Pharmacological management of obesity
The objective of the pharmacological treatment of obesity, like diet and exercise, is to decrease the amount of energy
that is consumed and/or to increase the amount of energy that is expended. However, many patients prescribed anti-obesity
medicines have limited success in achieving clinically significant and sustained weight loss, without a substantial and
ongoing commitment to lifestyle changes.
Anti-obesity medicines should be considered only as an adjunct to lifestyle interventions in patients with a BMI > 30
kg/m2 .1 Currently none of the anti-obesity medicines have been shown to reduce mortality and the long-term safety of many
of these medicines is largely unknown.21
Anti-obesity medicines currently available in New Zealand
In New Zealand the only medicines approved for use as anti-obesity agents are unsubsidised. Metformin is associated
with clinically significant weight-loss in patients with type 2 diabetes and is fully-subsidised as an anti-diabetic
medicine, however, it is not approved for use as an anti-obesity medicine.
Orlistat is a selective inhibitor of pancreatic lipase and therefore reduces digestion and absorption of fat. A patient
taking a maximum dose of orlistat, with a diet comprising 30% fat, may produce faeces with a fat content of 30%.21 Orlistat
is indicated as an adjunctive treatment of obesity in patients with a BMI greater than 30 kg/m2 .22 Orlistat is contraindicated
in patients with chronic malabsorption syndrome or cholestasis.22 Treatment may impair the absorption of fat soluble vitamins
and orlistat should be used with caution in patients with chronic kidney disease or volume depletion.22
Advise adults to take 120 mg of orlistat, immediately before, during, or up to one hour after each main meal; to a maximum
of three times daily.22 If a patient misses a meal, or they eat a meal that contains no fat, then the dose of orlistat
should be omitted.22 If a patient also requires a multivitamin then this should be taken at least two hours after a dose
of orlistat or at bedtime.22
The adverse effects of orlistat can be significant and include fatty or oily stools and other gastrointestinal symptoms
such as flatulence, cramps and bloating.22 The presence of these may indicate that the fat content of the patient’s diet
is too high and can be used as encouragement to reduce their fat intake.22 Other adverse effects include tooth and gingival
disorders, respiratory infections, malaise, headache, menstrual disturbances, urinary tract infections and hypoglycaemia.22
After one year of treatment, patients can be expected to have lost approximately 3 kg of weight.23 A systematic review
of trials over one to four years found that orlistat increased the absolute percentage of patients who were able to achieve
weight-loss of 5% of baseline by 21%, and weight-loss of 10% of baseline by 12%.24 Orlistat was also found to reduce the
onset of diabetes and to improve total cholesterol, LDL, blood pressure and glycaemic control, but increased gastrointestinal
adverse effects and slightly lowered concentrations of HDL.24
Phentermine is a dopaminergic agonist that acts as an appetite suppressant. It is indicated as a short-term, i.e. 12
weeks or less, adjunctive treatment for weight loss in patients with a BMI greater 30 kg/m2 .22 Phentermine is similar
to amphetamine and is a class C controlled drug with abuse potential. Phentermine is contraindicated in patients with:
pulmonary artery hypertension, severe cardiac disease, heart valve abnormalities or heart murmurs, moderate to severe
arterial hypertension, cerebrovascular disease, hyperthyroidism, a history of psychiatric illness, glaucoma, a history
of drug or alcohol abuse, or who have used a monoamine oxidase inhibitor within 14 days.22 Serious cardiac valvular disease
has been reported in patients taking phentermine in combination with fenfluramine or dexfenfluramine, and very rarely
primary pulmonary hypertension has been reported in patients taking phentermine alone.25
Phentermine can be prescribed at 15 – 30 mg, once daily, in the morning.22 Patients should be advised to
contact a health professional immediately if they experience symptoms such as breathlessness, chest pain, fainting,
swelling in the lower limbs, or a decreased ability to exercise.22 Prescribers are recommended to consider
withdrawing treatment of phentermine at 12 weeks if the patient has lost less than 5% of their pre-treatment
bodyweight.22 Treatment
beyond 12 weeks with phentermine may be considered for patients who are continuing to lose weight,25 if they
are able to be monitored for signs of dependence.
