VOLUME 8 NUMBER 4 • NOVEMBER 2011
183
SA JOURNAL OF DIABETES & VASCULAR DISEASE
EASD WATCH
The promise of DPP-4 inhibitors: use
them early in the disease process
An 18-month study of patients presenting
with type 2 diabetes who were not yet on
treatment has shown that initial therapy
with saxagliptin plus metformin (dual oral
therapy) achieved more sustained glycae-
mic control than monotherapy using either
of these agents.
This randomised, phase 3, double-blind
parallel group study
1
included 1 300 patients
with type 2 diabetes inadequately control-
led with diet and exercise. Patients were
randomised to oral saxagliptin 5 mg or met-
formin; 10 mg saxagliptin plus metformin;
10 mg saxagliptin; or metformin only.
The mean duration of type 2 diabetes
was 1.7 years and patients were young
(mean age 52 years). The initial dual
therapy with saxagliptin (5 or 10 mg) and
metformin consistently resulted in more
patients achieving glucose control over
18 months than those on metformin only,
regardless of the baseline characteristics of
the patient.
The results of this approach suggest that
glucose control may be more likely when
dual oral therapy is initiated early.
A second study (PROMPT) used saxaglip-
tin (5 mg/daily) instead of up-titrating met-
formin from 1.5 g/day to 2.5 g/day. The
saxagliptin addition was better tolerated
and achieved similar HbA
1c
reductions to
the larger metformin dose.
2
Source: 1. Frederick F,
et al
. Clinical characteristics and
sustained glycaemic control: a 76-week, randomised
double-blind study of saxagliptin and metformin in
treatment-naïve patients with type 2 diabetes. Presen-
tation 829
2. Hermans MP,
et al
. Effects of saxagliptin added to
sub-maximal doses of metformin compared with dose
calculation of metfomin in type 2 diabetes: results from
the PROMPT study. Presentation 828.
CARDIOVASCULAR FOCUS
IN DIABETES
Provocative suggestion: that DPP-4
inhibitors could have a cardiovascu-
lar protection affect
An evaluation of all available trials withDPP-4
inhibitors used for longer than 24 weeks in
type 2 diabetes patients was done to assess
issues of cardiovascular safety. Major cardio-
vascular events (MACE) were fewer in the
patients given DPP-4 inhibitors compared to
placebo or another treatments.
While suggesting little more than no
adverse events, this arena will require much
more attention in randomised controlled
trials for diabetes drugs, as suggested by
many cardiovascular experts.
Source: Lamanna C,
et al
. DPP-4 inhibitors and CV
events: a protective effect? Presentation 244.
Type 2 diabetes patients with non-
albuminuric renal impairment are
still exposed to coronary events
This study of 9 865 type 2 diabetes patients
from the Renal Insufficiency and Cardio-
vascular Events (RACE) trial showed that
non-albuminuric renal impairment was
more strongly associated with myocardial
infarction and the need for coronary revas-
cularisation than with stroke or the need
for carotid revascularisation. However,
patients with micro- or macroalbuminuria
had higher rates of coronary events.
Source: Pugliese G,
et al
. Association of Normoalbu-
minuric renal impairment with cardiovascular disease.
Presentation 38.
Nephropathy
In an interesting talk from the Netherlands,
Dr I Drion presented data from a study on
diabetic individuals over 75 years of age
(Zodiac-24 study) with decreased kidney
function. Estimated glomerular filtration
rate (GFR) was calculated by the MDRD and
Cockcroft-Gault formula.
It is well known that albuminuria and
decreased GFR in type 2 diabetes patients
is associated with increased cardiovascu-
lar mortality. This has not been studied
in this age group. Estimated GFR is often
decreased in this older population group.
During this study on 347 patients over 75
years, a large percentage died. The patients
were stratified into three categories, those
with estimated GFR < 45 ml/min/1.73 m
2
,
those with GFR 45–60 ml/min/1.73 m
2
and
those with > 60 ml/min/1.73 m
2
.
The study showed that patients with
albuminuria had increased risk of mortal-
ity, but not those with only GFR 45–60 ml/
min/1.73 m
2
in the age group over 75 years.
Source: Drion I,
et al
. Chronic kidney disease and mortal-
ity risk among elderly diabetic individuals (ZODIAC-24).
Presentation 37
Cardiovascular events and risk in
type 2 diabetes: the latest insights
and clinical trials
Osteoprotegerin (P-OPG) a bone-related
glycopeptide produced by vascular smooth
muscle has been shown to be a useful
independent predictor of the presence of
coronary artery disease in asymptomatic
type 2 diabetes patients with microalbu-
minuria.
This Danish study used myocardial per-
fusion imaging and CT angiography to cor-
relate the presence of arterial disease with
P-OPG levels in 200 asymptomatic type 2
diabetes patients. Importantly, patients
with low levels of P-OPG did not have sig-
nificant artery stenosis.
Source: Reinard H,
et al
. Osteoprotegerin and CAD in
type 2 diabetic patients with microalbuminuria. Presen-
tation 1283.
MICROVASCULAR COMPLICATIONS:
PERIPHERAL NEUROPATHY AND
THE DIABETIC FOOT
Peripheral neuropathy, a significant micro-
vascular complication of diabetes, leads to
impaired quality of life, and is a primary
determinant of lower-limb ulcer formation
and amputation.
In the UK, it has been found that dia-
betic patients of South Asian origin have
one-third the risk of foot ulceration com-
pared to Europeans. In an attempt to define
differences in predisposing risk factors for
ulceration, Fadayi and colleagues found
that despite worse glycaemic control,
Asian patients had better small-fibre func-
tion and structure compared to European
diabetic subjects. Furthermore, they had
higher foot skin oxygenation and hyperae-
mic blood flow response to heating, which
may protect from the development of foot
ulceration.
Source: Fadavi H,
et al
. Potential explanation for lower
incidence of foot ulceration in Asian compared to Euro-
pean patients with type 2 diabetes. Presentation 7.
Charcot foot
The mechanisms of pathological bone
resorption in acute Charcot osteo-arthrop-
athy are not fully understood. It has been
demonstrated that receptor activator of
nuclear factor
κβ
ligand (RANKL) plays an
important role as an activator of osteoclastic
resorption in acute Charcot osteo-arthrop-
athy. However, it is not known whether
RANKL-mediated osteoclastic resorption
can be modulated by the pro-inflammatory
cytokines TNF-
α
and IL-6.
Peripheral blood mononuclear cells,
which act as osteoclast precursors, were
cultured
in vitro
on bovine disks in the pres-
