2,46 Mb - GuíaSalud

without heart failure. In this study, there were no favourable differences to pioglitazone
within the main variable, though they did arise in the compound variable
performed in the SR, so caution is required in the interpretation of these findings
(131).
These results are recorded in a safety specification in the Spanish Medicines
Agency (132).
The use of thiazolidinediones can result in an increase in fracture risk in
women. According to the analyses carried out by the manufacturer (130), the use
of pioglitazone presents a fracture excess of 0.8 cases/year for every 100 women
under treatment. This excess is similar to that observed for rosiglitazone in
the ADOPT study (133). Most of the fractures took place in the extremities. The
mechanism is still unknown.
These data have been recorded in the pharmacological warnings of the FDA
(134) and the Spanish Medicines Agency (135). Recently rosiglitazone has been
withdrawn from the market.
The incretin effect is the increase of insulin secretion stimulated by the increase
of glucose, through intestinal peptides. The incretin system consists of
two peptides, the GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent
insulinotropic polypeptide). The incretins are quickly inactivated by the DPP4
(dipeptidyl peptidase 4) enzyme. Analogue drugs to the GLP-1 (exenatide) receptors
have been developed recently. They interact with the GLP-1 receptor and
are resistant to be degraded by the DPP4 enzyme. These drugs require parenteral
administration. Exenatide and liraglutide can be administered once or twice a day,
subcutaneously and even only once a week (exenatide).
Another group of drugs includes the DPP4 inhibitors, which are administered
orally (sitagliptin, vildagliptin and others).
A recent SR (119) has analysed the 29 RCTs which compared the addition of
these new drugs in comparison to placebo, showing a 0.97% (CI 95%: 0.81-1.13)
reduction for HbA 1
c for the GLP-1 analogues and 0.74% (CI 95%: 0.62-0.85) for
the DPP4 inhibitors, so they are not inferior to other hypoglycaemic agents. The
GLP-1 analogues produce weight loss (1.4 kg and 4.8 kg in comparison to placebo
and insulin, respectively), while the DPP4 inhibitors have no effect on weight.
The GLP-1 analogues have gastrointestinal adverse effects (RR 2.9 for nauseas
and 3.2 for vomits). The DPP4 inhibitors have a higher infection risk (RR of 1.2
for nasopharyngitis and 1.5 for urinary infection) and headaches. Most RCTs last
30 weeks maximum, therefore long-term safety has not yet been assessed.
RCT
1+
Evidence summary
1++ Metformin, second generation sulfonylureas, repaglinide and thiazolidinediones c are
similar in effectiveness as regards HbA 1
c reduction (nateglinide and alpha-glucosidases
inhibitors seem to be less effective (111;112).
1+ In obese diabetics, the treatment with metformin, in comparison with conventional therapy
(sulfonylureas or insulin), reduces the risk of any event related with diabetes (113).
64 CLINICAL PRACTICE GUIDELINES IN THE NHS