Oral Antidiabetic Agents - Luzimar Teixeira

Oral Antidiabetic Agents 393
be monitored by periodic measurement of HbA1c (or nylurea therapy generally has modest effects on
fructosamine if HbA1c is not available).
blood lipid profiles, although some studies have
noted a small decrease in plasma triglyceride levels
1.1.4 Efficacy – possibly linked to improved glycaemic control –
The blood glucose-lowering efficacy of sulpho- and minor increments in high-density lipoprotein
nylureas has been evaluated in many retrospective (HDL)-cholesterol. When a sulphonylurea is used in
and prospective studies, and from decades of collec- combination with another antidiabetic agent, the
tive worldwide clinical experience. When used as glucose-lowering efficacy of the sulphonylurea is
monotherapy in patients inadequately controlled by approximately additive to the effect of the other
nonpharmacological measures, sulphonylureas can agent. Once again, response is crucially dependent
be expected to reduce fasting plasma glucose by an on the presence of adequate β-cell function. Early
average of 2–4 mmol/L accompanied by a decrease use of such combination therapy is indicated when
in HbA1c of 1–2%. [4,19,21] However, individual re- optimal titration of a single agent does not achieve
sponses are variable. Since the hypoglycaemic ef- adequate glycaemic control.
fect of sulphonylureas is attributable to increased The combination of two different types of agents
insulin secretion, the effectiveness of these drugs is is more likely to achieve glycaemic targets, albeit
dependent on adequate β-cell function. The afore- for a variable period of time. If combination therapy
mentioned progressive β-cell failure that determines is started at a stage when hyperglycaemia is already
the natural history of type 2 diabetes may require an marked (after ‘failure’ of monotherapy), then β-cell
increased dosage of sulphonylureas if glycaemic depletion is likely to be advanced. Under these
control deteriorates. Rapid and uncontrollable dete- circumstances, oral combination therapy is likely to
rioration of glycaemic control during sulphonylurea offer limited benefit and the need for an early move
therapy is sometimes termed ‘secondary sulphony- to insulin treatment is usually clear. Since there are
lurea failure’. This phenomenon, which is some- occasional exceptions to this rule, a limited trial of
thing of a misnomer, occurs in approximately combination oral therapy may be worthwhile. How-
5–10% of patients per annum with suggestions of ever, the temptation to procrastinate unduly on
differences in ‘failure’ rates between some com- transferring the patient to insulin treatment should
pounds. [21,22] The inability to maintain acceptable be firmly resisted, not least since some patients
glycaemic control is common to all sulphonylureas derive rapid symptomatic benefit from insulin therand
is held to reflect an advanced stage of β-cell apy. Impending metabolic decompensation, with or
failure, that is, it is a reflection of disease progres- without ketosis, mandates immediate insulin treatsion
rather than a true failure of therapy. Individuals ment; more severe degrees of decompensation, for
who have greater degrees of β-cell reserve usually example obtundation, dehydration, ketosis-assorespond
well to sulphonylureas; early use of sulpho- ciated vomiting, necessitates emergency hospitalisanylureas
as first-line monotherapy in these patients tion for treatment with intravenous insulin, fluids
will produce better blood glucose lowering than late and electrolytes.
intervention in patients with severely compromised
β-cell function.
1.1.5 Adverse Events
The plasma insulin concentrations achieved Hypoglycaemia, usually subclinical or minor but
during sulphonylurea therapy do not usually extend occasionally life threatening, is the most common
beyond the range observed in the general non-diabe- and potentially most serious adverse effect of sultic
population (including those with impaired glu- phonylurea therapy. [23] Patients receiving sulphocose
tolerance), and suggestions that sulphonylurea- nylureas should receive instruction on the recogniinduced
hyperinsulinaemia might increase the risk tion and prevention of hypoglycaemia and the
of detrimental insulin-induced effects on the cardio- prompt actions they must take should warning
vascular system remain unsubstantiated. [12] Sulpho- symptoms develop. Severe protracted hypogly-
© 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)