Home' Australian Pharmacist : April 2011 Contents Vol. 30 -- April #04
old drug new indication
Bromocriptine -- from Parkinson's
disease to diabetes?
By Dr Lisa Nissen
Non-insulin Dependent Diabetes
Mellitus (NIDDM) or Type 2 diabetes
has been described by some as a '21st
Century plague' affecting around 4%
of all Australians (900,000 people).
NIDDM carries a significant public
health and social burden and is one of
the top 10 causes of death in Australia.
NIDDM is a chronic condition that
affects the way our bodies metabolizes
glucose. NIDDM develops when the
body becomes resistant to the effects
of insulin (losses the ability to control
the movement of sugar into cells) or
when the pancreas stops producing
enough insulin. Left untreated, the
consequences of NIDDM can be life-
The initial symptoms of NIDDM are
often subtle, leaving many patients
in the community completely
unaware that they have the condition.
Symptoms include: increased thirst
and frequent urination, increased
hunger, unplanned weight loss,
fatigue, blurred vision and slow
healing of sores or infections. It's clear
that certain factors increase the risk,
however, including: weight, inactivity,
family history, race, age, presence
of pre-diabetes and a history of
gestational diabetes. NIDDM affects
many major organs, including: blood
vessel disease (e.g. heart attack and
stroke), nerves (neuropathy), kidney's
(nephropathy), and the eyes (e.g.
diabetic retinopathy). Controlling blood
glucose levels can help prevent these
and other serious complications.
There is no cure for NIDDM, and
although diet and exercise are
important steps in the management
of the condition, often medication
management forms the mainstay for
treatment of the condition. Many of
these treatments focus on improving
the utilisation of endogenous insulin,
or in the case of insulin treatment,
providing a direct substitute. The
prevalence of NIDDM in the community
Dr Lisa Nissen is Associate Professor (QUM),
at the School of Pharmacy, University of
Queensland and Deputy-Director, Centre for
Safe and Effective Prescribing (CSEP).
and the limitations of current
treatments has driven the need for and
investigation of other therapeutic agent
for the treatment of the condition. One
of these is Bromocriptine.
Bromocriptine is an ergot alkaloid D2
(dopamine) receptor agonist that has
been used extensively in the treatment
of hyperprolactinaemia, galactorrhoea
and Parkinsonism. It is known that
hypothalamic hypodopaminergic states
and disturbed circadian rhythm are
associated with the development of
insulin resistance, obesity and diabetes
in animals and humans. Thus, when
Bromocriptine is given early in the
morning at the start of the light phase,
it appears to act centrally to reset
circadian rhythms of hypothalamic
dopamine and serotonin and improve
insulin resistance and other metabolic
Although the exact mechanism of
action in humans is still to be clarified,
in animals it acts centrally to reduce
resistance to insulin-mediated
suppression of hepatic glucose output
and tissue glucose disposal while also
reducing hepatic triglyceride synthesis
and free fatty acid mobilisation,
manifesting as decreases in both
plasma triglycerides and free fatty
acids. These effects are supported by
the results of Phase II and III clinical
studies which showed that a Quick-
Release Bromocriptine (Cycloset)
lowered HbA1c and fasting blood
glucose levels in study participants.
The dose of Bromocriptine used for
the treatment of NIDDM is much
lower than for Parkinson's disease,
as such the medication regimen is
generally better tolerated. In clinical
trials the commonly reported adverse
events included nausea, fatigue,
vomiting, headache, and dizziness
with these being more likely to
happen when patients first started
taking the medication.
The new Quick-Release Bromocriptine
product Cycloset has been approved
for use in NIDDM by the FDA.
Bromocriptine does not currently
have an approval for the treatment of
NIDDM in Australia; however it does
give us some indication of options for
treatment that may be available for
patients in Australia in the future.
• Pijl H, Ohashi S, Matsuda M, et al.
Bromocriptine: a novel approach to the
treatment of type 2 diabetes. Diabetes
Care. 2000 Aug;23(8):1154--61.
• Scranton R, Cincotta A. Bromocriptine
-- unique formulation of a dopamine
agonist for the treatment of type 2
diabetes. Expert Opin Pharmacother.
• Holt RI, Barnett AH, Bailey CJ.
Bromocriptine: old drug, new
formulation and new indication.
Diabetes Obes Metab. 2010
• Scranton RE, Gaziano JM, Rutty D,
Ezrokhi M, Cincotta A. A randomized,
double-blind, placebo-controlled trial
to assess safety and tolerability during
treatment of type 2 diabetes with usual
diabetes therapy and either Cycloset or
placebo. BMC Endocr Disord. 2007 Jun
• Gaziano JM, Cincotta AH, O'Connor
CM, Ezrokhi M, Rutty D, Ma ZJ,
Scranton RE. Randomized clinical trial
of quick-release bromocriptine among
patients with type 2 diabetes on overall
safety and cardiovascular outcomes.
Diabetes Care. 2010 Jul;33(7):1503--8.
Epub 2010 Mar 23.
1.25 mg once or twice daily; increased gradually
10--30 mg daily (in divided doses) according to
Type II diabetes
Quick-release Bromocriptine: Initially, 0.8 mg
administered once daily within two hours after
waking in the morning. Increasing to a maximum of
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