There are a limited number of trials assessing the effectiveness of phentermine for weight loss and the majority of
these were conducted in the 1980s. Patients taking phentermine who are eating a calorie restricted diet can expect to
lose 2 kg of bodyweight after 12 weeks and approximately 3.5 kg of bodyweight at six months.26
Due to the pharmacological similarities between phentermine and amphetamine there is considerable concern that phentermine
has addiction potential. Patients who are prescribed phentermine should be regularly monitored to ensure they are taking
the medicine appropriately and have not developed signs of aberrant behaviour. It may be helpful to establish a treatment
agreement with patients before phentermine is initiated, so that the patient has clear expectations about the goals and
end-points of treatment. It is recommended that general practitioners document the patient’s previous attempts at weight
loss before considering prescribing phentermine.
Metformin is well known as the first-line medicine in the treatment of many patients with type 2 diabetes. Metformin
decreases hepatic gluconeogenesis, improves insulin sensitivity and is able to decrease glucose absorption in the intestine.21
As many people who have diabetes are also overweight there have been a number of studies investigating the effectiveness
of metformin as an anti-obesity medicine, although it is not approved for this indication. Metformin is reported to result
in significantly greater weight-loss in patients with diabetes compared to placebo or lifestyle interventions alone, and
this weight loss is able to be maintained over a period of at least ten years.21
For further information on metformin dosing and adverse effects refer to the New Zealand Formulary.
The future of weight-loss medicines in New Zealand
The following are not currently available as weight-loss medicines in New Zealand, but are used in other countries and
may emerge as future treatment options:
Lorcaserin is a selective serotonin agonist that suppresses appetite without affecting energy expenditure.21 In three
clinical trials 38 – 48% of patients achieved at least a 5% reduction in body weight from baseline at one-year follow-up,
and 16 – 23% of patients achieved at least a 10% reduction in body weight.21 Lorcaserin is also reported to improve blood
pressure, fasting glucose and lipid levels in patients who are overweight.21 In 2012, the FDA approved lorcaserin as the
first new weight-loss medicine since 1999.21 It is recommended that patients should discontinue treatment if they have
not achieved weight loss of 5% or greater than baseline after 12 weeks.21
Phentermine and topiramate in a fixed-dose combination suppresses appetite via phentermine’s action, while topiramate
induces satiety via an unknown mechanism. Topiramate use is associated with a diverse set of adverse effects including
gastrointestinal symptoms, movement disorders and mood changes, e.g. depression or aggression.22 Several studies have
shown that using a fixed-dose combination of these two medicines for weight management results in improved tolerability
and reduced addictive potential due to the low dose of each medicine being used, e.g. phentermine 3.75 mg.21 In two trials
the mean weight loss from baseline was approximately 10% after 56 weeks of treatment, and approximately two-thirds of
patients achieved a weight loss of 5% or greater.21 Systolic and diastolic blood pressure was also found to be decreased
in patients by an average of 3 – 5 mmHg.21 In 2012, the FDA approved the use of phentermine and topiramate as a weight-loss
medicine with the proviso that prescribers receive specific training.21 In the United States, women of childbearing age
are required to take a pregnancy test before initiating treatment with phentermine and topiramate, and during every month
of treatment, due to the increased risk of foetal abnormalities.21
GLP-1 (glucagon-like peptide 1) agonists are medicines which mimic endogenous incretins that are secreted from the gut
following a meal as part of the satiety cascade. GLP-1 agonists act by increasing the secretion of insulin and decreasing
glucagon secretion. International guidelines recommend that the GLP-1 agonist exenatide should only be continued in patients
with type 2 diabetes who have experienced reductions in HbA1c and at least a 3% reduction in initial bodyweight after
six months use.27 At doses higher than that used for the treatment of diabetes, weight loss of up to 10 kg has been reported
in trials lasting for two years.23 GLP-1 treatment is associated with several adverse effects, including a possible increased
risk of acute pancreatitis and pancreatic tumours.
For further information see:
“Improving glycaemic control in people with type 2 diabetes: Expanding the primary care toolbox”, BPJ 53 (Jun, 2013).
