Tayside Diabetes MCN Handbook
Treatment with Oral Hypoglycaemic Agents

Aims of Drug Treatment

to alleviate hyperglycaemic symptoms, improve control of glucose, and reduce microvascular complications
to minimise hypoglycaemia and weight gain
where possible, to prevent long term complications of diabetes
to reduce or avoid aggravating cardiovascular risk (BP, cholesterol, events i.e. MI, stroke)

When to consider tablets

in type 2 diabetes with inadequate glycaemic control after 12 weeks diet and lifestyle advice
sooner if severe symptoms or adequate control unlikely to be achieved with non-pharmacological measures
metformin is not currently licensed in pregnancy but is likely soon to become the agent of choice before the end of 2008 in gestational diabetes (July 2008)

Tablets should be replaced by insulin in the presence of severe intercurrent illness, especially if ketosis is present.

Dosage Alteration

For any therapy, changes in dosage should usually be gradual i.e. intervals of 8-12 weeks

**Remember prescriptions are free for all patients who receive oral hypoglycaemic agents or insulin**

Drug Mechanisms, indications and recommendations

This is an exciting time for the treatment of type 2 diabetes, with the increasing availability of new therapies. However, this also makes it less clear how these drugs should be used and in what order of preference. Any recommendations are made on the basis of current evidence and considered opinion at the time of writing and will be reassessed when new evidence or guidance becomes available.

Algorithm for Use of Oral Hypoglycaemic Agents

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Metformin

Metformin is weight neutral, and in some studies was associated with weight loss. In the UKPDS, all cause and cardiovascular mortality was reduced in those achieving intensive control of glycaemia with metformin compared to patients receiving conventional management with other agents. It acts primarily to decrease liver glucose production but also it decreases gut glucose absorption and may increase peripheral glucose disposal.

Metformin should be considered as the drug of first choice in overweight or obese individuals with type 2 diabetes. There is no evidence that Metformin is ineffective in non-overweight individuals so it should be considered in this group, although sulphonylureas would be a reasonable alternative.
It can be used alone or if necessary with any other diabetes therapy. It carries a low risk of hypoglycaemia.
GI side effects are experienced in up to 25% of patients, although only 5% cannot tolerate it. Metformin should be started in low dose and built up gradually in 2 or 3 divided doses to a dose 1g bd or 850mg bd with or after food, to a usual maximum of 2g/day. Slow release preparations of Metformin have now been approved by SMC. There is some evidence to suggest that in those intolerant of standard formulations of Metformin, slow release formulations are better tolerated. A trial of Metformin MR (Glucophage SR) could therefore be considered in those patients with severe GI side effects who would otherwise discontinue immediate release Metformin. If no benefit in GI side effect is seen within 6 months, Metformin MR should be stopped and an alternative agent commenced.
Metformin is renally excreted and accumulation may precipitate lactic acidosis. The dose of Metformin should be reduced when the eGFR falls below 45mls/min. Metformin should be stopped when the eGFR falls below 30ml/min. For further information see Section on Screening and Management of Kidney Complications. Patients with deteriorating renal function should be monitored closely.
Hepatic impairment, severe infection, trauma, dehydration, and heavy alcohol use, are also contraindications to Metformin use.
Metformin is classically contraindicated in heart failure due to an increased risk of lactic acidosis and should be avoided where there is a suspected risk of tissue hypoxia. However, clinical trials are now in progress examining its effect in stable congestive heart failure patients and there is epidemiological evidence to suggest no adverse effects of metformin in stable heart failure.
Metformin should be stopped in patients admitted with severe infection or undergoing major surgery; in this situation, hyperglycaemia should be managed with insulin. For further information see Perioperative Guidelines.
Metformin should also be stopped prior to any procedures which involve use of iodinated contrast. For further information see Preparations Prior to ProceduresPreparations Prior to Procedures.