VOLUME 9 NUMBER 3 • SEPTEMBER 2012
137
SA JOURNAL OF DIABETES & VASCULAR DISEASE
CONFERENCE REPORT
treatment of elevated blood pressure and
lipids levels to target may prevent or delay
diabetic retinopathy.
Type 2 diabetes patients are also at
great risk of neuropathy; one large cohort
indicated 59% of patients with a form of
neuropathy. Regular examination of the skin
and bone are required to detect foot ulcers
and for the assessment of neuropathy and
microvasculature. Painful polyneuropathy
is difficult to treat, with a number of
pharmacological agents recommended for
use. Adequate counselling may prevent the
development of foot ulceration.
In conclusion, Prof Mollentze recom-
mended that an annual examination include
assessment of, among others:
HbA •
1
c
level
serum lipid profile
•
blood pressure
•
weight, body mass index and waist
•
circumference
the feet
•
microalbumin level
•
serum creatinine level.
•
G Hardy
Source: Mollentze WF. What the primary healthcare
worker needs to know about the management of type
2
diabetes.
S Afr Fam Pract
2012;
54
(2):
S20–S22.
Drug Trends
ORIGIN trial shows safety and efficacy of insulin glargine: no adverse
cardiovascular outcomes after a 6.2-year follow up of early insulin use
T
he ORIGIN trial, a large trial in patients with
high cardiovascular risk and dysglycaemia,
using an intervention of initial basal insulin
(
glargine) in impaired fasting glucose (IFG),
impairedglucose tolerance (IGT) or early-stage
type 2 diabetes, has shown no cardiovascular
benefits or adverse cardiovascular outcomes.
However a reduction of progression to
diabetes did occur in patients with IFG or
IGT who were treated with insulin, actively
targeting normoglycaemia of < 5.3 mmol/l,
compared to those treated with standard
care and mainly oral agents.
1
Importantly, the long-term use of insulin
glargine was shown to be efficacious in
lowering glucose levels safely over the six-
year period. There was no increase in the
incidence of cancer or cardiovascular events
in the more than 5 000 patients treated over
this extended period.
The trial showed that better glucose
control was achieved using a daily injection
of basal insulin (with or without oral agents)
in high-risk patients who self-titrated their
insulin dosage to a fasting plasma glucose
(
FPG) level of < 5.3 mmol/l compared to
those offered standard care. However, in
both groups, a mean HbA
1
c
level of ≤ 6.5%
was achieved over the duration of the study.
In those in the glargine arm of the study,
the median insulin dose rose from 0.31 U/
kg by year one to 0.40 U/kg by year six.
Importantly, 83.6% (5 230 patients) were
adherent to their insulin glargine therapy
at year six; 19% did however permanently
discontinue their insulin therapy. In the
standard-care group, 11% of patients were
using insulin at the end of the study.
With regard to the co-primary composite
cardiovascular outcomes of death from
cardiovascular causes, non-fatal myocardial
infarction (MI) or stroke, and secondly, the
composite of these events plus either a
revascularisationprocedure or hospitalisation
for heart failure, there was no significant
difference between the two groups.
Compared to standard care, insulin
glargine, titrating towards normoglycaemia,
had a neutral outcome with regard to
cardiovascular outcomes. There was also no
significant difference with regard to micro-
vascular events. Of particular importance was
that there was no significant difference in the
incidence of any cancer, death from cancer or
cancer at specific sites (Table 1).
The incidence of a first episode of severe
hypoglycaemia was a modest 1.00 per 100
person-years in the insulin glargine-treated
group, and 0.31 per 100 person-years in the
standard-care group (
p
< 0.001). Participants
in the insulin glargine group gained a median
of 1.6 kg whereas the standard-care group
lost a median of 0.5 kg.
Reduction in progression
to diabetes
In the sub-population of 1 456 participants
without diabetes, but with IFG/IGT and other
cardiovascular risks at randomisation, 737
were assigned to insulin glargine and 719
to standard care. Those assigned to insulin
glargine were 28% less likely to develop
diabetes, as defined by oral glucose tolerance
tests performed on 65% of this cohort.
Dr Landi Lombard, specialist
physician, diabetologist, Kuilsriver,
Cape Town and editor of the
South
African Journal of Diabetes and
Vascular Disease
attended the
American Diabetes Association
meeting and commented
The ORIGIN trial had two main arms. The
first assessed the use of 1 g of omega-3
fatty acid supplementation in this cardio-
vascular high-risk group, versus placebo. This
was based on many previous trials showing
potential benefit, and the GISSI trial showing
statistically significant benefit of this therapy
in post-myocardial infarction patients, with a
15%
reduction in all-cause mortality.
A recent meta-analysis supported these
results and showed a 9% cardiovascular
mortality benefit. Unfortunately this was not
supported in the ORIGIN trial, which showed
Table 1.
Cancer incidence in the ORIGIN trial.
Insulin glargine
Standard care
Cancer by site
Hazard ratio
n
(%)
n
(%)
Breast
1.01
28 (0.4)
28 (0.4)
Lung
1.21
80 (1.3)
66 (1.1)
Colon
1.09
76 (1.2)
70 (1.1)
Prostate
0.94
88 (2.1)
89 (2.2)
Melanoma
0.88
15 (0.2)
17 (0.3)
Other
0.95
233 (3.7)
245 (3.9)
Amended from supplementary data, reference 1.
