Weight Loss Drugs

• Introduction to weight loss drugs
• Drugs that decrease food intake
  • Phentermine (Duromine)
  • Sibutramine (Reductil)
• Drugs that increase the metabolism of food
  • Orlistat (Xenical)
• Choosing the right weight loss medication
• Take home messages

Introduction to weight loss drugs

Weight loss drugs are designed to help people who are classified as obese lose weight. Obesity is an increasing epidemic in Western societies. In 2005, 18% of Australian adults were obese (approximately 3.1 million people) compared to 13% in 1995.

The main aims of obesity treatment are to:

• Lose weight;
• Maintain weight loss; and
• Prevent any further weight gain.

The most important way of obtaining these goals is developing a healthy diet and exercise regime, and developing strategies and thinking patterns that will help maintain these lifestyle changes.

For more information, see Lifestyle Changes for Obesity and Weight Loss.

For some people who are obese, weight loss with these changes alone is very difficult, and it may be beneficial to use medication to aid in initial weight loss. Large studies repeatedly report that weight loss associated with medication is greater than weight loss associated with lifestyle changes alone.

The body mass index (BMI) is a scale used to determine broad weight range categories. Weight loss medication may be prescribed to people with a BMI greater than 30 who have not adequately responded to a weight-reducing lifestyle regimen. People with a BMI of 27 who also have lifestyle risk factors may also be prescribed weight loss medication.

Risk factors for overweight patients include:

• Diabetes;
• Sleep apnoea;
• Impaired glucose tolerance;
• Smokers;
• Symptomatic osteoarthritis;
• Dyslipidaemia.

Weight loss medication is most effective for initial and short-term weight loss. Studies have shown that once people stop taking the medication, they are at risk of regaining the weight they have lost. Weight regain can have serious psychological effects associated with failure. It must be emphasised that weight regain is no reason to give up hope. Obesity is a relapsing condition and is very difficult to treat. Regaining weight is not a sign of failure, but a valuable experience that can provide motivation to try again.

Medication should only be used as an aid to lose weight. The first line of treatment should always be a diet (500–1000 kcal/day deficit) and exercise plan. Dietitians and exercise physiologists have recently been added to the Pharmaceutical Benefits Scheme (PBS) so that people who require help to change their lifestyle can receive a rebate. Medical professionals can design a diet and exercise regime specifically for a person’s lifestyle, tastes and realistic expectations of weight loss and dietary control. Tailoring the program will have a dramatic effect on the success of the regime. Combining lifestyle and pharmacological treatments can help encourage the development of a healthy lifestyle so that it is possible to maintain the weight loss when the medication is stopped.

Weight loss drugs can be classified into three broad categories:

• Drugs that decrease food intake;
• Drugs that alter the metabolism of food; and
• Drugs that increase thermogenesis (energy expenditure).

Drugs that decrease food intake

Drugs that decrease food intake, called sympathomimetic agents, suppress appetite and induce satiety earlier. Satiety is the satisfaction or “full” feeling obtained from eating. Sympathomimetic agents work on by mimicking a neurotransmitter in the brain related to appetite, called noradrenaline (NA). Sympathomimetic drugs share a similar chemical structure to NA and therefore can bind to the samereceptors as NA. They also increase NA activity in the “feeding centre” of the brain, the hypothalamus. The hypothalamus regulates the energy balance in the body. Information about energy stores is integrated in the hypothalamus, which then controls appetite and food intake. NA binding and activity in the hypothalamus has a negative effect on appetite.

Phentermine (Duromine)

Phentermine (Duromine) is the sympathomimetic anoretic available for use in Australia. Phentermine increases NA and dopamine (DA) levels in the hypothalamus, resulting in an appetite suppressant effect.

The longest phentermine (Duromine) trial, conducted in 1968, resulted in an average weight reduction of 12.6 kg over a period of 36 weeks for both continuous and intermittent use (weight loss in the placebo group was 4.8 kg). Participants also adhered to a calorie-controlled, low-carbohydrate diet regimen (1000 kcal/day).

For more information, see Phentermine (Duromine).

Sibutramine (Reductil)

Sibutramine is an appetite suppressant. It increases both NA and serotonin levels in the brain, which then bind to their receptors and exert their effects on appetite and satiety.

On average, sibutramine treatment with diet and exercise will result in 4.6 kg more weight loss than diet and exercise alone. Sibutramine (Reductil) has been approved for up to two years of use.

Along with decreasing food intake, sibutramine has been found to:

• Improve cardiocascular risk factors;
• Increase thermogenesis;
• Improve blood glucose in patients with comorbid diabetes;
• Improve central obesity (waist circumference);
• Improve levels of insulin, uric acid and C-peptide; and
• Improve lipid profile.

 

For more information, see Sibutramine (Reductil).

Drugs that increase the metabolism of food

Orlistat (Xenical)

Orlistat is a potent gastric and pancreatic lipase inhibitor. Dietary triglycerides are digested with the aid of gastric and pancreatic lipases. These lipases enzymatically break the triglycerides down into free fatty acids, which can then be absorbed in the small intestine. Pancreatic and gastric lipase inhibitors form bonds with the gastric and pancreatic lipases in the lumen of the stomach and small intestine, rendering these enzymes unable to function properly. By inhibiting the action of these lipases, the digestion of dietary fat is also inhibited and the triglycerides are excreted in faeces. Orlistat prevents approximately 30% of the dietary fat from meals being absorbed into the body (when 30% of the energy in the meals is supplied by triglycerides). After one year, the average weight loss with a combination of orlistat (Xenical) and lifestyle changes is approximately 8.5 kg.

Along with decreasing the absorption of dietary triglycerides, orlistat has been found to:

• Decrease cholesterol absorprtion and hence cholesterol levels (including LDL cholesterol);
• Have a positive effect on blood pressure;
• Improve insulin resistance; and
• Increase glycaemic control.

It is also thought that the gastrointestinal adverse effects of orlistat acts similarly to negative reinforcement, encouraging those on the medication to adhere to a low fat diet.

For more information, see Orlistat (Xenical).

Choosing the right weight loss drug

Some people will respond differently to others when taking the same weight loss drugs. Some find it difficult to adhere to the necessary lifestyle and dietary changes, whereas others simply may not respond to the medication. Everyone using weight loss medication must be assessed by their doctor within 6 weeks to 3 months of starting the treatment to determine whether it is working effectively.

Take home messages

Weight loss medication has a modest effect on weight loss. For obese people, even a modest weight loss is helpful. As little as 5–10% weight lost should be considered a success. Even if still technically overweight or obese after the weight loss, people who have lost weight will have improved lipid profiles, glucose control and insulin levels compared to others of the same BMI who have not lost weight. This decreases the health risks for diabetes, stroke, heart attack, and so on.

It cannot be stressed enough that any weight loss medication must be combined with a healthy diet and exercise plan.

More information

For more information on obesity, health and social issues, and methods of weight loss, as well as some useful tools, see Weight Loss.

 

References

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Drugs used in this treatment:

• Duromine (Phentermine)
• Xenical (Orlistat)
• Reductil (Sibutramine hydrochloride)