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OBESITY
What is obesity?
Obesity is described as an excessive amount of body fat, rather
than just excessive weight, and is a potentially serious health
problem. Some people are obese because of an underlying
medical condition, many more because their calorific intake is too
great - a behavioural, rather than a medical, problem. A person is
considered to be obese when their body mass index (BMI, defined
as body weight in kilograms divided by the square of the person's
height in metres) exceeds 30. Such people have a markedly higher
chance of death compared with others of the same age and normal
weight, owing to the link between obesity and diabetes, high
blood pressure, atherosclerosis, gall bladder disease and
some cancers.
Who does obesity affect and what does it cost?
Overweight and obesity are a problem affecting a large proportion
of the population, regardless of age and social status. In 2003,
65 per cent of men and 55 per cent of women in England had a
BMI above 25, and approximately one quarter of all children
aged 11-15 were obese.
The total cost to the NHS of treating obesity and its consequences
is estimated at £1 billion a year and the wider costs to the
community at a further £2.3-2.6 billion a year.
Present treatments and shortcomings
Three medications are currently available for the treatment of
obesity. All are used in conjunction with diet and exercise
modification. One is orlistat (Xenical, Roche) which acts within the
stomach and small intestine to prevent breakdown and absorption
of dietary fats. In clinical trials, 20 per cent of patients taking
orlistat lost 10 per cent or more of their body weight over two
years, compared with 8 per cent of patients taking placebo.
The increased fat content of the stool can, however, lead to
gastrointestinal problems such as flatulence and faecal
incontinence.
The second is sibutramine (Reductil, Abbott), which is a serotonin
and noradrenaline reuptake inhibitor. Sibutramine enhances
feelings of fullness and increases the rate at which the body burns
food. Headache, dry mouth, dizziness and constipation are the
most common adverse effects. Rapid heartbeat and raised blood
pressure are observed less frequently.
The third medication is rimonabant (Acomplia, sanofi-aventis). It is
used in obese people and those with BMI greater than 27 who
have dyslipidaemia or type 2 diabetes. The most common side
effects observed are nausea, mood alteration with depression or
anxiety and dizziness.
What's in the development pipeline?
Several cannabinoid inhibitors are in development. At Phase 3,
Pfizer is investigating CP-945,598 and Merck Sharp & Dohme is
studying MK-0364. Sanofi-aventis has a follow-up compound to
rimonabant (AVE 1625) in Phase 2 trial, while Bristol-Myers Squibb
and Solvay are collaborating on SLV 319 (also Phase 2).
Compounds interacting with this receptor system in preclinical
research include GRC 10389 (Glenmark), V24343 (Vernalis) and
E-6776 (Lab. Dr Esteve).
Two lipase inhibitors are currently in clinical trial. Alizyme has
cetilistat, which has completed two Phase 2 trials. In these trials,
cetilistat demonstrated a similar short-term (12 week) weight loss
to orlistat, but was associated with a lower level of gastrointestinal
side-effects. The other compound in development in this class is
GT 389-255 (Peptimmune), which is in Phase 1 trials.
Increasing energy expenditure would seem to be a way of
promoting weight loss, and sibutramine has long been known to
increase metabolism. A compound which does this is in Phase 2
trial: Kyorin's KRP-204. A different compound that affects fat
metabolism is AOD-9604, which is being developed by Metabolic
Pharmaceuticals, and is currently in Phase 2 trial.
Other approaches being explored are those that seek to reduce
appetite and food intake. These may act either centrally (in the
brain) or elsewhere. Centrally-acting agents include APD-356
(Lorcaserin, Arena Pharmaceuticals) at Phase 3 and NS 2330
(tesofensine, NeuroSearch), the appetite suppressant S-2367
(Shionogi), and TM30338 (7TM Pharmaceuticals) all at Phase 2,
while PRX-07034 (EPIX Pharmaceuticals), is in Phase 1 trials.
Other compounds under development that affect appetite include
three based on naturally-occurring substances: pramlintide
(Amylin), which induces feelings of fullness after eating (Phase 2),
the injectable AC-162352 (Amylin) and a nasal spray form of
PYY3-36 (Nastech), both at Phase 1.
In addition, several companies have other compounds in
development, including Merck Sharp & Dohme (MK-0493, at
Phase 2), Pfizer (CP-741,952, also at Phase 2), GSK (869682,
Phase 2 and 189075, Phase 1), Eli Lilly (five candidates due to
enter Phase 1) and AstraZeneca (AZD 1175 and AZD 2207, both
at Phase 1). With such a range of potential new medicines under
investigation, clinicians can expect to have a wider range of
treatments for the growing problem of obesity, with the potential to
prevent many future cases of obesity-related diseases.
FOR FURTHER INFORMATION CONTACT:
WEIGHT CONCERN
Brook House, 2-16 Torrington Place
London, WC1E 7HN
Phone: 020 7679 6636
Website: www.weightconcern.org.uk
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