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- Improving diet and increasing physical activity are the main strategies for weight loss
- Weight loss medicines may be considered for some people who have not attained a healthy weight with lifestyle changes
alone, especially if they still have central obesity related risk factors
- Treatment with a weight loss medicine is only an adjunct to lifestyle change which must be maintained during and
- Medicines only produce modest reductions in weight but this may be sufficient for health benefits such as reduced
- People are likely to regain weight when medicines are stopped and there is no strong evidence that medicines are
Improving diet and increasing physical activity are the main strategies for weight loss
Healthcare professionals want patients to lose weight to improve their metabolic problems and reduce cardiovascular
(CVD) risk. Patients often want to lose weight so they can be more socially and physically comfortable. Both reasons are
valid, and the decision on how to achieve the weight loss should be worked out between healthcare provider and patient.
There are two main types of obesity
Obesity may be categorised as two different types:
- Peripheral obesity characterised by “below the waist” hip and thigh fat which is often
difficult to lose and is more common in women. Weight loss medicines have limited usefulness for this type of obesity.
- Central obesity associated with hypertension, dyslipidaemia, type 2 diabetes, CVD, sleep apnoea,
osteoarthritis, fatty liver disease and some cancers.3 Weight loss medicines including metformin may be
useful for some people in conjunction with overall lifestyle changes.
Lifestyle changes, primarily based on improvements to diet and increased physical activity, are the mainstay of weight
loss. Dietary changes may involve either a reduction in total energy intake (e.g. decreasing consumption of energy rich
foods) or modifying the types of food in the diet (e.g. reducing the fat or refined carbohydrate content of the diet or
increasing the protein content).1 These changes, along with increasing fruit and vegetable intake are far more
likely to reduce the risk of type 2 diabetes and CVD than weight loss alone.2
Increased physical activity involves undertaking moderate intensity exercise, such as brisk walking, for 30 minutes,
five or more days a week.
Target weight loss is individual however, a reduction of 5 – 10 % of original body weight is realistic. Patients should
usually aim to achieve a modest weekly weight loss (e.g. 0.5 – 1 kg) although weekly weighing is often unreliable and
may be distressing.3,4,5 A waist measurement reduction of 5 – 10% can be a more accurate predictor of health
gains as intra-abdominal fat is often lost early, especially with exercise. With increased physical activity, some people
gain weight through increased muscle mass, yet they still lose the important fat around the waist and reduce their waist
Weight loss medicines may be considered for those who have not achieved a healthy weight with lifestyle changes
Pharmacological treatment of weight loss may be appropriate as an adjunct to lifestyle interventions for some people.
A weight-loss medicine may be added to a regimen of dietary modification and increased exercise for people who have not
reached a healthy weight, still have central obesity related CVD risk factors or have reached a plateau with diet and
Body mass index and waist circumference
Body mass index (BMI) is a common way of assessing obesity in populations. It is calculated as body weight (in kg)
divided by height (in metres) squared. Body composition between people with the same BMI can be variable. BMI is not
always reliable in very old and very young people, those with a greater muscle mass or for ethnic groups with a smaller
stature (e.g. South East Asians).3,6
Abdominal circumference is a practical measure of abdominal fat and metabolic risk. Intra-abdominal fat, or visceral
fat, is associated with an increased risk of conditions such as type 2 diabetes and CVD.3 Risk is increased
with a waist circumference greater than 88 cm in women and 102 cm in men.
Generally the criteria for considering medicines for weight loss are a BMI above 30 or a BMI above 27 in the presence
of coexisting conditions such as diabetes, dyslipidaemia, hypertension or sleep apnoea.3 For people with a
BMI above 40 or above 35 with risk factors, surgical intervention may be a more appropriate option than weight loss medicines.
Orlistat (Xenical) is a lipase inhibitor that reduces dietary fat absorption by about 30%. Dietary fat is prevented
from being broken down and digested and faecal fat is increased.3,7 It is important to note that any diet involving
a reduction in total energy is associated with weight loss, not just a low fat diet.
In one meta-analysis, patients in the orlistat group lost on average 2.9 kg more weight than those in the placebo group,
and 12% more patients taking orlistat achieved greater than 10% weight loss compared to placebo.8 In both the
orlistat group and the placebo group patients were encouraged to eat a low fat diet and to exercise. This translates into
a number needed to treat (NNT) of eight which means that eight patients would need to be treated with orlistat for one
patient to lose at least 10% of their body weight.8
In the same meta-analysis and in one local study,9
significant reductions were seen in some secondary end points
such as total cholesterol, LDL cholesterol, blood pressure and fasting plasma glucose.
Gastrointestinal adverse effects, relating to orlistat’s mechanism of action, are common and experienced by about
one in four people.4 These include fatty/oily stools, faecal urgency, oily spotting and flatus with discharge.
