Page 90 - 51 the significance--29.2_opt

Should the results of the above trials be overwhelmingly positive, they
will prove that T2DM treatments can provide benefits beyond simply
lowering blood glucose levels. The data will provide an insight into the
cardiovascular safety and potential cardiovascular protection of the
compounds being investigated. The results of these trials in conjunction
with an increased knowledge of disease genetics and drug mode of
actions could stimulate a reappraisal of T2DM management.

Emerging therapeutic classes

DPP-4 inhibitors

DPP-4 inhibitors are oral anti-diabetics. They do not require an up-
titration period, are weight neutral and are associated with significant
improvements in glucose control in patients with T2DM by preventing the
inactivation of the incretin hormone GLP-1, which stimulates glucose-
dependent insulin secretion and suppresses glucagon secretion.
16

DPP-4 inhibitors are efficacious over a broad range of HbA levels.
1c
They have shown to be effective as both monotherapy and as add-on
therapy to metformin, SUs, TZDs and insulin in subjects who lack ad-
equate glycaemic control. In addition to their demonstrated efficacy
16
as mono- and add-on therapy they are also generally safe and have a
placebo-like tolerability profile.
16
Long-term safety data for DPP-4 inhibitors is still lacking, although they
are now included in the most recent US and European guidelines 2, 62
There are concerns regarding the ubiquitous tissue expression (liver,
lung, lymphocytes, etc) of the DPP enzymes, their role in tumour sup-
pression and their interaction with other hormones besides GLP-1. 63-67 To
date there is nothing in the safety record of DPP-4 inhibitors to suggest
these concerns have any clinical grounding Also, due to the way that
sitagliptin, vildagliptin and saxagliptin are cleared from the body, their
use is not recommended in patients with moderate to severe renal in-
sufficiency and because they have not been studied in severe hepatic
insufficiency their use is also not recommended in the these patients
(vildagliptin should not be used in any type of hepatic impairment). 68-70
Linagliptin on the other hand can be used without dose adjustment in
all stages of renal impairment. Table 3 presents a ‘SWOT’ analysis of the
DPP-4 inhibitors.

90