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“Failure-based” treatment strategies

Several large, randomised trials have demonstrated that intensive
treatment can improve outcomes in people with T2DM. For example,
post-trial monitoring data from the UKPDS shows that patients who re-
ceived intensive treatment during the study continue to have a signifi-
cantly decreased risk of any diabetes-related endpoint over the long
term; an effect that is known as “a legacy of improved outcomes” be-
cause early intensive treatment leaves a legacy of clinical benefits. 29, 30
Controlling glycaemia more aggressively, instead of simply waiting for
treatment failure aims to avoid the phenomenon known as ”metabolic
memory”. This concept, which refers to diabetic vascular stresses per-
sisting after glucose normalisation, has been supported by laboratory
and clinical data. 31, 32

The progressive nature of T2DM requires regular monitoring and adjust-
ment of treatment, but all too often management strategies for this
condition are ‘failure based’, in that there is a tendency to persist with
monotherapy until blood glucose levels are no longer controlled.
23
There appears to be inertia in primary care impeding the adoption of
an aggressive, treat-to-target approach (i.e. early enforced normali-
zation of blood glucose levels) even though the benefits of intensive
management in the short- and long-term have been demonstrated by
some long-term studies.
An early switch to antidiabetic combination treatment that addresses
the dual endocrine defects of insulin resistance and β-cell dysfunction,
would deliver a markedly greater reduction in HbA for those patients
1c
who are struggling to meet their glycaemic targets. 33

Predictability of treatment response and the need for
individualised treatment

Currently, T2DM management is very much a ‘one treatment fits all’
affair. People with T2DM are generally treated in the same way re-
34
gardless of underlying differences that may affect their therapeutic re-
sponse. There is a huge variation in response, which makes it almost
34
impossible to predict the treatment effect in any given patient. Differ-
34
ences in genotype interact with external environmental factors to pro-
duce an in-vivo milieu that varies from person to person thus impacting
the effects of a medication. 34

Analyses have shown that in the USA only 56% of patients diagnosed
and treated for diabetes reach their glycaemic targets, whereas in
Germany the figure is 48% (glycaemic target for both the USA and
Germany is <7% HbA ). 35, 36 This failure in treatment leaves a substantial
1c

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