Bjpcn-cardiovascular.com

TherapeuticsReview
Optimising treatment of type 2 diabetes with metformin
There is good evidence that tight glycaemic control significantly improves
outcomes in patients with type 2 diabetes. All practice nurses will be
looking to achieve the new General Medical Services contract (GMS2)
targets for HbA
reduction in diabetes (see box). Practices will be
developing prescribing strategies to achieve this reduction, in accordance
with good clinical practice. Metformin offers an important first-line
therapy for type 2 diabetes. The introduction of a new, sustained-release
Dr Mike Mead
formulation – Glucophage SR – should improve patient compliance with
General Practitioner, Forest House
Medical Centre, Leicester
metformin and so improve glycaemic control.
Starting therapy with metformin
26% lower risk of a diabetes-related end
renal impairment. Check a patient’s renal
When initiating therapy for patients with
point. Metformin was also associated with
function before starting metformin and
type 2 diabetes, the first drug to consider
a 29% lower risk of all-cause mortality
don’t use the drug if their creatinine is
is metformin – for four good reasons:
compared with sulphonylureas or insulin.
No significant effect on diabetes-related
HbA targets in GMS2
1. Metformin increases insulin sensitivity
mortality was found with sulphonylureas
and targeting insulin resistance reduces
or insulin. Cardiovascular disease
cardiovascular risk in patients with type 2
accounted for 62% of deaths in the dietary
diabetes. Insulin resistance encompasses
arm of this trial and compared with diet,
dyslipidaemia (raised triglycerides, low
metformin gave a 39% reduction in
HDL–cholesterol, raised small dense
myocardial infarction. Metformin has,
LDL–cholesterol) and hypertension, as well
therefore, clearly proven benefits in
as the hyperglycaemic component of
reducing mortality and cardiovascular
type 2 diabetes.
disease in patients with type 2 diabetes.
>130 mmol/L. Metformin needs to be
2. The United Kingdom Prospective
3. NICE guidance has recommended that
stopped 48 hours before use of iodine-
Diabetes Study (UKPDS) showed that
metformin should be used as the first-line
containing X-ray contrast media and
metformin was at least as effective as
glucose-lowering therapy in patients
48 hours before surgery requiring general
sulphonylureas or insulin in controlling
whose blood glucose is inadequately
anaesthesia.
blood glucose and was associated with a
controlled with lifestyle intervention. More
precisely, it recommended
Potential problems with standard
metformin for those with a BMI
metformin therapy
>25 kg/m2 with a ‘consideration’
There are two main problems with
for patients who are not
standard metformin therapy. First, the
overweight – this is conservative
dosing schedule, which requires a twice-
as metformin works as well in
daily or three times daily regimen,
patients with normal weight and
potentially making good compliance
is a perfectly valid option in such
difficult for patients. Second, the side-
patients.
effects that can occur with metformin. The
main side-effects that may limit
4. Compared with sulphonylureas,
compliance are gastrointestinal, including
metformin has less potential for
diarrhoea, vomiting, nausea, anorexia,
weight gain and has a much lower
abdominal pain and a metallic taste.
risk of hypoglycaemia.
This message is getting through,
Non-adherence to metformin therapy is a
as currently nearly three-quarters
serious problem in practice and one that
of all newly diagnosed patients
we need to address in order to achieve
with type 2 diabetes receive
good glycaemic control and reach our
metformin as first-line therapy.
targets. One trial – the DART study – found
adequate adherence in only one-third
Precautions when starting
(34%) of patients prescribed metformin.
metformin
Incidence of myocardial infarction (heart attack) and microvascular There are well-known
Introduction of Glucophage SR
complications (eg eye problems) by updated mean haemoglobin A1c contraindications before starting
A new sustained-release formulation of
concentration, for white men aged 50–54 years at diagnosis and with meanduration of diabetes of 10 years. UKPDS Group.
metformin, including severe heart
metformin – Glucophage SR – is given
failure, hepatic impairment and
once-daily in the evening, with food to
delay gastric emptying. Previous research
has shown that a once-daily regimen of an
extended-release oral hypoglycaemic can
Optimising glycaemic
give better compliance (and glycaemic
control with metformin
information
control) than a twice-daily immediate-
release version of the same drug.
Glucophage SR has comparable efficacy in
lowering HbA
to standard metformin and
is as effective as metformin twice or three
times daily. Apart from the convenience of
34). Lancet 1998; 352: 854–865.
a once-daily dose, Glucophage SR has a
much lower incidence of gastrointestinal
NICE Inherited Clinical Guideline G.
side-effects (including 50% lower incidence
of diarrhoea) than standard metformin,
potentially encouraging compliance with
the drug and allowing us to titrate to a
higher dose without the patient
discontinuing their therapy. This means
that patients who are inadequately
controlled due to poor tolerability of
metformin (including those only managing
to take the lower doses) can be switched
diabetes: a retrospective cohort study.
to the new modified-release preparation to
Diabetic Medicine 2002; 19: 279–284.
restore and improve their HbA
control.
Conclusion
Metformin is now central to the therapy of
patients with type 2 diabetes and every
effort should be made to improve
compliance with the drug, particularly if
release formulation. Clin Ther 2003; we are to reach the targets for HbA
25: 515–529.
new GMS contract.

Source: http://www.bjpcn-cardiovascular.com/pdf/2006/Vol1_Num2_July_2004_p80-81.pdf?sid=57f6fb74336d5cc3