Oral Antidiabetic Agents - Luzimar Teixeira

Oral Antidiabetic Agents 387
haemoglobin (HbA1c) concentration, supplemented in some patients by self
monitoring of capillary blood glucose. The average glucose-lowering effect of the
major classes of oral antidiabetic agents is broadly similar (averaging a 1–2%
reduction in HbA1c), α-glucosidase inhibitors being rather less effective. Tailoring
the treatment to the individual patient is an important principle. Doses are
gradually titrated up according to response. However, the maximal glucose-lowering
action for sulphonylureas is usually attained at appreciably lower doses
(approximately 50%) than the manufacturers’ recommended daily maximum.
Combinations of certain agents, for example a secretagogue plus a biguanide or a
thiazolidinedione, are logical and widely used, and combination preparations are
now available in some countries. While the benefits of metformin added to a
sulphonylurea were initially less favourable in the UKPDS, longer-term data have
allayed concern. When considering long-term therapy, issues such as tolerability
and convenience are important additional considerations.
Neither sulphonylureas nor biguanides are able to appreciably alter the rate of
progression of hyperglycaemia in patients with type 2 diabetes. Preliminary data
suggesting that thiazolidinediones may provide better long-term glycaemic stability
are currently being tested in clinical trials; current evidence, while encouraging,
is not conclusive.
Delayed progression from glucose intolerance to type 2 diabetes in high-risk
individuals with glucose intolerance has been demonstrated with troglitazone,
metformin and acarbose. However, intensive lifestyle intervention can be more
effective than drug therapy, at least in the setting of interventional clinical trials.
No antidiabetic drugs are presently licensed for use in prediabetic individuals.
In 1998, the results of the randomised, multicen- management plan that encompasses effective treattre
UKPDS (United Kingdom Prospective Diabetes ment of hypertension and dyslipidaemia; [2-6] both
Study) [1] provided firm evidence of the importance are commonly encountered in patients with type 2
of long-term glycaemic control in middle-aged patients
with newly diagnosed type 2 diabetes mellitus.
Table I. Summary of main results of UKPDS (United Kingdom
Compared with dietary manipulation alone,
Relative
Prospective Diabetes Study) glycaemic control study.
risk (RR) reductions in clinical endpoints for patients randomised to
intensified therapy in the form of oral antidiabetic intensive (i.e. sulphonylurea or insulin) vs conventional therapy (i.e.
agents or insulin significantly reduced the development
of microvascular complications (table I). [1]
diet)
Endpoints RR for Confidence Log-rank
intensive interval
This knowledge drives current clinical practice, in
p-value
therapy
which treatment is directed to the attainment of
Aggregate endpoints b
near-normoglycaemia, i.e. glycosylated haemoglobin
Diabetes-related endpoints 0.88 0.79, 0.99 0.029
(HbA1c) concentrations of 6.5–7.0%. [2-4] Microvascular complications 0.75 0.60, 0.93 0.0099
While such targets may be perceived as being unrealistic
for many – perhaps most – patients, there is
Single endpoints
Sudden death 0.54 0.24, 1.21 0.047
a broad consensus that chronic hyperglycaemia Retinal photocoagulation 0.71 0.53, 0.96 0.0031
should be managed as well as is possible, weighing Cataract extraction 0.76 0.53, 1.08 0.046
safety and quality-of-life considerations on an individual
basis. It is important to bear in mind that
a 95% Confidence interval for aggregate endpoints; 99%
confidence interval for single endpoints.
glycaemic control is just one aspect of an overall
b As defined and ascertained in UKPDS 33. [1]
© 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)