Quick Facts on Obesity

• The incidence of obesity is rising.  
• In 2004, approximately 23% of adult Canadians were
obese & 36% were overweight.
• Reducing weight by only 5-10% can reduce the risk of
cardiovascular (CV) disease, diabetes & comorbidites.
• There is debate as to whether Body Mass Index (BMI) is
the best risk predictor for obesity as it does not take into
account fat-free mass, or the abdominal fat shown to
contribute to CV risk.  A measurement of waist
circumference or the waist:hip ratio is a better predictor
of metabolically active visceral fat and disease risk.
• “1lb (0.45kg) = 3500 calories”.  Reducing energy intake
or increasing energy expenditure by 500 calories/day will
result in losing about 1lb (½ kg) in one week. 
• 1kg weight loss Ö ~1cm decrease in waist circumference
• Removal of adipose fat tissue via liposuction does not
achieve metabolic benefits of weight loss.

Weight Loss: Other Options.

• For patients with impaired glucose tolerance (IGT),
lifestyle changes decrease the risk of developing
diabetes; however lifestyle may be hard to
maintain. Drugs such as metformin and
acarbose may also be useful for IGT/weight loss.
{Rosiglitazone ↓ progression to diabetes, but ↑HF, edema & wt.}
• Metformin is useful for obese patients with Type
2 diabetes (providing no contraindication) for its
beneficial outcomes and weight loss potential.
• Drugs known to decrease morbidity & mortality in
patients with CV risk should be considered. (e.g.
ASA, antihypertensives and statins).
• Drugs that should not be used for weight loss:
o thyroid hormone: may cause bone loss & arrhythmias
o amphetamines (eg. Adderal)
• New Drug: Rimonibant (Not yet in Canada)
o A cannabinoid (CB1) receptor blocker with favourable
changes in weight (-6kg/1yr 20mg daily) and cardiometabolic
risk factors (↓waist circumference ↓TG; ↑HDL).  Side effects
(e.g. nausea, anxiety, depression), a high drop-out rate >45%
 and lack of clinical outcome trials warrant caution.

Weight Regain With Continued Therapy

• There generally appears to be a trend towards
partial weight regain despite continued therapy.
(e.g. orlistat, XENDOS trial - Figure 1).  This may
be due in part to the natural history of aging.

Are Weight Loss Drugs Safe?

• Since 1997, 6 weight loss drugs have been
removed from the market:
o Fenfluramine  & dexfenfluramine (heart
valve abnormalities, primary pulmonary HTN);
o phenylpropanolamine (strokes in females);
o phentermine, diethylpropion, & mazindol
 (discontinued by manufacturers;
concerns with abuse and adverse events CNS & CV).
• Sibutramine was temporarily suspended from the
market in Italy, citing tachycardia, hypertension,
arrhythmia & cardiac arrest.  An increase in
BP of 1-3mmHg & heart rate of 4-5 beats/min can
result from sibutramine use; however it is unclear
if any increase in cardiovascular risk is offset by
the reduction in body weight.
• Orlistat is minimally absorbed (<5%); however,
tolerability due to GI adverse events is an issue.
{Discontinuation GI, Lab ~2x  vs placebo 8% vs 4%.}
Absorption of fat soluble vitamins is decreased,
yet remains within range (but a daily multivitamin
is recommended).  The FDA USA is considering
approving a 60mg strength for OTC sale.
• Long term safety has not yet been established.
Adverse reaction reporting is encouraged.

Do Weight Loss Drugs Work?

• In the short term, weight loss drugs may provide a
modest reduction in body weight (<5kg at 1 year;
See Table 1).
 Whether long-term outcome
benefits will result is yet to be established.
• Sibutramine & Orlistat have been shown to reduce
and, to some extent, maintain weight loss.
{No additional benefit when agents combined.}
• Drug therapy alone is insufficient as trials also
included lifestyle modification co-interventions.
• Weight regain is common upon discontinuation.

Weight Loss Therapy Options.

Lifestyle & behavioural modifications:
• Lifestyle interventions are recommended for all
overweight patients.
  They should be continued
even if medication or surgery options are used.
E.g. ŠConsider membership at a suitable gym
e.g. Curves
ŠLimit computer & TV “screen-time” for kids
Drug therapy:
• The role of weight loss drugs is of some debate.
Limited long-term effectiveness and risks must be
weighed against the complications associated with
obesity such as diabetes and heart disease.  
• A 6 month trial of diet, exercise & behavioural
therapy is recommended prior to considering drug
therapy.
  Drug therapy may be considered in
select patients: obese patients (BMI ≥30kg/m) or
those with a BMI ≥27 kg/m + 1 risk factor
(diabetes, hypertension, hyperlipidemia, coronary
artery disease or sleep apnea).  Safety, efficacy
and overall costs should be considered.
Surgery (e.g. Roux-en-Y gastric bypass or duodenal switch):
• Surgery may be considered in select patients
{obesity class III (BMI≥40 kg/m) or obesity class II (BMI 35-
39.9 kg/m) + ≥1 severe obesity related medical complications}.
• Mortality rates (generally between 0.1%-1.1%) vary
with surgery type and experience of centre.

Weight Loss Management

• Obesity is a chronic condition requiring a
long-term management plan.  
• Goals should be individualized and include weight
loss, blood pressure, blood glucose, and lipids.
• Suggested initial goal: 5-10% weight loss in 6 mo.
• Lifestyle & behavioural modifications, such as
diet & exercise, are the cornerstone of therapy.  A
multidisciplinary approach is ideal.
• Assess patients for their risk of obesity-related
health risks, weight history, previous weight loss
attempts, and current medications that may cause
weight gain (e.g. antipsychotics, antidepressants,
diabetic medications, anticonvulsants & steroids).
• Whenever possible, consider choosing drugs with
lower potential to cause weight gain.  (See bottom
notes on Weight Loss Agents Comparison Chart.)

Weight Loss Drugs. Weighing modest long-term weight loss against safety and cost.

ŠObesity and it’s associated comorbidities is increasing.
ŠWeight loss drugs provide a modest reduction in body
weight (<5kg at 1 year); weight regain is common.
ŠImprovements in metabolic risk factors may be seen.
  {e.g. ↓ progression to diabetes with orlistat in those with IGT}
ŠLong-term efficacy, safety and outcome data is lacking.
ŠPrescription, herbal and OTC agents used for weight
loss are expensive.  The 2 drugs with official weight
loss indications, Sibutramine MERIDIA and Orlistat
XENICAL, cost >$120 per month.  (Neither are
currently covered by the SK formulary or NIHB.)
ŠConsider cardiovascular risk reduction strategies such
as lifestyle interventions and drugs such as ASA,
antihypertensives and statins if indicated.
ŠMinimizing weight gain may be a consideration when
choosing drugs within certain therapeutic classes.
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IGT= impaired glucose tolerance;  OTC=over the counter products;
SK=Saskatchewan; NIHB=Indian Affairs