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139
no benefit. The absence of benefit was found
in both primary and secondary outcomes
and also in all the subgroup analyses. This is
obviously very disappointing, with only a very
small reduction shown in triglyceride levels.
There is no positive take-home message here
and I cannot recommend the use of omega-3
fatty acids in this study population.
The second arm of the study assessed
insulin glargine versus standard care for
IFG, IGT or early diabetes in high-risk
cardiovascular patients. This arm of the
study was unfortunately also negative. No
cardiovascular benefits could be shown for
the primary or secondary endpoints despite
a 3% per year event rate.
These results were very disappointing
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 followup 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
1
c
levels
achieved between the standard-care and
glargine group was just 0.3%, with both
groups achieving mean HbA
1
c
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 with-
out 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 insulin and CV
and other outcomes in dysglycemia.
N Eng J Med.
Epub
11/6/2012.
DOI: 10.1056/NEJMoa1203858.
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 diabe-
tes is of paramount importance to Sanofi.
Lantus
®
(
insulin glargine [rDNA] injection)
is already supported by a wealth of available
data
1
resulting 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 poten-
tial 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 and meaningful scientific
information.
To this effect, Sanofi is working closely
with prominent scientists, health authorities
(
EU, U.S. and others), scientific associations
(
including the American Diabetes Association)
and the American Cancer Society.
At the American Diabetes Association 72
nd
Scientific Sessions, we released new results
of a large-scale epidemiological program to
evaluate cancer risk in diabetes and generate
comprehensive insulin glargine exposure data
from large databases.
Sponsored by Sanofi and conducted by inde-
pendent 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 obser-
vational program 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 scien-
tific 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 relation-
ship 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 U.S. 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:
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