Oral Antidiabetic Agents - Luzimar Teixeira

408 Krentz & Bailey
by many tissues, albeit at a low level, we must await
the verdict of time for any unforeseen effects of
long-term stimulation with thiazolidinediones. For
example, PPARγ activation in macrophages can reduce
the production of some inflammatory cytokines
and might increase transformation of monocytes
to macrophages in the vascular wall. Stimulation
of PPARγ in colon cells has been variously
reported to increase and decrease division and
differentiation of these cells in different animals and
cell models; [69] thus, familial polyposis coli is a
contraindication to thiazolidinediones on theoretical
grounds.
4. Summary and Conclusion
The management of patients with type 2 diabetes
has been given a firm evidence base in recent years
through the results of randomised clinical trials,
notably the UKPDS. An improved understanding of
the pathogenesis and natural history of this complex
metabolic disorder has facilitated the application of
new therapeutic agents. Attainment and maintenance
of near-normal glycaemic control, while
minimising the risk of iatrogenic hypoglycaemia, is
a central long-term objective of therapy; however,
this is often difficult to achieve in practice.
The following general principles should be ap-
plied while using oral antidiabetic drugs.
• Antidiabetic drug therapy must be considered
carefully within the context of the overall care
plan. This includes an assessment of which agent
is most likely to achieve the therapeutic goals of
the care plan, taking account of the accompanying
medical and lifestyle circumstances and commitments
of the patient.
• Always check for contraindications.
• For some classes of agents, e.g. sulphonylureas,
duration of action and route of elimination will be
important considerations if hypoglycaemia is
likely, or if renal or liver disease raises concerns.
Shorter-acting preparations are preferred for
those at risk of hypoglycaemia and in the elderly.
• Start with the lowest recommended dose and
monitor response taking the mode of action into
account. Sulphonylureas generally produce a rap-
id improvement in glycaemic control (within
days), whereas the maximal response to thiazoli-
dinediones may take several weeks to become
apparent. Maximal glucose-lowering effects are
usually obtained at doses lower than the manu-
facturer’s recommendations, e.g. 5–10 mg/day
for glibenclamide.
• If the glycaemic target is not achieved consider
adding another class of agent at an early stage.
Undertake the same evaluation and titration pro-
cedure for the second agent. If a combination of
two oral agents does not give adequate control,
there may be some patients who will benefit from
addition of a third differently acting oral therapy.
Compliance generally deteriorates as the daily
number of doses increases.
• Inability to achieve adequate glycaemic control
with a logical combination of oral therapies is
likely to indicate that the natural history of the
disease has progressed to a state of severe β-cell
failure. In this situation it is usually necessary to
switch to insulin therapy. Similarly, failure to
respond to an oral agent (so-called primary fail-
ure) or loss of control (secondary failure) usually
reflects a severe degree of insulin deficiency and
early need for insulin. All oral antidiabetic agents
are contraindicated in type 1 diabetes and in
major metabolic decompensation. Insulin may be
required temporarily during intercurrent severe
illness.
Clinicians have a greater range of antidiabetic
treatments to choose from than ever, but this has
brought a new level of complexity to management.
In addition, polypharmacy has become the norm for
many patients with type 2 diabetes in recognition of
the importance of treating hypertension and dyslipidaemia,
both commonly encountered and modi-
fiable cardiovascular risk factors. The main classes
of oral antidiabetic drugs are broadly similar in their
glucose-lowering capacity, at least in the short- to
medium term. [70] Accordingly, the most appropriate
therapy should be selected according to the clinical
and biochemical characteristics of the patient, safety
considerations always being a major consideration.
The UKPDS has influenced prescribing in the UK
© 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)