Oral Antidiabetic Agents - Luzimar Teixeira
Oral Antidiabetic Agents - Luzimar Teixeira
Oral Antidiabetic Agents - Luzimar Teixeira
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402 Krentz & Bailey<br />
Princeton, NJ, USA) 1 and elsewhere (although not secretion. Indeed, the reduction of basal insulin conin<br />
the UK). A combined rosiglitazone/metformin centrations, notably in hyperinsulinaemic patients,<br />
(Avandamet ® , GlaxoSmithKline, Philadelphia, PA, should itself improve insulin sensitivity by relieving<br />
USA) [see section 3.2] preparation is also available the insulin-induced downregulation of insulin recepin<br />
some parts of the world.<br />
tor number and suppression of post-receptor insulin<br />
During long-term treatment with metformin it is pathways. [35] Bodyweight tends to stabilise or deadvisable<br />
to check (e.g. annually) for the developprovements<br />
crease slightly during metformin therapy. Small imment<br />
of contraindications, particularly an elevated<br />
in the blood lipid profile may be observ-<br />
serum creatinine concentration (yearly measurement ed in hyperlipidaemic patients; plasma concentra-<br />
of creatinine clearance posing practical difficulties). tions of triglycerides, fatty acids and low-density<br />
Metformin can reduce gastrointestinal absorption of lipoprotein (LDL)-cholesterol tend to fall, whereas<br />
cyanocobalamin (vitamin B12). While anaemia is cardioprotective HDL-cholesterol tends to rise.<br />
very rare, an annual haemoglobin measurement is These effects appear to be independent of the antiprudent<br />
in patients at risk of nutritional deficiencies. hyperglycaemic effect, although a lowering of trig-<br />
It is advised to stop metformin treatment temporariinsulin<br />
lyceride and free fatty acids is likely to help improve<br />
ly during use of intravenous radiographic contrast<br />
sensitivity and benefit the glucose-fatty acid<br />
media, surgery and any other intercurrent situation cycle.<br />
in which the exclusion criteria could be invoked. [46] In the UKPDS, overweight patients who started<br />
Substitution with insulin may be appropriate at such oral antidiabetic therapy with metformin showed a<br />
times. Metformin alone is unlikely to cause serious statistically significant 39% reduced risk of myocarhypoglycaemia,<br />
but hypoglycaemia becomes an is- dial infarction compared with conventional treatsue<br />
when metformin is used in combination with an ment (p = 0.01). [47] No clear relationship is evident<br />
insulin-releasing agent or insulin.<br />
between metformin dosage and decreased coronary<br />
artery events. This suggests that patients who can<br />
3.1.4 Efficacy only tolerate a low dosage of metformin may benefit<br />
The long-term blood glucose-lowering efficacy from continuing the drug, even when other agents<br />
of metformin is broadly similar to sulphonylureas. have to be added to optimise glycaemic control. The<br />
As monotherapy in patients who are not adequately decrease in myocardial infarction observed with<br />
controlled on nonpharmacological therapy, optimal- metformin therapy in the UKPDS was not attributaly<br />
titrated metformin therapy typically reduces fast- ble to more effective lowering of HbA1c or major<br />
ing plasma glucose by 2–4 mmol/L, corresponding effects on classic cardiovascular risk factors such as<br />
to a decrease in HbA 1c by approximately 1–2%. [40] plasma lipids. Consequently, other potentially<br />
The effect is dependent upon the presence of some vasoprotective effects of metformin have been inendogenous<br />
β-cell function, and is largely indepen- voked. Reported benefits of metformin on non-clasdent<br />
of bodyweight, age and duration of diabetes. sic cardiovascular risk factors (table V) include in-<br />
However, given the progressive nature of type 2 creased fibrinolysis and a reduced concentration of<br />
diabetes, re-assessment of dosage and consideration the anti-thrombolytic factor plasminogen activator<br />
of additional therapy are required to maintain gly- inhibitor-1 (PAI-1). [41,46] The mechanism of the<br />
caemic control in the long term. [4,21] Metformin has cardioprotective effects of metformin remains unseveral<br />
features that mark it out as a good choice for certain. Detracting somewhat from this generally<br />
first-line monotherapy. The anti-hyperglycaemic ac- favourable view was evidence of an initially greater<br />
tion of metformin means that it is unlikely to cause mortality when metformin was added to a sulphonysevere<br />
hypoglycaemia. This may be explained in lurea in a UKPDS substudy, [47] but longer-term folpart<br />
because metformin does not stimulate insulin low-up has shown the benefits of metformin to be<br />
1 The use of trade names is for product identification purposes only and does not imply endorsement.<br />
© 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)