycaemia, they can be a useful
An α-glucosidase inhibitor can reduce peak confirst-line
treatment in patients who have a combinacentrations
of blood glucose and reduce interprandition
of only slightly raised basal glucose concentraal
troughs. Used as monotherapy to patients who
tions and more marked postprandial hyperglycomply
appropriately with dietary advice, an α-
caemia. A recent multicentre clinical trial (STOPglucosidase
inhibitor will typically reduce postpran-
NIDDM [Study TO Prevent NonInsulin-Dependent
dial glucose concentrations by 1–4 mmol/L. The
Diabetes Mellitus]) confirmed the utility of acarbose
incremental area under the postprandial plasma gluin
preventing the transition from impaired glucose
cose curve can be more than halved in some individtolerance
to diabetes [32] (see section 2.4). Acarbose
uals. There seems to be a ‘carry-over’ effect that
can be used in combination with other antidiabetic
may produce a reduction in basal glycaemia up to
agents. When starting therapy with an α-glucosidase
1 mmol/L. The decrease in HbA1c is usually about
inhibitor it is said to be important to ensure that the
0.5–1.0%, provided that a high dose of the drug is
patient is taking a diet rich in complex carbohytolerated
and dietary compliance is maintained.
drates, as opposed to simple sugars. Acarbose
[33]
There may be a trivial alteration in the gastrointestishould
be taken with meals, starting with a low dose,
nal absorption of other oral antidiabetic agents when
for example 50 mg/day, and slowly titrating up over
used in combination therapy. In general, the extra
several weeks. Monitoring of glycaemic control,
benefit to glycaemic control achieved by addition of
particularly postprandially, may be helpful. The
an α-glucosidase inhibitor to another antidiabetic
postprandial action of these agents would not be
agent is additive. In the recently published multicenexpected
to induce hypoglycaemia, at least when
tre STOP-NIDDM trial acarbose reduced the risk of
they are used as monotherapy. The maximum dosprogression
from impaired glucose tolerance to type
age of α-glucosidase inhibitors may be limited by
2 diabetes (relative hazard 0.75; 95% CI 0.63, 0.90;
gastrointestinal symptoms; this is certainly our exp
= 0.0015). [32] This study randomised 1429 patients
perience with acarbose (see section 2.5). Intuitively,
with impaired glucose tolerance to acarbose 100mg
patients experiencing gastrointestinal adverse efthree
times daily or placebo, of whom data were
fects with metformin may not be the best candidates
available for a modified intention-to-treat analysis
in whom to add an α-glucosidase inhibitor. A hisin
1368 patients. Glucose tolerance was determined
tory of chronic intestinal disease serves as a – largeusing
a 75g oral glucose tolerance test. Intriguingly,
ly theoretical – contraindication to acarbose and
new cases of hypertension and major cardiac events,
other agents in this class. High dosages of acarbose
including overt and clinically silent myocardial incan
occasionally increase liver enzyme concentrafarction,
were also reduced by acarbose therapy.
tions, and it is recommended that transaminase con-
[34]
The latter were not primary endpoints of the study, a
centrations are measured at intervals in patients relimitation
acknowledged by the investigators.
ceiving the maximum dosage (200mg three times
[34]
The results of ongoing trials using acarbose and
daily in the UK, a dosage rarely attained in practice
other agents in this class are awaited.
for the aforementioned reasons). If liver enzymes
[35]
are raised, the dosage of acarbose should be reduced
to a level at which normal enzyme concentrations
2.5 Adverse Effects
are re-established. Alternative causes of hepatic dys- The most common problems with α-glucosidase
function should be considered. Pregnancy and inhibitors are gastrointestinal adverse effects. In the
© 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)