Pharmacotherapy is indicated in addition to behavioural intervention in overweight people with a weight-related health problem, or people with obesity
Four medications are approved by the Therapeutic Goods Administration (TGA) for the treatment of obesity in Australia
Gastrointestinal devices are a relatively new weight loss therapy and an emerging field of research
Bariatric surgery is the most efficacious long-term treatment for severe obesity and should be considered with regard to individual circumstances
This page has been written by Dr Priya Sumithran, Associate Professor Tania Markovic and Associate Professor Samantha Hocking; and reviewed by Professor Ian Caterson.
Overweight and obesity have complex biological, psychosocial and environmental determinants, and are not simply the result of a poor lifestyle. Behavioural intervention, including changes in eating habits and physical activity, is the foundation of obesity management. The resulting weight loss, however, sets in motion a long-lasting, counter-regulatory biological response, including a reduction in total energy expenditure greater than expected for the amount of lean mass lost, an increase in appetite, and changes in several hormones which influence energy balance,12 which amounts to a physiological defence against weight loss. It is therefore not surprising that obesity, like other chronic conditions, is not ‘cured’ by the initial phase of treatment (in this case, weight loss), and requires long-term, multidisciplinary management.
Treatment guidelines recommend consideration of additional therapies such as pharmacotherapy and bariatric surgery when behavioural intervention alone has not achieved sufficient weight loss to improve health or quality of life.34
Pharmacotherapy is indicated in addition to behavioural intervention in overweight people (BMI ≥ 27 kg/m2) with a weight-related health problem, or people with obesity (BMI > 30 kg/m2). In conjunction with behavioural intervention, pharmacotherapy may be useful in inducing weight loss, or preventing weight regain. Four medications are approved by the Therapeutic Goods Administration (TGA) for the treatment of obesity in Australia (Table 1) – phentermine, orlistat, liraglutide and naltrexone-bupropion. With the exception of orlistat, which reduces absorption of ingested calories, the medications used to treat obesity primarily act via effects on appetite (reducing hunger and/or increasing satiation).
The choice of medication is dependent on individual factors and preferences. There are very few randomised studies of phentermine monotherapy, or comparisons of the available medications against each other, but clinical trials indicate that on average, the available agents have similar weight loss efficacy, of around 4–6% over 12 months (Table 1). There is considerable variation between individuals in treatment response: in an analysis of randomised clinical trials of people with and without T2D who used liraglutide, naltrexone-bupropion and orlistat at the recommended doses for ≥1 year, weight loss of 5% or more was achieved by (respectively) 63, 55 and 44% of participants (compared with 23% of placebo participants) and ≥10% weight loss occurred in 34, 30 and 20% of participants after 12 months’ use (compared with 9% of placebo).5 It should be noted that some of the studies included in this analysis used very intensive behavioural interventions, and weight outcomes in both placebo and active intervention groups are often better in clinical trials compared with real-world results.
Weight loss of 5% is sufficient to bring about an improvement in weight-related complications. See Health benefits of weight loss. All of the available medications are associated with improvements in cardiometabolic risk profile, although each medication has favourable effects on different risk factors, and none is consistently superior.6 Liraglutide and orlistat are associated with reductions in fasting glucose, HbA1c (a measure of average blood glucose), risk of developing type 2 diabetes, and blood pressure; orlistat has the greatest effect on reducing low-density lipoprotein (LDL) cholesterol, and naltrexone-bupropion is associated with a moderate increase in high-density lipoprotein (HDL) cholesterol.6
Data on long-term safety and effectiveness of obesity medication are limited, but since the compensatory biological response to weight loss is long-standing, it is expected that treatment is required over the long-term, as is the case for other chronic conditions. It is recommended that medications are discontinued if they are ineffective after 12 weeks of the maximum tolerated dose, or if there are significant or persistent adverse effects.7
Equitable access to obesity medications is lacking, as none are subsidised under the Pharmaceutical Benefits Scheme (PBS). There are no cost-effectiveness analyses for use of these medications in the Australian context.
