Xenical® (Orlistat) Product and disease Overview

What is Obesity?

• Obesity is a condition where a person has accumulated so much body fat that it might have a negative effect on their health.

• If a person's bodyweight is at least 20% higher than it should be, he or she is considered obese. If your Body Mass Index (BMI) is between 25 and 29.9 you are considered overweight. If your BMI is 30 or over you are considered obese

What is Body Mass Index (BMI)?

• The body mass index (BMI) is a statistical measurement derived from your height and weight. Although it is considered to be a useful way to estimate healthy body weight, it does not measure the percentage of body fat. The BMI measurement can sometimes be misleading - a muscleman may have a high BMI but have much less fat than an unfit person whose BMI is lower. However, in general, the BMI measurement can be a useful indicator for the 'average person.

Why do people become obese?

lifestylecalories

Not sleeping enough

Endocrine disruptors

Lower rates of smoking

self-perpetuating

obesity

MedicationsObesity

gene

Eating too many calories

• These days people are eating much more food than in previous generations. This used to be the case just in developed nations - however, the trend has spread worldwide.

• Despite billions of dollars being spent on public awareness campaigns that attempt to encourage people to eat healthily, the majority of us continue to overeat.

Sedentary lifestyle

• With the arrival of televisions, computers, video games, remote controls, washing machines, dish washers and other modern convenience devices, people are commonly leading a much more sedentary lifestyle compared to their parents and grandparents.

• The less you move around the fewer calories you burn. However, this is not only a question of calories. Physical activity has an effect on how your hormones work, and hormones have an effect on how your body deals with food. Several studies have shown that physical activity has a beneficial effect on your insulin levels - keeping them stable. Unstable insulin levels are closely associated with weight gain.

• Children who have a television in their bedroom are much more likely to be obese or overweight than kids who do not, researchers from the Pennington Biomedical Research Center in Baton Rouge, LA, reported in the American Journal of Preventive Medicine (December 2012 issue).

Not sleeping enough

• Research carried out at Warwick Medical School at the University of Warwick suggested that if you do not sleep enough your risk of becoming obese doubles.. Professor Francesco Cappuccio reviewed evidence in over 28,000 children and 15,000 adults. Their evidence clearly showed that sleep deprivation significantly increased obesity risk in both groups.

• Professor Cappuccio explains that sleep deprivation may lead to obesity through increased appetite as a result of hormonal changes. If you do not sleep enough you produce Ghrelin, a hormone that stimulates appetite. Lack of sleep also results in your body producing less Leptin, a hormone that suppresses appetite

Endocrine disruptors, foods that interfere with lipid metabolism.

• A team from the University of Barcelona (UB) led by Dr Juan Carlos Laguna published a study in the journal Hepatology that provides clues to the molecular mechanism through which fructose (a type of sugar) in beverages may alter lipid energy metabolism and cause fatty liver and metabolic syndrome.

• Fructose is mainly metabolized in the liver, the target organ of the metabolic alterations caused by the consumption of this sugar.

smoking suppresses appetite

• According to the National Institutes of Health (NIH) "Not everyone gains weight when they stop smoking. Among people who do, the average weight gain is between 6 and 8 pounds. Roughly 10 percent of people who stop smoking gain a large amount of weight - 30 pounds or more."

Is obesity self-perpetuating?

• The longer a person is overweight, the harder it becomes for them to lose weight. Many have wondered whether obesity itself becomes a permanent state, i.e. does obesity promote obesity?.

• Researchers from the University of Michigan and the National Council of Science and Technology (COINCET) in Argentina, reported in the Journal of Clinical Investigation that in animal experiments, obesity seems to become a self-perpetuating state.

Obesity gene

• A faulty gene, called FTO, makes 1 in every 6 people overeat, a team of scientists from University College London reported in the Journal of Clinical Investigation (July 2013 issue).

Lead researcher, Racher Batterham, explained that people who carry the FTO gene variant tend to eat too much, prefer high-energy, fatty foods, and are usually obese. They also appear to take much longer to reach satiety (feeling of being full).

WHO 2013

The latest WHO projections indicate that at least one in three of the world's adult population is overweight and almost one in 10 is obese. Additionally there are over 40 million children under age five who are overweight.

