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Definitive proof for CV protection afforded by T2DM treatment is scant
to say the least, so much so that the spectre of increased CV risk due to
T2DM treatment looms large in the minds of many experts.
The results from these trials may relate to the particular drugs used rath-
er than difference between intensive and conventional management.
There have been many high profile cases concerning the use of some
compounds and an associated increase in CV events with the most
infamous being rosiglitazone and to a lesser extent the first generation
SU, tolbutamide. 49, 50 Naturally, these fears have placed the TZDs, as a
class, under great scrutiny, but the fact remains that large trials and
meta-analyses (i.e. PROactive, Nissen and Wolski’s meta-analyses and
RECORD) do not provide definitive answers with regard to the CV safety
of these compounds. 42, 46, 50, 51

Prompted by these concerns, the FDA conducted a systematic review
of epidemiologic studies of CV risk in patients treated with rosiglitazone
or pioglitazone, the results of which are consistent with results of the
52
same organisation’s meta-analyses of randomised clinical trials with
these two TZDs. The salient point from these analyses is that it is highly
53
likely that rosiglitazone therapy is associated with increased risk of ad-
verse CV outcomes. 53

Ongoing studies

There are a number of ongoing trials investigating the CV outcomes
associated with T2DM treatment. The driving force behind the relatively
recent initiation of these large trials, often involving more than 10,000
patients, is the fact the regulatory bodies now require CV safety on all
new and emerging T2DM treatments. These CV outcome trials are sum-
marised in Table 2.

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