Oral Antidiabetic Agents - Luzimar Teixeira
Oral Antidiabetic Agents - Luzimar Teixeira 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)
Oral Antidiabetic Agents 409 On theoretical grounds, the thiazolidinediones appear promising, particularly with respect to poss- ible preservation of β-cell function and the potential for cardiovascular disease prevention. However, these agents have perhaps not entirely fulfilled early expectations of success, at least if judged in terms of their glucose-lowering abilities, which are no better than the conventional drugs. Part of this shortfall may be attributable to the complexity and hetero- Table VIII. Relative costs and frequency of prescriptions for oral antidiabetic drugs in the UK [71,72]a Drug Frequency of prescriptions Relatively inexpensive Biguanides Only metformin b in UK Sulphonylureas c Moderate α-Glucosidase inhibitors Sulphonylureas c Only acarbose in UK Relatively expensive Rapid-acting prandial insulin Repaglinide, nateglinide releasers Thiazolidinediones Rosiglitazone, pioglitazone a This classification attempts to take average effective maintenance dosages into account and may be regarded as an approximate guide to relative UK Drug Tariff prices. b Use of metformin has increased in recent years, this drug now being the most widely prescribed oral antidiabetic agent in the UK (49%); sulphonylureas lie close behind, gliclazide being the most popular agent accounting for 31% of spending on oral antidiabetic agents. Thiazolidinediones account for only 5% of all prescriptions but for 32% of the cost of all oral antidiabetic agents in the UK; these figures predate the 2003 license amendment permitting limited prescription of thiazolidinediones as monotherapy in selected patients. Acarbose, the only α-glucosidase inhibitor in the UK, and the rapid-acting prandial insulin releasers repaglinide and nateglinide account for a small percentage (
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<strong>Oral</strong> <strong>Antidiabetic</strong> <strong>Agents</strong> 409<br />
On theoretical grounds, the thiazolidinediones<br />
appear promising, particularly with respect to poss-<br />
ible preservation of β-cell function and the potential<br />
for cardiovascular disease prevention. However,<br />
these agents have perhaps not entirely fulfilled early<br />
expectations of success, at least if judged in terms of<br />
their glucose-lowering abilities, which are no better<br />
than the conventional drugs. Part of this shortfall<br />
may be attributable to the complexity and hetero-<br />
Table VIII. Relative costs and frequency of prescriptions for oral<br />
antidiabetic drugs in the UK [71,72]a<br />
Drug<br />
Frequency of prescriptions<br />
Relatively inexpensive<br />
Biguanides<br />
Only metformin b in UK<br />
Sulphonylureas c<br />
Moderate<br />
α-Glucosidase inhibitors<br />
Sulphonylureas c<br />
Only acarbose in UK<br />
Relatively expensive<br />
Rapid-acting prandial insulin Repaglinide, nateglinide<br />
releasers<br />
Thiazolidinediones<br />
Rosiglitazone, pioglitazone<br />
a This classification attempts to take average effective<br />
maintenance dosages into account and may be regarded as<br />
an approximate guide to relative UK Drug Tariff prices.<br />
b Use of metformin has increased in recent years, this drug<br />
now being the most widely prescribed oral antidiabetic agent<br />
in the UK (49%); sulphonylureas lie close behind, gliclazide<br />
being the most popular agent accounting for 31% of spending<br />
on oral antidiabetic agents. Thiazolidinediones account for<br />
only 5% of all prescriptions but for 32% of the cost of all oral<br />
antidiabetic agents in the UK; these figures predate the 2003<br />
license amendment permitting limited prescription of<br />
thiazolidinediones as monotherapy in selected patients.<br />
Acarbose, the only α-glucosidase inhibitor in the UK, and the<br />
rapid-acting prandial insulin releasers repaglinide and<br />
nateglinide account for a small percentage (
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