ANTI-OBESITY

Suharti K Suheman

Dept. of Pharmacology & Therapeutic

Med. Fac. Univ. of Indonesia

•Overweight & obesity are defined as abnormal or excessive fat accumulation that presents a risk to health

• A crude population measure of obesity is the BMI, a person’s weight (in kgs) divided by the square metres of his or her height

• A person with a BMI of 30 or > is generally considered as obese

if BMI equal to or > 25 is considered asoverweight.

• Overweight & obese are major risk factors for a number of chronic diseases, including DM, CVD & cancer

• Before it is considered as a problem only in high income peoples, but now these coditions are dramatically changes it increases in low- & middle-income peoples, particularly in urban

settings.

• Management of obesity :

* nonpharmacology ( life-style diet & special physical

exercise)

* pharmacotherapy

for longterm

• Pharmacotherapy for the management of obesity is primarily aimed at

* weight loss * weight loss maintenance &

* reduction in risk of complication recently there are : sibutramine &

orlistat. These agents : * decrease appetite * reduce absorption of fat * increase energy expenditure

• But sibutramine licenses as anti-obesity drug have been withdrawn because of their severe / serious adverse effects

• Primary endpoints to evaluate anti-obesity drugs most frequently are

: * mean weight loss

* %-age weight loss &

* proportion of patients losing 5% - 10% or > of initial BW

• Secondary endpoints :

reduction in : body fat & risk factors for CVD & the incidences of diseases such as DM

• Most pharmacotherapies have demonstrated significantly greater weight loss in patients on activetreatment than those receiving placebo (orlistat (4 years)

Orlistat is now the only drug currently approved for the long-term

management of obesity in adults

Expert opinion : Orlistat is a good choice for the th/ of obesity, because of its safety on CVD events & its positive effects on DM control, even if it is not as effective as sibutramine in reducing BW.

• Expert opinion : Orlistat is a good choice for the th/ of obesity, because of its safety on

CVD events & its positive effects on DM control, even it is not as effective as sibutramine in reducing BW.

• Lifestyle modifications such as diet & exercise intervention are essential for both prevention & management of obesity, & pharmacotherapy may be considered if the interventions are ineffective for individuals with a BMI ≥30 kg/m2 or with a BMI ≥27 kg/m2 with co-morbidities, such as hypertension or type 2 DM

• However, anti-obesity drugs have limited long-term success & the weight is regained when treatment is discontinued.

• However, anti-obesity drugs have limited long-term success &

the weight is regained when treatment is discontinued.

ORLISTAT

• a potent & reversible gastrointestinal lipase inhibitor ,preventing

dietary fat absorption by 30% by inhibiting pancreatic & gastric lipase

• is currently the only available drug for the long-term th/ of obesity, the dose

is 120 mg cap 1x / d, & a half dose (60 mg) is available asOTC in some countries, including U.S.

• several RCTs for the long-term management of obesity (4 yrs) the mean difference in weight loss due to orlistat was -2.59 kg at 6 months & -2.9 kg at 12 months , which was > than the placebo

• & other beneficial effects such as to improve several cardiometabolic parameters, blood pressure, blood glucose levels, & lipid profiles

• Pharmacokinetic : orally is minimally absorbed ; plasma level only < 5 ng/mL ; metabolism occurs mainly within the gastro-intestinal wall . Elimination : fecal excretion of the unabsorbed drug was the major route of elimination

• Side effects : GI tract : such as oily stools or oily spotting, diarrhoea, fecal incontinence, flatulence, bloating,

dyspepsia, abdominal pain; few cases of serious hepatic SE (cholelithiasis, cholostatic

hepatitis & subacute liver failure) have been reported

• Orlistat-induced BW loss seems to have beneficial effects on

bloodpressure

• However, the SEs tend to occur early & can be reduced as patients learn how to avoid fat-rich diets.

• No effect has been observed on Ca, phosphorus, Mg, iron, copper or Zn balance or on bone

biomarkers.

• Orlistat has a beneficial effect on CHO metabolism. No significant effect on cancer risk has been reported

• In May 2010 the U.S. FDA led to a label revision & the addition of a warning of severe liver injury to educate the public regarding the signs & symptoms of liver injury

• Contra-indications :

hypersensitivity to orlistat,

patients with chronic malabsorption pregnacy or breastfeeding cholestasis

• The GI tract SEs may increase , when the drug is taken with a high fat diet

• Drugs interactions : orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin & thyroxine as well as fat-soluble vitamins) affecting their bioavailability &

effectiveness