DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
to eight years. She was both metformin and
sitagliptin intolerant. A combination of gli-
clazide and pioglitazone resulted in weight
gain, and the introduction of exenatide over
and above these was associated with per-
sistent nausea despite improved HbA
1c
levels
and weight loss.
Switched to liraglutide, her nausea set-
tled within a day. After six months her HbA
1c
level was stable and her weight continued
to decline, at which point the pioglitazone
was discontinued. ‘She was therefore suc-
cessfully switched from exenatide to liraglu-
tide’, said Prof Schmidt.
Turning to the DURATION-6 study, he
explained that it entailed a head-to-head
comparison of once-weekly exenatide 2.0
mg to once-daily liraglutide 1.8 mg. The
subjects were a ‘normal’ population of
stable type 2 diabetes patients on various
standard treatments.
By 26 weeks, liraglutide was clearly supe-
rior in terms of its effect on HbA
1c
levels,
and there were no major hypoglycaemic
episodes. While liraglutide was associated
with more gastrointestinal side effects, he
added the concluding rider that these take
longer to manifest with exenatide and it was
too soon to draw a final conclusion in this
regard.
Getting to the root of safety
Dr Isidora Kitsou-Mylona, Novo Nordisk
regional medical advisor for the Middle East
and Africa
Dr Kitsou-Mylona addressed two major
safety concerns associated with GLP-1
analogues, namely the risks of pancreatitis
and thyroid cancer. She underscored that
those with type 2 diabetes already have an
increased risk for pancreatitis, something of
which physicians need to be aware. In the
LEAD studies, a total of seven cases was
observed, five acute and two chronic. ‘This
is consistent with what would be expected
in a background population of patients with
type 2 diabetes and is too low a number to
establish a cause-and-effect relationship’,
she said.
‘We saw an increase in c-cell thyroid
cancer in rodent models, so we monitored
this. In the human trial subjects, we saw
no increase in calcitonin levels, and there
is no evidence that liraglutide is genotoxic,
either
in vitro
or
in vivo.
C-cells are very sen-
sitive to GLP-1 and rats and mice have far
greater numbers of these cells than humans.
Because humans have fewer c-cells and
therefore fewer GLP-1 receptors, they are
not at risk of producing the calcitonin levels
seen in the animal models. The FDA agreed
with Novo Nordisk’s conclusion that the high
rodent cancer risk does not translate into a
similar risk for humans.’
She concluded by underscoring that
there was therefore no evidence to support
the suggestion that GLP-1 agonists increase
the risk of development of c-cell cancer in
humans.
Peter Wagenaar, Gauteng correspondent
Rachman
1.
J, Barrow BA, Levy JC, Turner RC. Near-
normalisation of diurnal glucose concentrations
by continuous administration of glucagon-like
peptide-1 (GLP-1) in subjects with NIDDM.
Diabetologia
1997;
40
(2): 205–211.
Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted
2.
LM, Hughes TE, Michelsen BK,
et al
. Determinants
of the impaired secretion of glucagon-like peptide-1
in type 2 diabetic patients.
J Clin Endocrinol Metab
2001;
86
(8): 3717–3723.
Zander M, Madsbad S, Madsen JL, Holst JJ. Effect
3.
of 6-week course of glucagon-like peptide 1 on
glycaemic control, insulin sensitivity, and beta-cell
function in type 2 diabetes: a parallel-group study.
Lancet
2002;
359
(9309): 824–830.
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