Ricerc@Sapienza

Type 2 diabetes is a devastating disease causing several end-organ damages throughout the
body. Vascular complications are the major disease burden responsible for the increased
morbidity and mortality of diabetes. Therefore, the primary goal of diabetes treatment should
be to safely prevent, delay, or slow down the progression of complications.
While pharmaceutical companies race for commercializing new hypoglycaemic drugs, there are
only few and sparse data showing that using one drug instead of the other one effectively
impact vascular complications. At the end, several drugs for type 2 diabetes therapy are
available but whether these drugs really match the primary goal of treatment, especially in
primary prevention, is uncertain. That is despite the results of cardiovascular outcome trials
published since 2013. In terms of macrovascular complications, only about 35% of the
currently commercialized drugs approved for diabetes treatment have cardiovascular data
from ad hoc randomized controlled trials and most of these trials were not powered to
explore cardiovascular efficacy, but only safety.
2 What about the remaining 65%? In terms of
evidence-based medicine, we are prescribing the majority of anti-diabetes drugs (and
spending money) just to lower HbA1c, with a possible indirect effect on complications which
has not really been proven beneficial. When we move to microvascular complications, the
situation is even worse. Our knowledge about the impact of diabetes prescriptions on
microvasculature is stuck at the evidences from trials evaluating intensive glycaemic control.
All we have is information from subgroup or post-hoc analysis from some (even not all)
cardiovascular outcome trials. In the best cases, microvascular outcomes, especially renal
outcomes, have been considered as pre-specified secondary outcomes of the trials.
We have no data from large randomized controlled trials specifically designed to show whether
we may avoid blindness or neuropathy by using a specific anti-diabetes drug.
In 2008 the Food and Drug Administration (FDA) issued a “Guidance for industry” calling
for long-term safety trials evaluating cardiovascular risk of new antidiabetic therapies.