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The optimum dose in most patients is around 2,000 mg/day (116).
Metformin’s most common adverse effects are gastrointestinal (abdominal
pain, nausea and diarrhoea) which can appear in 2% to 63% of cases in comparison
to the 0% to 32% with second generation sulfonylureas and 0% to 36% with
thiazolidinediones (111). These symptoms can be reduced by consuming food and
the slow dose titration. In less than 5% of patients, it is necessary to withdraw the
drug (117).
Lactic acidosis is another important and severe adverse effect which has
been recently assessed in an SR (118), and which has not objectified an excess
of cases in the group treated with metformin. The incidence of lactic acidosis in
the group treated with metformin was 6.3 cases for every 100,000 patients/year in
comparison to 7.8 cases in the group without it.
Nevertheless, the SR includes an insufficient number of patients with renal
or hepatic failure, which makes it difficult to assess the risk in these groups.
According to the technical specifications, the use of metformin is contraindicated
for patients with serum creatinine over 1.5 mg/dl for men and 1.4 mg/dl for women.
The safety of metformin has nor been analysed in patients with severe renal
failure, with creatinine clearance below 30 ml/min.
The insulinsecretagogues (sulfonylureas and metiglinides) work by stimulating
the release of insulin through beta cells from the pancreas, so a certain insulin
reserve is required. They are effective to reduce HbA 1
c.
The sulfonylureas proved effective to reduce morbidity related to diabetes
and in microangiopathy (106), while metiglinides have no studies on morbimortality
(119).
Sulfonylureas should be considered first line alternative treatment when metformin
is not tolerated or it is contraindicated, or for people who are not overweight.
Sulfonylureas and glinides provoke weight increase as well as an increase
in the risk of hypoglycaemia.
A sulfonylurea should be chosen as a first option as, although they are not
better than the new oral antidiabetic drugs as regards glycemic control, there is a
wider usage experience and they have proved to be effective and much cheaper in
long-term RCTs (111).
Gliclazide and glimepiride could be useful for elderly patients or when there
is mild-moderate renal failure due to less severe hypoglycaemias risk (120); moreover,
sulfonylureas on a single daily dose (gliclazide and glimepiride) can be useful
when there is suspicion of therapeutic compliance problems (79; 120).
Metiglinides (repaglinide and nateglinide) have a quick action onset and
short-term activity; it is recommended to be taken before each main meal.
These drugs can play a role in glycaemia control in patients with non-routine
daily models (patients with irregular meals or who omit some meals) (79).
RCT
1+
SR of RCT
1+
RCT
1+
SR of RCT
1+
CPG, Expert
opinion
4
Expert
opinion
4
62 CLINICAL PRACTICE GUIDELINES IN THE NHS