Taffy Makaya, Rebecca Poole and Kavitha Rozario
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The Past: Past Drug Therapies
Sibutramine
In considering the medical management of paediatric obesity, it is
important to first remember Sibutramine - an inhibitor of noradrenaline,
serotonin, and dopamine reuptake. This drug was withdrawn from the UK
market in January 2010 due to its association with increased cardiovascular
risk. Although the effectiveness of Silbutramine had been proved even in
adolescent trials, the SCOUT trial (Sibutramine Cardiovascular Outcomes
Trial) demonstrated that Sibutramine use in patients with cardiovascular
conditions was associated with a 16% increased risk of myocardial infarction
or stroke, although no greater risk of death overall [46]. However, due to these
risks, the European Medicines Agency suspended use of Sibutramine. The
initial use of Sibutramine and its subsequent withdrawal highlights the need
for rigorous assessment of long-term outcomes in drug development.
The Present: Current Drug Therapies in Use
The following three drugs are possibly the most commonly used anti-
obesity drugs in clinical practice within the UK – though their use for this
indication is off-label.
Orlistat
Orlistat is the most commonly prescribed drug in the medical management
of childhood obesity and is the only drug licensed by the FDA for use in
children aged 12 years and over [47]. It is not licensed in the UK, with
guidance from the Medicines and Healthcare Products Regulatory Agency
(MHRA) advising its use only in adults aged 18 and over [48]. Orlistat is
marketed in Europe as Xenical® and is available as 120mg capsules. It is also
available as 60mg capsules under the brand name ‘alli’. Orlistat works by
reducing absorption of fat - it irreversibly binds gastric and pancreatic lipases,
thereby inhibiting the hydrolysation of dietary fats into the absorbable free
fatty acids and monosaturates [49, 50]. Orlistat has a good safety record,
owing to its low systemic absorption, and it is mostly excreted in the stools
[49]. Studies show reduced fat absorption of up to 30% in patients taking
Orlistat [51].
A meta-analysis study by Viner et al. [52] looked at two randomised
controlled trials [53, 54] and concluded that combined lifestyle modifications
with Orlistat could reduce BMI by 0.83 kg/m^2 compared to placebo, with an
average weight loss of 2.3kg over a total period of 12 months. Another meta-