|Table 1: Medications approved for the treatment of obesity in Australia||Phentermine (Duromine® Metermine®)||Liraglutide (Saxenda®)||Naltrexone-Bupropion (Contrave®)||Orlistat (Xenical®)|
|Average weight loss (above behavioural intervention alone)||6% at 20 weeks ||6% at 1 year ||5% at 1 year ||4% at 1 year |
|Proportion of participants with 5% and 10% weight loss at 1 year||Not reported||63 and 33% (vs 27 and 11% with behavioural intervention alone)||48 and 25% (vs 16 and 7% with behavioural intervention alone)||73 and 41% (vs 45 and 21% with behavioural intervention alone)|
|Common side effects||Hypertension, palpitations, tachycardia, insomnia, dry mouth, restlessness||Nausea, vomiting, diarrhoea, constipation, abdominal pain, increased heart rate||Nausea, headache, tachycardia, hypertension, insomnia, dry mouth||Steatorrhoea, oily spotting, fat-soluble vitamin deficiency|
|Other||Recommended for short-term (maximum 12 week) use||Risk of developing type 2 diabetes reduced by 79% in people with pre-diabetes at 1 year||Risk of developing type 2 diabetes reduced by 45% in people with pre-diabetes at 4 years|
Over-the-counter weight loss supplements
There are a plethora of non-prescription weight loss supplements and herbal medicines available for sale in pharmacies and supermarkets in Australia and sales suggest that they are widely consumed. They promise easy weight loss but there is no evidence that any of these products are of any value to assist weight loss and some may be counterproductive or potentially unsafe.12
Gastrointestinal devices are a relatively new weight loss therapy and an emerging field of research. They are usually inserted endoscopically and result in weight loss that is generally greater than that achieved with medication but less than with surgical procedures.
One of the first such procedures was the gastric balloon but this needs to be removed after 6 months (after which weight regain usually occurs) and there have been life threatening complications with some of the devices (e.g. perforation of the oesophagus or stomach, pancreatitis, death), which have been withdrawn.
The EndoBarrier™ is a thin plastic sleeve that lines the first 60 cm of the small intestine such that food can longer be absorbed here resulting in weight reduction. However, the device needs to be removed within 12 months of insertion.
Aspiration therapy involves the placement of a small tube with an access port in the stomach that allows the patient to remove 30% of ingested calories after each meal. This treatment is safe and surprisingly effective as it modifies eating behaviour.
One of the newer procedures is the endoscopic sleeve gastrectomy in which stitches are placed inside the stomach to reduce its capacity by 70%. Complications are infrequent but can be severe and include gastrointestinal bleeding and fluid leak or collection from the stomach. These procedures usually result in 15% weight loss.
Bariatric surgery should be considered as part of a comprehensive multidisciplinary treatment program taking into account the individual situation. National guidelines recommend bariatric surgery for adults with:
- BMI >40 kg/m2
- BMI >35 kg/m2 with comorbidities expected to improve with weight loss, and
- BMI >30 kg/m2 with type 2 diabetes and inadequate glycaemic control despite optimal medical treatment.313
The three most common bariatric procedures in Australia are the sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB). The choice of procedure depends on the individual goals of treatment, available expertise (surgeon and institution), patient preferences, and personalised risk stratification.14 There have been considerable improvements in the safety of bariatric surgery over recent decades, partly due to the increasing use of laparoscopic procedures, and perioperative mortality rates are now less than 0.3%.15
Bariatric surgery is the most efficacious long-term treatment for obesity. LAGB achieves a mean weight reduction of 15–20% at 1 year, and larger weight losses of around 25–30% are seen with SG and RYGB.16 17 As with all obesity treatments, there is considerable inter-individual variation in response: more than half of people who undergo RYGB will have weight loss of 25% or more at 1 year. Some weight regain (on average 5–10% at 10 years) is expected in the longer term.18
Bariatric surgery also results in marked improvements in most weight-related health conditions, particularly type 2 diabetes (T2D), after RYGB and SG, and to a lesser extent, LAGB. In a meta-analysis of randomised controlled trials comparing surgery with medical treatment of T2D in 463 patients with follow-up of at least 2 years, diabetes remission was seen in 53% of bariatric surgery participants compared with 4% of participants who did not undergo surgery.19 In four studies with 5 years’ follow-up, diabetes remission was seen in 28% of surgical and 4% of medically-treated participants.19 Available evidence from observational cohort studies indicates a lower risk of microvascular events (damage to eyes, kidneys and nerves) after bariatric surgery compared to non-surgical treatment in people with T2D after at least 5 years’ follow-up,20 and of cardiovascular events and overall mortality in people with and without diabetes.21 Surgical treatment of obesity is also associated with improvements in cardiometabolic risk factors and numerous other weight-related issues such as obstructive sleep apnoea,22 non-alcoholic fatty liver disease,23 cancer incidence,24 sexual function25 and quality of life, particularly physical wellbeing.26
As with medical treatment of obesity, there is inequitable access to bariatric surgery in Australia. The potential demand for bariatric surgery far outstrips supply – it was estimated that of the 3.35 million Australians with obesity aged 18 to 65 years in 2011–2013, more than one quarter were potentially eligible for bariatric surgery (accounting for 6% of the population aged 18–65 years), of whom nearly half (46%) did not have private health insurance and 35% resided outside a major city.27 In 2014–15, there were just over 22,700 weight loss surgery procedures performed in Australia, the vast majority of which (88%) occurred in private hospitals. A meta-analysis of 61 studies concluded that overall, bariatric surgery is cost saving over the life course, even without considering indirect costs such as reduction in medication usage.28