These adverse effects are typically short-lived as patients learn to avoid high fat diets to minimise these effects. Some
patients may find it difficult to manage the three times per day regimen and adverse effect profile.
Patients taking orlistat may require supplementation with fat soluble vitamins (vitamins A, D, E, K and beta Carotene)
because a long term decrease in fat absorption may result in a decrease in their levels.6
Orlistat is not subsidised. It may be obtained on prescription or as an over-the-counter medicine from pharmacies. The
approximate cost to the patient for one month’s supply is $164.
Sibutramine has now been withdrawn from the New Zealand market. For further information,
see: http://www.medsafe.govt.nz/profs/PUArticles/WithdrawalofSibutramine.htm and
Sibutramine (Reductil) suppresses appetite and increases energy expenditure by inhibiting serotonin and noradrenaline
Sibutramine has recently been withdrawn from European markets. The Sibutramine Cardiovascular OUTcomes (SCOUT) trial
showed a 16% rise in the risk of serious, non-fatal cardiovascular events, such as stroke or myocardial infarction in
people using sibutramine. In New Zealand, Medsafe has stated that it is now reviewing the balance of risks and benefits
of using Sibutramine.11,12
For further information see BPJ
26 (Mar, 2010) “Sibutramine withdrawn from European markets”.
People taking sibutramine lose on average 4 kg more weight over one year, and an additional 18 to 25% achieve greater
than 10% weight loss at one year, compared with placebo (diet and exercise alone, NNT = 6).8,13 Sibutramine
is associated with significant reductions in triglyceride concentrations and increased concentrations of HDL cholesterol.4
Sibutramine is contraindicated in patients with inadequately controlled hypertension, coronary artery disease, congestive
heart failure, tachycardia, peripheral arterial occlusive disease, arrhythmia or stroke. Adverse effects reported by patients
include insomnia, nausea, dry mouth, constipation and anxiety. Other potentially more serious adverse effects include
an increase in heart rate and blood pressure.4
For the first three months, blood pressure and pulse rate should be measured fortnightly. Treatment should be discontinued
in patients who, at two consecutive visits, have an increase in resting heart rate of greater than 10 bpm or systolic/diastolic
blood pressure of greater than 10 mm Hg.14
Sibutramine is available on prescription only and is not subsidised. The approximate cost to the patient for one month’s
supply is $70.
Phentermine (Duromine) is an adrenergic stimulant, derived from amphetamine, that stimulates the release of noradrenaline
and reduces food intake.10
There is limited data on the long term effectiveness of phentermine, although it has been in widespread use for 40 years.
The New Zealand guideline for weight management did not find any evidence to assess the one year effect of phentermine
and it was not considered an option for long term management of weight loss.3
Compared to amphetamine, phentermine has a much lesser effect on dopamine release. In people who do not abuse drugs,
it is not stimulating or habituating, as evidenced by its continued availability. Phentermine is a controlled drug in
New Zealand and is contra-indicated in people with a history of drug or alcohol abuse.15
There are few reports of serious adverse effects with phentermine. Common adverse effects include headache, insomnia,
irritability, nervousness and palpitations.6 Phentermine is frequently used as a weight loss medicine in the
USA16 and researchers are studying combinations of phentermine with taranabant,17 topiramate18 and
bupropion for enhanced weight loss.
As there is limited data on the long-term effectiveness of phentermine, it is difficult to compare effectiveness (i.e.
NNT) with orlistat or sibutramine.
Phentermine is available on prescription only and is not subsidised. The approximate cost to the patient for one months
supply is $65 to $84 (depending on dose).
Weight loss medicines – use and interactions
||Directions for use
||120 mg three times a day with each main meal. The dose can be omitted if a meal is
missed, or if the meal contains little or no fat.
||Orlistat may alter the anticoagulant effect of warfarin; INR should be monitored. Orlistat may
also inhibit the absorption of cyclosporin and fat soluble vitamins.
||10 mg once daily, increased to 15 mg once daily if weight loss is less than 2 kg after
||Sibutramine acts on the serotonergic system therefore serotonergic medicines such as MAOIs and
SSRIs should be avoided.
||15 mg to 30 mg daily (usually 15 mg).
||Phentermine can cause hypertension therefore it is best to avoid use of other medicines that increase
blood pressure concomitantly.
Fluoxetine is sometimes considered for use as a weight loss medicine, however there is mixed evidence of its effectiveness
for this indication. Some studies have shown weight loss with fluoxetine,19 while some show no effect.20
Fluoxetine is the anti-depressant of choice for people with obesity as it is not associated with weight gain, unlike
many other antidepressants, including those in the SSRI class.
