Glucophage SR can now be used alongside lifestyle measures to reduce the risk or delay the onset of overt type II diabetes in overweight people with non-diabetic hyperglycaemia (impaired glucose tolerance, impaired fasting glucose or increased HbA1c) who are at high risk of progression to diabetes.
NICE defines impaired glucose tolerance as a fasting plasma glucose less than 7.0mmol/L and a 2-hour venous plasma glucose (after ingestion of 75g oral glucose load) of 7.8–11.1mmol/L. Impaired fasting glucose is a level of 6.1–6.9mmol/L and HbA1c is considered increased at a level of 42–47mmol/mol (6.0–6.4%).
Glucophage SR can be used when intensive lifestyle changes for 3 to 6 months have failed to stop progression to type II diabetes. Lifestyle modifications should be continued when metformin is initiated, unless the patient is unable to do so because of medical reasons.
Treatment with Glucophage SR must be based on a risk score incorporating measures of glycaemic control and including evidence of high cardiovascular risk.
Recommended by NICE
NICE public health guidance recommends standard-release metformin as an option to support lifestyle change for people at high risk of type II diabetes whose HbA1c or fasting plasma glucose has deteriorated despite participation in an intensive lifestyle-change programme or who are unable to participate in such a programme.
If the person is intolerant of standard-release metformin, NICE says that a modified-release preparation can be considered. The drug should be prescribed for 6–12 months initially and stopped if there is no effect on fasting plasma glucose or HbA1c levels at 3 months.
As when used to treat diabetes, dosing of Glucophage SR for diabetes prevention should be initiated with one 500mg tablet once daily with the evening meal. After 10 to 15 days, the dose should be adjusted on the basis of blood glucose measurements. A slow increase in dose may improve gastrointestinal tolerability. The maximum recommended dose is 4 tablets (2g) once daily with the evening meal.
Glycaemic status and risk factors should be regularly assessed to evaluate whether treatment needs to be continued, modified or discontinued.
In the 2.8 years of the Diabetes Prevention Program (DPP) (n=3234), patients treated with metformin were 31% (95% CI 17–43%) less likely to develop type II diabetes than those receiving placebo, compared with a risk reduction of 58% (95% CI 48–66%) for lifestyle modification versus placebo. DPP participants who were followed for a mean of 15 years in the DPP Outcomes Study (n=2776) showed a reduction in diabetes incidence of 18% (p=0.001) with metformin treatment and 27% (p<0.0001) with lifestyle intervention, compared with placebo.
As these results show, lifestyle modification is still the primary way of reliably reducing blood glucose levels. However, metformin represents a second intervention for instances where lifestyle modification is insufficient.
Metformin has been used in patients since 1957. Gastrointestinal disorders, such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite, are the most common adverse reactions. These generally occur during initiation of therapy and resolve spontaneously in most cases.
Glucophage SR is available as 500mg, 750mg and 1g sustained-release tablets.