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8.2. Insulin therapy
8.2.1. Association of insulin with oral antidiabetic drugs
A Cochrane (144) SR and several subsequent clinical trials (145-147) have assessed
the effect of the combination of insulin with oral anti-diabetic drugs in
contrast to monotherapy with insulin. All the trials assess glycemic control and
the adverse effects, though they do not assess the effect on morbimortality. The
guidelines and types of insulin used differ in diverse trials. In the SR (144), the
combination of NPH (Neutral Protamine Hagedorn) insulin on a single night dose
associated with an oral anti-diabetic drug presented a glycemic control comparable
to monotherapy with human insulin (no analogues) every 12 hours or on
a multiple schedule. Weight increase was much less with the night schedules of
insulin associated with metformin (with or without sulfonylureas) in contrast to
monotherapy with insulin (144).
The results of the subsequent studies follow the same lines; in general, the
association of metformin with insulin improves glycemic control (expressed in
HbA 1
c reduction) (146-148), with less weight gained (145-147). The results in relation
to the frequency of hypoglycaemias vary among the different studies; in the
SR (144) no differences were observed as regards hypoglycaemia events, though
in other studies (145; 148) the treatment combined with a dose of insulin plus
metformin was associated with less hypoglycaemias in comparison with insulin
taken twice on a daily basis.
In the Douek (146) study more hypoglycaemias were observed than in the
group with insulin plus metformin in comparison to insulin with placebo.
In general, the more intense the treatment is, the better the achievement of
glycemic control and the higher the incidence of hypoglycaemia. Should there be
no conclusive evidence on which guideline is better, then the patient’s preferences
(79) and the risk of adverse effects, mainly hypoglycaemia, should be taken into
consideration.
SR of RCT
and RCT
1+
8.2.2. Insulin analogues
There are many possible insulinization schedules, both as regards dosage frequency
as the type of insulin: fast-acting insulin, intermediate or mixed human insulin
or fast-acting analogues of human insulin (lispro, aspart and glulisine) or slowacting
insulin analogues (glargine and detemir).
Fast-acting insulin analogues are absorbed faster and manage to double the
concentrations of insulin in plasma in half the time in comparison to human insulin,
due to their pharmacokinetics. This characteristic creates lower glucose levels
after the meals. Another advantage of fast-acting insulin analogues would be the
possibility to inject insulin just before the meals.
While fast-acting insulin analogues are used to imitate the response of eNdogenous
insulin to the intake or to improve or prevent «inter-intake» hyper-
70 CLINICAL PRACTICE GUIDELINES IN THE NHS