Metformin has been shown to result in minor weight loss (1 to 2 kg) compared with placebo.5,7 This degree
of weight loss is too low for metformin to be considered a weight loss medicine, however it may be a useful choice for
overweight people at high risk of diabetes.7
Metformin is an insulin sensitiser that can be used in people who have central obesity, and particularly those with “obesity-related
metabolic syndrome” or who are “pre-diabetic”. Although nausea can occur, most people can adjust dose
and timing (with meals) for comfort.
Review use of a medicine after 12 weeks if there has been a failure to achieve 5% weight reduction
Treatment should be reviewed regularly to assess effectiveness, adverse effects and adherence. These reviews should
also be used as an opportunity to reinforce lifestyle advice. Medicine therapy should only be continued beyond 12 weeks
if the patient has lost at least 5% of their initial body weight since starting. However, people with metabolic syndrome
and type 2 diabetes may lose weight more slowly so less strict weight loss goals may be appropriate in these groups.3,4
Although there has been a recent move away from using the term “metabolic syndrome” in guidelines, the
concept is still supported and the definition has been recently up-dated.21 Most people with metabolic syndrome
have central obesity.
Maintenance of weight loss is difficult
Long term maintenance of weight reduction is difficult as physiological mechanisms modify energy balance to re-establish
original body weight.10 Patients are likely to regain weight after weight loss medicines are stopped.4 It
is important that lifestyle changes to diet and exercise are continued to maintain weight loss.3 Successful
strategies include a low energy/high fruit and vegetable diet, frequent monitoring of body weight and food intake and
high levels of physical activity.10
Limited evidence for long term use of weight loss medicines
There is no strong evidence that long term use of weight loss medicines (i.e. over several years) leads to further weight
loss beyond that lost in the first year, however people receiving follow-up achieve better results.4 Studies
have shown that when patients use weight loss medicines to maintain initial weight loss they still gain weight but regain
less weight than those on placebo.3
Thank you to Dr Anne-Thea McGill, Senior Lecturer, Goodfellow Unit, Department of General Practice
and Primary Healthcare, University of Auckland and Research Clinician, University of Auckland Human Nutrition Unit for
expert guidance in developing this article.
- Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein,
and carbohydrates. N Engl J Med 2009;360(9):859-73.
- Mente A, Koning L, Shannon H, Anand S. A systematic review of the evidence supporting a causal link between dietary
factors and coronary heart disease. Arch Int Med 2009;169(7):659-69.
- Ministry of Health Clinical Trials Research Unit. Clinical guidelines for weight management in New Zealand adults.
Wellington: Ministry of Health, 2009.
- National Prescribing Centre. The drug management of obesity. MeReC Bulletin 2008;18(5).
- Bray GA, Ryan DH. Drug treatment of the overweight patient. Gastroenterol 2007;132:2239–52.
- Li M, Cheung BMY. Pharmacotherapy for obesity. Br J Clin Pharmacol 2009;68(6):804-10.
- Bray GA. Drug therapy of obesity. UpToDate 2009. Available from: www.uptodate.com
(Accessed March, 2010).
- Rucker D, Padwal R, Li SK, et al. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ
- Proietto J, Strauss BJ, Sullivan D, et al. Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes
Obes Metab 2005;7(3):254-62.
- Eckel RH. Nonsurgical management of obesity in adults. N Engl J Med 2008;358:1941-50.
- European Medicines Agency. European Medicines Agency recommends suspension of marketing authorisation for sibutramine.
Press release January, 2010. Available from: www.ema.europa.eu (Accessed
- Medsafe. Sibutramine/Reductil. Media release. Available from
- Padwal R, Rucker D, Li S, et al. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev
- Abbott Laboratories. Reductil datasheet. 2010.
- iNova Pharmaceuticals. Duromine datasheet. 2007.
- Hendricks EJ, Rothman RB, Greenway FL. How physician obesity specialists use drugs to treat obesity. Obesity 2009;17(9):1730-5.
- Addy C, Jumes P, Rosko K, et al. Pharmacokinetics, safety, and tolerability of phentermine in healthy participants
receiving taranabant, a novel cannabinoid-1 receptor (CB1R) inverse agonist. J Clin Pharmacol 2009;49(10):1228-38.
- Klonoff DC, Greenway F. Drugs in the pipeline for the obesity market. J Diab Sci Tech 2008;2(5):913-8.
- Norris SL, Zhang X, Avenell A, et al. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes
mellitus: a meta-analysis. Arch Int Med 2004;164(13):1395-404.
- Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for obesity. Drugs 2005;65(10):1391-418.
- Alberti K, Eckel R, Grundy S, et al. Harmonizing the metabolic syndrome. A joint interim statement of the International
Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart
Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study
of Obesity. Circulation 2009:1640-45.