VOLUME 8 NUMBER 4 • NOVEMBER 2011
179
SA JOURNAL OF DIABETES & VASCULAR DISEASE
EASD WATCH
Unfortunately, increased LDL and total
cholesterol levels might be a worry for the
future. These were also early phase 1 and 2
trials and we await new developments on
these products.
4,5
Source: 1. Viswanathan,
et al
. A randomised, double-
blind, placebo- and active-controlled, dose-ranging
study to determine the efficacy and safety of the novel
GPR40 agonist TAK-875 in subjects with type 2 diabe-
tes mellitus. Presentation 187.
2. Goodman ML,
et al
. Orally administered GPR119
agonist PSN821 shows clinically significant glucose low-
ering and other potential cardiometabolic benefits in
patients with type 2 diabetes. Presentation 188.
3. Bue-Valleskey JM. LY2599506, a novel glucokinase
activator (GKA), improves fasting and postprandial glu-
cose in patients with type 2 diabetes mellitus. Presenta-
tion 189.
4. Prince MJ, Short-term treatment with glucogon
receptor antogonist LY 2409021 effectively reduces
fasting blood glucose (FBG) and HbA
1c
in patients with
type 2 diabetes mellitus. Presentation 190.
5. Engel SS. Efficacy and safety of the glucagon receptor
antagonist, MK-0893, in combination with metformin
or sitagliptin in patients with type 2. Presentation 190
SGLT-2 inhibitors
A whole session was dedicated to selective
glucose transporter-2 (SGLT-2) inhibitors,
which are a new class of agents that inhibit
glucose re-uptake in the proximal tubule of
the nephron of the kidney. Dr Henry pre-
sented an eloquent talk on dapagliflozin
with or without metformin.
1
This was a
24-week randomised, double-blind, active
control study with 640 patients in the trial.
The results showed a 2% lowering of
HbA
1c
levels with a 5-mg combination dose
of dapagliflozin and metformin. This was
more or less equal to the 10-mg dose, where
about 3.3 kg weight loss was achieved. The
main side effects were increase in incidents
of vulvovaginitis, as well as balanitis, a slight
increase in haematocrit, and lowering in
uric acid level and systolic blood pressure of
3–4 mmHg. There were no hypoglycaemic
incidents in the study.
Another study on dapagliflozin com-
bined with metformin, presented by Dr
Bailey, was a randomised, double-blind,
placebo-controlled trial over 102 weeks.
2
Compared to the study presented by Henry,
the results was positive. The results with 5
mg dapagliflozin combined with metformin
were not as impressive (0.58% lowering in
HbA
1c
levels) as 10 mg dapagliflozin plus
metformin, which showed a 0.78% lower-
ing in HbA
1c
levels. Body weight reduction
was similar to that of the Henry study, with
a weight loss of between 2.8 and 3.4 kg.
Another new agent, empagliflozin, was
explored in studies by groups from Amer-
ica and Germany, presented by Prof Julio
Rosenstock.
3
This was a dose-finding study
in 495 patients over a period of 12 weeks.
This was compared to sitagliptin and
showed more or less equivalent HbA
1c
low-
ering of –0.6% and a 1.5-kg weight loss.
Fasting blood glucose levels were lowered
more than with sitagliptin.
Source: 1. Henry R, et al. Dapagliflozin, metformin-XR
or both together to initiate pharmacologic therapy for
type 2 diabetes. Presentation 145.
2. Bailey CT, et al. Sustained efficacy of dapagliflozin
when added to metformin in type 2 diabetes inad-
equately controlled by metformin monotherapy. Pres-
entation 146.
3. Rosenstock J, et al. ENCORE: efficacy and safety of BI
10773, a new sodium glucose co-transporter-2 (SGLT-2)
inhibitor, in type 2 diabetes patients inadequately con-
trolled on metformin. Presentation 147.
Exenatide vs liraglutide
The DURATION-6 trials evaluating exenatide
once a week versus liraglutide head to head
in a 1.8-mg dose with a 26-week follow-up
period were presented. The liraglutide was
up-titrated to a dose of 1.8 mg per day and
exenatide was used in a 2-mg per week
formulation.
The primary objective was lowering of
HbA
1c
levels after 26 weeks of follow up;
912 patients were randomised. GLP-1
analogues are known to have significant
gastrointestinal side effects and withdraw-
als on many of these trials have been
problematic in the past.
Compared to exenatide once a week,
there was slightly more withdrawals due to
side effects in the liraglutide group. How-
ever liraglutide was more effective than
weekly exenatide, which lowered HbA
1c
levels by 1.28% after 26 weeks, with a
2.68-kg weight loss (both statistically sig-
nificant). Liraglutide lowered HbA
1c
levels
1.48% with a 3.58-kg weight loss. Both of
these results were superior to the exenatide
once-a-week dosage, although with slightly
more side effects.
Both exenatide and liraglutide lowered
systolic blood pressure, as was showed in
previous trials. The side-effect profile of
liraglutide was significantly worse than the
once-a-week exenatide, but the effect was
slightly superior.
None of these agents is currently avail-
able in this form in South Africa. Liraglutide
is soon to be launched by Novo Nordisk
in our country and it is unknown when
exenatide once-a-week dosage will be
available. Both of these treatments will add
significantly to our armamentarium and are
keenly awaited.
Source: Buse JB,
et al
. Efficacy and safety of exenatide
once weekly versus liraglutide in subjects with type 2
diabetes (DURATIO-6): a randomised, open-label study.
Presentation 75.
46th Minkowski lecture
Prof Naveed Sattar fromGlasgow presented
a lecture titled ‘Exploiting biomarkers in
large datasets for insights into diabetes and
cardiovascular disease’. One of his first con-
clusions was that ALT levels, as a marker of
liver dysfunction, increase with more meta-
bolic abnormalities, while AST levels tend
to stay fairly stable. In a meta-analysis, ALT
was also shown to be a predictor of future
diabetes risk.
NAFLD (non-alcoholic fatty liver disease)
has been shown to have a 2.5 hazard ratio
for the development of diabetes. ALT was
also shown to be linked to diabetes, with a
2.02 hazard ratio for the top quartile com-
pared to the bottom quartile of ALT as a
predictor of developing type 2 diabetes.
The profile of fatty liver disease associ-
ated with diabetes is usually with ALT levels
raised more than those of AST. Gamma GT
is usually also raised, while HDL cholesterol
is low, with the patient being overweight
and glucose levels being abnormal. It was
also shown that accumulation of liver fat
could be decreased by regular exercise and
increased fibre intake.
Sattar also showed data on the complex-
ity of the interaction between adiponectin
and insulin resistance and suggested that
the association between adiponectin and
diabetes is not as simple as previously
thought. He also stated that 50 to 70% of
patients with type 2 diabetes have a variant
of fatty liver disease.
He went on to challenge the statement
that type 2 diabetes is a cardiovascular risk
equivalent, and showed data to suggest
that this is not true at diagnosis. However,
the diabetic person’s lifetime risk for cardio-
vascular disease is definitely increased and
the duration of the disease is an important
component of this risk.
He also showed that when fasting glu-
cose was used as a predictor of cardiovas-
cular risk, cardiovascular disease (CVD) only
increased when fasting glucose exceeded 6
mmol/l. Below this level, fasting glucose
was not associated with increased CVD.
Further data showed that of all the CVD