Bariatric surgery is a last-line option for select patients
Bariatric surgery is a reasonably safe treatment option for people who are morbidly obese and have failed to achieve
clinically significant reductions in body weight by conventional management. Bariatric surgery is currently the most effective
and sustainable weight-loss treatment for people who are morbidly obese.14 Bariatric surgery can also result in improvement,
or even resolution, of type 2 diabetes and sleep apnoea.14 Weight-loss, typically at a rate of 4 kg per month is achieved
by reducing the amount of food that is consumed.14 Before patients undergo bariatric surgery they have a comprehensive
assessment to assess their suitability for the procedure that covers the patient’s dietary beliefs, behaviours, cultural
and economic background and any psychosocial issues.14
Depending on the type of procedure that is performed some degree of ongoing dietary supplementation is required following
bariatric surgery. The three most commonly performed bariatric surgeries are:14
- Adjustable gastric banding, which creates a narrowing near the gastro-oesophageal junction restricting the amount
of solid food consumed and resulting in earlier satiety. This procedure is associated with the lowest risk
of nutritional deficiency.
- Sleeve gastrectomy, where the patient’s gastric volume is decreased to approximately 15% of pre-surgery volume
- Roux-en-Y gastric bypass (RYGB) involves stapling part of the stomach to create a pouch and then dividing and attaching
the jejunum to this pouch. This procedure has a higher complication rate than other procedures.
Bariatric surgery is a major, and often irreversible, procedure. Therefore the assessment of the long-term effects on
patients is crucial. The majority of studies assessing the effectiveness of bariatric surgery do not report outcomes more
than two years after surgery or do not report outcomes from more than 80% of the original study cohort.28 There is some
evidence that gastric bypass may be more effective at producing weight-loss than gastric banding. The mean percentage
excess weight lost in the two to five years following gastric bypass was more than 50% in 11 studies, while nine of 13
studies reported a mean excess weight loss of less than 50% following gastric banding.28
Preparing patients for bariatric surgery
It is reported that 35 – 80% of people who may benefit from bariatric surgery have high-calorie malnutrition prior to
surgery.14 This may be due to a combination of poor food choices, long-term cycles of dieting, and the adverse effects
of medicines used to treat other conditions. Before bariatric surgery it is recommended that testing be performed so that
any nutritional deficiency can be identified and treated post-surgery.14 Alongside standard blood tests such as a complete
blood count and HbA1c , iron studies, vitamin B12, folic acid, vitamin D, A , E and zinc testing should be requested in
general practice.14
Two to four weeks before bariatric surgery most people are advised to start a very low energy diet involving meal replacements,
to reduce their liver volume by up to 25% and decrease the risk of complications.14 During this time there is an increased
risk of hypoglycaemia and medicines may need to be adjusted.14
Follow up after surgery
Following surgery, for one to eight weeks, the patient should aim to maintain hydration and to consume sufficient nutrients
and protein to allow healing to occur. The return to normal food can be staged as determined by patient tolerance: from
liquid, to blended and finally to solids.14 Each stage of this process should be designed by a dietitian to ensure the
patient receives adequate nutrition.14
All patients who have undergone bariatric surgery can experience diarrhoea or constipation which may be improved with
fluids, fibre and exercise.14 Adjustable gastric banding does not restrict nutrient absorption, however, eating behaviour
following this procedure does need to be modified to prevent regurgitation or blockage which can result in malnutrition
due to missed meals.14 Recurrent vomiting should be addressed urgently following surgery, particularly in the first eight
weeks following sleeve gastrectomy or RYGB, as thiamine depletion and dehydration may occur.14 Vomiting due to stenosis
or stricture may occur in 2 – 10% of patients.14 Patients who have undergone sleeve gastrectomy or RYGB may also experience
an overly suppressed appetite and dumping syndrome, where food passes through the gastrointestinal tract too quickly.14
Sleeve gastrectomy and RYGB can both result in an increased risk of nutrient deficiencies as well as hormonal and taste
changes, and for sleeve gastrectomy, increased gastric emptying.14 Following sleeve gastrectomy patients may have altered
vitamin B12 and iron utilisation and can be advised to take supplements as determined by the results of monitoring. Patients
who have undergone RYGB have altered absorption and require multivitamin, mineral and trace element supplementation at
higher doses for the remainder of their life.14
Monitoring of nutrition status should be done twice in the first year following sleeve gastrectomy and RYGB, and once
following adjustable gastric banding, then annually for each.14 Adjustable gastric banding requires the band to be adjusted
periodically, while sleeve gastrectomy and RYGB do not require specific follow up.