Drugs & Supplements Therapy in Obesity Management

Dhani Isti - Ikhsan

Why using drugs?

I : BMI > 30 kg/m2 or BMI >27 kg/m2 w/ additional complicating factor(s)

I : Sudden weight gain 10-15 kg

• Reduced BW Maintained for 1-2 years at minimum

• Reduce <10% of BW reducing 25% risk of comorbidities

Role of drugs

• Reduce appetite

• Reduce fat absorption

• Increase energy expenditure

Reduction of comorbidities

General Precaution Contraindication

Pregnancy, breast-feeding

Unstable cardiac disease

Uncontrolled hypertension (SBP > 180 mmHg, DBP > 110 mmHg)

Unstable severe systemic illness

History of anorexia nervosa

Active severe psychiatric disorder

Other drug therapy, if incompatible (e.g. monoamine oxidase inhibitors, antimigraine drugs, adrenergic agents, drugs with arrhythmia potential)

Caution

Presence of any severe systemic illness

History of severe psychiatric disorder

Other drug therapy

Closed angle glaucoma

Age < 18 years or > 65 years

Atkinson RL. Management of obesity:pharmacotherapy. In: Kopelman PG, Caterson ID, Dietz WH (ed.). Clinical obesity in adults and children. 2nd ed. Oxford: Blackwell Publishing Ltd; 2005. p.380-9

Type of drugs

• Lipase inhibitor

– Orlistat

– Cetilistat (under development) : fewer adverse effect

• Amylase inhibitor

– α-glucosidase inhibitor (Acarbose) : only significant in type 2 diabetes patient

• Biguanid : Metformin

Type of drugs

• Hormones

– HGH :mostly reduce visceral fat (!)cardiac changes

– Testosterone: reduce visceral fat

• Adrenergic agonist

– methamphetamin

• Serotonin agonist

– Sibutramin

Orlistat

• Approved by U.S. FDA : 60 mg in package, 3x/day, may be used for BMI >25kg/m2 (WHO std)

• Mechanism of action : – Blocks the action of pancreatic lipase, reducing

tryglyceride digestion and absorption

• Benefit : – LDL reduction

Coutinho W. The first decade of sibutramine and orlistat: a reappraisal of their expanding roles in the treatment of obesity and associated conditions. Arq Bras Endocrinol Metab. 2009;53/2

Side effects

Blockage of triglyceride digestion

• Fecal fat loss & GI symptomps

• Small-significant ↓ fat-soluble vitamins (Only statistically significant for Vit. E

Contraindication • Pregnancy

• Breastfeeding

• Cholestasis

Pharmacological interaction

• Safe w/ oral contraceptive in healthy women

• Reduce cyclosporin absorpstion

?Sibutramin?

• Mech. Of action: katekolaminergik & serotoninergik

– Noradrenaline & 5-hydroxyttryptamine reuptake inhibitor increase satiety

• activation of sympathetic nervous system trough β3-adrenergic receptors increasing metabolic rates & energy expenditures

Disadvantage

• Increase heart rate, blood pressure & cardiovascular events

• Common effects:

– Insomnia, headache, dry mouth, constipation

• Serious effects : Seizure, gallstone, manic episode in bipolar pts.

• Banned by FDA since 2010

References 1. Bray GA, Van Gaal LF. Drugs that modify fat absorption and

alter metabolism. In: Bray GA, Bouchard C (ed.). Handbook of obesity: clinical applications. 3rd ed. New York: Informa Healthcare; 2008. p.315-29

2. Atkinson RL. Management of obesity:pharmacotherapy. In: Kopelman PG, Caterson ID, Dietz WH (ed.). Clinical obesity in adults and children. 2nd ed. Oxford: Blackwell Publishing Ltd; 2005. p.380-9

3. Coutinho W. The first decade of sibutramine and orlistat: a reappraisal of their expanding roles in the treatment of obesity and associated conditions. Arq Bras Endocrinol Metab. 2009;53/2

4. Sibutramine. [online] 10 Jan 2010. Diunduh dari: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601110.html

• Mediator inflamasi berlebihan merusak hormon resistensi insulin

• HGH efisiensinya (?) lipolisis & protein sintesis adiposit TG FFA & gliserol meningkat cardiovascular disease