Abc do diabetes

Abc do diabetes

(Parte 8 de 19)

Time from randomisation (years)

Medlah HbA (%)

Patients followed for 10 years Conventional

Intensive

All patients assigned to regimen

Conventional Intensive

Cross sectional and 10-year cohort data for HbA1cin patients receiving intensive or conventional treatment, from UKPDS (Type 2 diabetes; see page 42)

Approaches to management

There are three distinctive aspects in management, each of which requires entirely different approaches

•To alleviate symptoms and improve quality of life, achieved by reducing hyperglycaemia and weight

•To maintain health by reduction of risk factors (especially hypertension, hyperlipidaemia, and smoking) and by screening programmes to diminish the development of diabetic complications •Management of diabetic complications

•Management of other medical problems

Treatment of Type 2 diabetes mellitus metformin is the first choice, and will to a small extent diminish the weight gain which comes almost inevitably with improved glycaemic control. A sulphonylurea or meglitidine analogue is added when metformin alone fails. The use of thiazolidinediones is described below.

Patients who remain unwell and often symptomatic (thirst and nocturia especially) and who continue to lose weight should be switched to insulin without delay.

Achieving glycaemic control and reducing risk factors •Healthy lifestyle advice—healthy eating plan, exercise, and weight reduction plan.

•Oral hypoglycaemic agents should be given only when dietary treatment alone has failed after a proper trial period, usually lasting at least three months. They should not normally be given as the initial treatment (this is a common error).

• Sulphonylureas stimulate insulin secretion •Meglitidine analogues stimulate insulin secretion

•Biguanides (metformin)reduce hepatic gluconeogenesis and enhance glucose uptake • Thiazolidinediones enhance insulin sensitivity

• glucosidase inhibitors (acarbose)reduce absorption of complex carbohydrates. •Pharmacological agents to assist weight reduction:

•Orlistatinhibits pancreatic lipase and reduces fat absorption

•Sibutramineis a monoamine reuptake inhibitor, causing reduced appetite

•Antihypertensive and lipid lowering agents (see chapter 17).

Sulphonylureas Seven sulphonylureas are available. They are remarkably safe and free from side effects, although rare toxic effects have been reported, including rashes and jaundice. Only one sulphonylurea should be used at a time since there is nothing to be gained from any combination of these drugs and there is no evidence that any one drug is likely to be more successful than another.

Selecting a sulphonylurea is largely a matter of personal choice, though it is now usual to use one of the shorter acting, metabolised drugs such as gliclazide or glipizide, which are suitable for all ages and for those with renal impairment as well. Glibenclamide, which has the advantage of once-daily use, is still suitable for younger patients, but is contraindicated in the elderly. Glimepiride is also given once daily and may cause less hypoglycaemia. Excessive doses can cause hazardous (even fatal) hypoglycaemia, and it is thus usual to start treatment with the smallest useful dose. If hypoglycaemia does occur in a patient taking a sulphonylurea, the drug should be stopped or at the very least the dose substantially reduced.

Chlorpropamide is now obsolete. It has a very long half life, thus increasing the risk of hypoglycaemia, and many patients experience an unpleasant facial flush on drinking very small amounts of alcohol.

Meglitidine analogues The mode of action of this group of drugs is similar to that of sulphonylureas though acting at a different site. Their advantages are the rapid onset and short half life, efficacy when taken just 15 minutes before meals, and a duration of effect of no more than three hours. They are omitted if no meal is taken. There may be some benefit in reducing postprandial glycaemia and in theory at least there might be less hypoglycaemia.

Daily dose ranges for oral hypoglycaemic agents

Oral hypoglycaemic agentsDose range (mg)

Sulphonylureas

Meglitidine analogues*

Nateglinide 180-540 Repaglinide 1·5-16

Biguanide Metformin 1000-2000

Thiazolidinediones glucosidase inhibitors Acarbose 50-600

*Meglitidine analogues are taken three times daily; before meals. Most of the other drugs can be started as single daily doses, but as requirements increase are more effective in divided doses

Percentage of doses taken during observation period

Twice dailyOnce daily3 times daily 0

Increased patient compliance is associated with once-daily oral hypoglycaemic agents

The hypoglycaemic effect of early sulphonamides was observed in the 1940s, and in the next decade first tolbutamide (1956) and then chlorpropamide (1957) were introduced into clinical practice. They act chiefly by stimulating insulin release from the B-cells of pancreatic islets

ABC of Diabetes

Use of metformin

•Drug of first choice for overweight Type 2 diabetes •May reduce mortality (UKPDS)

•Never use when creatinine is 150 mol/l

•Danger of lactic acidosis if given to: renal failure patients patients with liver disease patients with a high alcohol intake •Not to be used for thin patients or those in heart failure

•During intravenous contrast procedures: stop metformin for 48 hours beforehand and do not restart until 48 hours after procedure completed

Nateglinide is one of a new class of oral hypoglycaemic agents, namely an amino acid derivative. Insulin release after meals is both faster and of shorter duration than that with either sulphonylureas or repaglinide, giving less postprandial hyper-insulinaemia and less reactive hypoglycaemia. It is licensed only for use in combination with metformin, but not for monotherapy or substitution for conventional sulphonylureas.

Biguanides: metformin Biguanides act chiefly by reducing hepatic glucose production. They also enhance peripheral glucose uptake, and to some extent reduce carbohydrate absorption. Metformin is the only biguanide available in the United Kingdom. It is the drug of choice in the treatment of overweight Type 2 diabetic patients when diet alone has failed. UKPDS found some evidence for a reduction in mortality after the use of metformin.

Lactic acidosis is a serious consequence of the inappropriate use of metformin. It is contraindicated in any patient with renal failure, and serum creatinine should be monitored. A creatinine concentration above 150 mol/l indicates that the drug should be stopped. Metformin should not be used in any seriously ill or shocked patient, nor in those with heart failure, serious liver disease or a very high alcohol intake. It is not appropriate for the treatment of thin diabetic patients nor for use in frail elderly patients.

Glucosidase inhibitors

These agents block the enzyme responsible for the breakdown of complex carbohydrates in the gut and can effectively reduce the increase in blood glucose after a meal. Acarbose acts in this way and can be used alone or in combination with other oral hypoglycaemic agents. Its hypoglycaemic effect is relatively small and the severe flatulence which develops (to some extent avoidable by starting with small amounts) deters many patients from using it.

Thiazolidinediones This newly introduced group of hypoglycaemic agents act by reducing insulin resistance and by activation of the peroxisome proliferator activated receptor expressed predominantly in adipose tissue.

(Parte 8 de 19)

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