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VOLUME 8 NUMBER 4 • NOVEMBER 2011
EASD WATCH
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Key notes on macrovascular complications
• Advanced glycation end products (AGE) are not found in higher concentrations in the
atherosclerotic plaque of diabetics, compared to patients without diabetes undergoing
carotid endarterectomy (Presentation 1264).
• An HbA
1c
level of 6.3% has the lowest risk of cardiovascular events and mortality,
according to a study of 40 000 type 2 diabetes patients in a Swedish registry
(Presentation 153).
• The use of a serum glycated albumin (GA)/HbA
1c
ratio was found to be useful in type
2 diabetes Japanese patients, with values above 3% being indicative of presence of
plaque (Presentation 1265).
• The newly developed Canadian iScore, used after ischaemic stroke, has been shown
to have a high predictive accuracy also in diabetes patients (Presentation 1254).
• In non-diabetics who are at high risk of developing diabetes, a yearly increase in the
normal HbA
1c
level (5.7%) of 0.1% was associated with an increase in aortic stiffness
comparable to being two years older (Presentation 152).
• Obesity without insulin resistance does not raise and seemed to lower cardiovascular
disease risk, according to a six-year follow-up study comparing ‘metabolically benign
obesity’ to normal-weight individuals with insulin resistance (Presentation 222).
• Non-alcoholic fatty-liver disease (NAFLD), as measured by liver ultrasound scan and
biochemically, is a major risk factor for cardiovascular events in patients with type 2
diabetes. These patients should be treated and cared for by both an internist and a
cardiologist, as their cardiovascular events are three times that of type 2 diabetes
patients without NAFLD (Presentation 246).
INCRETIN MIMETICS: THE FUTURE
OF TYPE 2 DIABETES MANAGE-
MENT
A miniature osmotic pump the size of a
matchstick may revolutionise treatment of
type 2 diabetes with insulin mimetics (and
perhaps other agents).
Once-a-year GLP-1 dosage passes
phase 2 trial
The DUROS subcutaneous delivery system
is currently being used with exenatide in
phase 2 trials. This system offers patients
and their healthcare systems a once-a-year
non-injectable exenatide, which delivers
continuous and consistent levels of this
GLP-1 agonist.
The investigational study of ITCA 650,
as it is called, has now determined a likely
dose regimen for phase 3 trials on an ini-
tial three-month ITCA 650 dosing of 20 µg/
day, followed by the subcutaneous implan-
tation of a second device for 6- and 12-µg
duration supplying 60 µg/day.
The phase 2 trial results showed con-
sistent plasma levels of exenatide up to
48 weeks with undetectable levels within
24 hours of device removal. Patients in
the trial showed sustained reductions in
HbA
1c
levels, FPG and weight reduction.
Side effects were greatly reduced and there
were no discontinuations due to nausea.
The DUROS device is also in phase 2
clinical studies in prostate cancer research,
delivering androgen reduction therapy.
Source: Luskey K,
et al
. Presentation 77. EASD Oral
Presentation
Liraglutide, the human GLP-1
analogue: safe in mild and
moderate renal impairment in
type 2 diabetes
A meta-analysis of seven clinical trials has
assessed the safety and efficacy of once-
daily liraglutide in mild (estimated creatine
clearance < 90 ml/min) renal impairment.
This review showed that reductions
in HbA
1c
levels were similar regardless of
renal impairment. The proportion of any
patients experiencing major hypoglycaemic
episodes was very low (0–0.2%) and not
related to renal function. Minor hypogly-
caemic events seemed lower in the renal-
impaired group and overall, liraglutide was
effective and well tolerated in these type 2
diabetes patients.
Source: Gough S,
et al
. Reductions in HbA
1c
and the
incidence of hypoglycaemic episodes are not affected
by renal impairment in patients with type 2 diabetes,
treated with liraglutide. Presentation 822.
Achieving weight loss with incre-
tin-based therapies, GLP-1 agonists
and DPP-4 inhibitors
This study of the data of approximately
1 200 patients treated in two large, ran-
domised trials was used to determine the
number of patients reaching the target
HbA
1c
level of less than 7% and weight loss
after 26 weeks of treatment with either
liraglutide 1.8 mg or 1.2 mg daily on top of
metformin and/or sulphonylurea therapy.
Patients receiving the higher dose of
liraglutide were most likely to reach target
HbA
1c
levels and achieve weight loss (–3 kg)
than on the other two therapies. This was a
post-hoc
evaluation, which supports avail-
able clinical trial data on these agents.
Source: Zinman,
et al
. Achieving glycaemic control and
weight loss with incretin-based therapies. Presentation
798.
Maintaining weight loss with
liraglutide on adding insulin
detemir: one-year follow-on results
The issue of weight loss in the face of
adding insulin to a type 2 diabetes patient’s
regimen is one that troubles patients and
their clinicians.
Further follow up of patients on met-
formin and liraglutide (1.8 mg) for 12 weeks
(run-in period) who were not achieving their
HbA
1c
target levels and then randomised
to continue on oral therapy (keeping HbA
1c
< 8%) or to receive 10 U insulin detemir
daily has shown no weight increase with
the addition of insulin detemir in the
following 52 weeks. Weight loss continued
in those receiving oral therapy only.
Minor hypoglycaemic rates were very
low in both arms and no major hypogly-
caemic episodes occurred in the one-year
treatment period.
Source: Bain SC,
et al
. Adding insulin detemir (I Det) to
liraglutide and metformin improves glycaemic control
with sustained weight reduction and low hypoglycae-
mic rates: 52 weeks. Presentation 73
