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5. The future of anti-diabetics in T2DM
therapy

Professor Ele Ferrannini Dr Thomas Hach
Department of Internal Medicine TA Metabolism
University of Pisa School of Medicine Boehringer Ingelheim Pharma GmbH & Co. KG
Pisa, Italy Ingelheim, Germany

Unmet needs in T2DM therapy

As we have seen in Chapter 1, T2DM is a huge, global problem. Many
treatments are available to tackle this chronic and potentially serious
condition, but the fact is that, in many patients, long-term glycaemic
control and adherence to therapies is far from optimal; limited by a
lack of sustained efficacy, safety and tolerability issues and product
label restrictions. These problems are compounded in those patients
with comorbidities that interfere with diabetes therapy, such as renal
impairment.

Beyond HbA in assessing treatment efficacy
1c
Assessing the degree to which glycaemic control is achieved hinges on
a number of parameters. If these targets are not met then glycaemia is
considered to be uncontrolled. These targets are as follows:

z HbA : <7.0% 1
1c
2
z FPG: 3.9 – 7.2 mmol/L (70 – 130 mg/dl)
3, 4
z 2-hour postprandial blood glucose: <7.8 mmol/L (<140 mg/dl) up to <10
mmol/L (<180 mg/dl) 5

As these targets indicate whether glycaemia is controlled or not, they
relate directly to the efficacy of any given therapy in lowering blood
glucose levels in patients with T2DM. For this reason, the level of effic-
acy of any treatment will remain an important decision factor in choos-
ing the most appropriate agent.
HbA , as a proxy for efficacy, is the current gold standard in monitoring
1c
treatment and informing management decisions in people with diabe-
tes. However, using this measure in isolation is not without its limitations.
6
6
HbA reflects the mean blood glucose level during the preceding six
1c
to eight weeks, but this is true only for the population as a whole, not
the individual patient. For assessing the efficacy of a given treatment
6
in the future we should take a more holistic approach. It is known that
about 33% of people diagnosed as having T2DM based on postprandial
(PPG) hyperglycaemia have normal fasting plasma glucose (FPG). It
7
has been shown that the deleterious effects of dysglycaemia – daily
excursions in FPG and PPG – develop before diabetes is diagnosed.
8
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