CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
358
AFRICA
and suggest no cardiovascular benefits
from early insulin initiation in high-risk
patients with early diabetes. This strategy
can therefore also not be recommended
for cardiovascular protection, but should
be used on merit for diabetes control.
However, it is important to note is that
the early use of insulin glargine targeting
normoglycaemia of
<
5.3 mmol/l
had no adverse effect with regard to
cardiovascular outcomes.
There were however two positive
outcomes/conclusions from this part of
the trial. The first was the safety of
glargine insulin, which this study has now
proven beyond any doubt to be a safe
insulin. Glargine now has more safety
data than most other medicines and much
more than any other insulin (10 years),
with no sign at all to suggest increase in
cancer risk. The risk of hypoglycaemia in
the study was also fairly low and weight
gain was only 1.6 kg over the 6.2 years of
average follow up.
The second positive outcome was that
the glargine group slowed progression
from dysglycaemia to diabetes in the
subgroup with IGT and IFG (
n
=
1 456),
with a 28% risk reduction despite a 1.6-kg
weight gain. The question remains if this
would be a cost-effective intervention
to consider in these patients, and further
study will be required.
As in the UKPDS study, an 8.5-year
extension of follow up proved to be
invaluable with regard to microvascular
outcomes. In that light, a further two years
of follow up has already been announced,
which might generate further interesting
data. Currently, I don’t think this strategy
can be used in general practice as routine
management.
Dr Larry Distiller, Centre for
Diabetes Education, Houghton,
Johannesburg
It is probably not surprising that there
was no demonstrable reduction in
cardiovascular outcomes in patients on
glargine insulin compared to the standard-
care group. Firstly, although these were
ostensibly ‘new-onset’ diabetes patients,
all were at high risk, with documented
cardiovascular disease at the time of
selection, and, as with the ADVANCE,
ACCORD and VADT trials, one would
not expect a reversal of cardiovascular
event rates in just seven years in patients
with documented vascular disease.
Secondly, the difference in HbA
1c
levels achieved between the standard-care
and glargine group was just 0.3%, with
both groups achieving mean HbA
1c
levels
≤
6.5%. Unless one was to anticipate
a specific protective effect of insulin
itself, one would not anticipate a different
outcome between the two groups based
on differences in glycaemic control alone.
The positive aspects of this study are
that tight glycaemic targets are achievable
without increasing cardiovascular
mortality, even in high-risk patients, and
that glargine insulin can be used safely as
a therapeutic option in both high-risk and
recently diagnosed diabetes. The weight
gain documented and the amount of
hypoglycaemia experienced is acceptable
and not excessive.
It is unlikely that the outcomes reported
in this trial will have any significant
impact on the current approaches to the
management of diabetes in the clinical
setting.
Dr Landi Lombard, Dr Larry Distiller,
Julia Aalbers
1.
The ORIGIN trial investigators. Basal insu-
lin and CV and other outcomes in dysglyce-
mia.
N Eng J Med
. Epub 11/6/2012. DOI:
10.1056/NEJMoa1203858.
Advertorial
Lantus
®
: our commitment to safety
Introduction
As an ethical pharmaceutical company with
a long-standing commitment to diabetes, the
safety and wellbeing of people with diabetes
is of paramount importance to Sanofi. Lantus
®
[insulin glargine (rDNA) injection] is already
supported by a wealth of available data1 result-
ing from more than 80 000 patients enrolled in
clinical trials and over 47 million patient-years
2
of treatment exposure to insulin glargine, which
showed no increased cancer risk with Lantus
®
.
1
Nevertheless, the company is committed to
contributing to the generation of knowledge
on the safety of insulin, including insulin
glargine. Further to the debate on the potential
relationship between insulin and cancer since
2009, and the safety of insulin glargine in this
context, we are taking an active stance to provide
accurate andmeaningful scientific information.
To this effect, Sanofi is working closely
with prominent scientists, health authorities
(EU, US and others), scientific associations
(including the American Diabetes Association)
and the American Cancer Society.
At theAmerican Diabetes Association 72nd
scientific sessions, we released new results of
a large-scale epidemiological programme to
evaluate cancer risk in diabetes and generate
comprehensive insulin glargine exposure data
from large databases.
Sponsored by Sanofi and conducted by
independent researchers in the northern
European countries, at Kaiser Permanente
in northern and southern California, and
at the University of North Carolina in the
United States, it is the largest observational
programme designed for this purpose to date.
Lantus
®
and cancer risk allegations
The role of (any) insulin and its potential
relation to cancer has been a matter of scientific
debate, where some studies published since
2009 have shown an association and others
have not.
In June 2009,
Diabetologia
published
four papers suggesting a possible relationship
between insulin analogs, such as insulin
glargine, and an increased risk of cancer. The
publications generated debate and concern
over the safety of such insulin treatments.
Limitations of the
Diabetologia
papers
In January 2011, the US Food and Drug
Administration (FDA) announced that it had
reviewed the four published papers and deter-
mined that the evidence presented was incon-
clusive.
3
Methodological limitations included:
•
Insufficient information on patients’ prior
and subsequent use of insulin products
•
Inadequate control of confounding risk