Being overweight or obese can have a serious impact on health. Carrying extra fat leads to serious health consequences such as cardiovascular disease (mainly heart disease and stroke), type 2 diabetes, musculoskeletal disorders like osteoarthritis, and some cancers (endometrial, breast and colon). These conditions cause premature death and substantial disability.

WHO 2013

What is not widely known is that the risk of health problems starts when someone is only very slightly overweight, and that the likelihood of problems increases as someone becomes more and more overweight. Many of these conditions cause long-term suffering for individuals and families. In addition, the costs for the health care system can be extremely high.

The good news is that overweight and obesity are largely preventable. The key to success is to achieve an energy balance between calories consumed on one hand, and calories used on the other hand

What is XENICAL?

• XENICAL therapeutic category: gastrointestinal lipase inhibitor

• Indicated in conjunction with a mildly hypo caloric diet for treatment of obese patients with a BMI ≥ 30 kg/m², or overweight patients (BMI > 28 kg/m²) with associated risk factors.

• It is used to loose weight and maintain weight loss

Xenical Summary of Product Characteristics

Mode of Action of XENICAL

• Xenical binds to the lipase enzyme in the stomach and intestine and inhibits its action

• Prevents the absorption of dietary fat by 30%

• Undigested fat is eliminated in the faeces.

Xenical US Prescribing Information

Acts Non Systemically

Xenical Summary of Product Characteristics

Contraindications:

- Hypersensitivity to the active substance or to any of the excipients.- Chronic malabsorption syndrome.- Cholestasis- Breast-feeding

Dosage and Administration:

• Recommended dose of XENICAL is one capsule, 3 daily taken with water immediately before or with each main meal or up to 1 hour after the meal

• If a meal is missed or contains no fat, the dose should be skipped.

• In order to ensure adequate vitamins intake, patients following a diet should be advised to have a diet rich in fruits or vegetables and the use of multivitamin supplement could be recommended.

• When indicated multivitamins should be taken at least 2 hours after taking Xenical or before going to bed

• Xenical capsules should be stored below 250C.Xenical Summary of Product Characteristics

Efficacy of XENICAL:

• Xenical can reduce 5% to 10% of the body weight when accompanied with lifestyle modification.

• Studies have also shown its efficacy among the adolescent age group (12-16 years) with no major safety issues (except common GI adverse events).

1. Xenical Summary of Product Characteristics

2. Chanoine JP et al. Effect of Orlistat on weight and body composition in obese adolescents. JAMA. 2005;293:2873-2883

Eat less fat

Reduce meal portion size

Increase physical activity

Xenical + lifestyle modification resulted in statistically superior weight loss both in short and long term

-10.6

-6.2 -5.8

-3

-12

-10

-8

-6

-4

-2

0

1 year 4 years

Xenical +dietPlacebo +diet

LSM

wei

ght l

oss (

kg)

LSM: lean squares mean

p<0.001 p<0.001

Torgerson JS, et al. Diabetes Care 2004; 27(1):155–61.

XENDOS study

Xenical plus diet produces significantly more weight loss than diet alone in obese diabetic patients

49

2318

9

0

10

20

30

40

50

≥ 5% Weight Loss ≥ 10% Weight Loss

Xenical 120mgtid (n=139)Placebo

Percentage of patients with type II diabetes mellitus who had lost ≥5% and ≥ 10 % of initial body weight at 1 year

% o

f Pati

ents

p<0.001 p=0.017

Hollander et al. Diabetes Care 1998;21; 1288-1294

Better management of obese type II diabetes

Xenical reduces Total Cholesterol and LDL-C levels

-11.9

-4

-17.6

-7.6

-20

-15

-10

-5

0

Total Cholesterol LDL cholesterol

Xenical +dietPlacebo +diet

Mea

n Ch

ange

(%)

p<0.001 p<0.001

Muls E et al .Int J Obes Relat Metab Disor 2001;25(11): 1713-21

Safety Profile:

• Because the drug is not systemically absorbed, most adverse effects are limited to the gastrointestinal tract.

• Most commonly reported adverse events are GI symptoms : fatty and oily stools

• Generally mild, transient side effects and decrease with time.

• GI events linked to high fat intake.

Xenical Summary of Product Characteristics

Take home message!

Xenical can be used to loose weight in patients with risk factors such as type 2 DM, hypertension and hyperlipidemia.

It can be used to maintain weight loss.

Xenical has a well characterized safety profile.