1. Prescription Medications David L. Gee, PhD Professor of Food Science and Nutrition Central Washington University

2. Major Categories of Weight Loss Drugs Appetite Suppressants Inhibitors of Nutrient Absorption (Metabolic Stimulants)

3. Appetite Suppressants: Serotonergic Drugs Mechanism of action – elevated levels of serotonin reduce appetite Serotonin levels increase after eating serotonergic drugs –Increase release of serotonin

4. Serotonergic Drugs A shaky history Fenfluramine Dexfenfluramine (Redux) 1997 FDA withdrew approval status – Heart valve damage – Primary pulmonary hypertension

5. Appetite Suppresants: Noradrenergic Drugs Mechanism of Action – elevation of norepinephrine – associated with satiety Eating increases norepinephrine noradrenergic drugs

6. Noradrenergic Drugs Phentermine Phenylpropanolamine – Dexatrim, Acutrim, PPA – Also as decongestant in cold medications – OTC – FDA warnings ( 2004) hemorrhagic stroke removing PPA from all products

7. Drugs that increase both serotonin and norepinephrine Sibutramine (Meridia) – increases serotonin and norepinephrine by inhibiting their re-uptake – FDA approval 1997

8. Sibutramine (Meridia) Mean wt loss: 10-14 pounds – effects vary substantially Side effects: – hypertension – dry mouth – headache – constipation no sign of heart valve problems or PPH

9. Sibutramine (Meridia) FDA regulations – affect manufacturers’ advertisement/promotion – does NOT regulate how physicians prescribe – for obese clients (BMI>30) or – for overweight clients with health risks (BMI>27) – safe for one year use

10. Combined Drug Treatment fen/phen – fenfluramine/phenteramine – “off label use” – FDA: not tested for safety or effectiveness – Fenfluramine banned – Other combinations: Ephedra-phenteramine

11. Inhibitors of Nutrient Absorption Orlistat (Xenical) – FDA approved 1999 – pancreatic lipase inhibitor inhibits absorption of dietary fats causes steatorrhea may psychologically reduce fat/caloric intake

12. Inhibitors of Nutrient Absorption Dietary Supplements – Chitin (fat malabsorption) – Starch Blockers (alpha amylase inhibitors) – like all dietary supplements: not tested for safety or effectiveness not “approved” by FDA

13. Metabolic Stimulants Thyroid Hormone – only useful if TH deficient (rare) – results in significant LBM loss Ephedra – dietary supplement – FDA investigating adverse effect claims regulatory status in question

14. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int. J. Obesity & Related Met. Dis. 27:1437-1446 (2003) RCT’s published between 1966-2002 – Double blind RCT of > 1 yr – BMI > 30 + comorbidities – Only two drugs w/ studies meeting these criteria Orlistat/Xenical (11 studies, n=6021, mean BMI=35.7, predominantly white females) Sibutramine/Meridia (3 studies, n=929, mean BMI=33.4, predominantly white females)

15. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Orlistat (Xenical) Mean weight loss = 2.7 kg – 2.9% greater than placebo – 12% lost > 10% of body weight 33% attrition rate Reductions in serum lipids, serum glucose, blood pressure, lower HDL-C Gastro-intestinal side effects

16. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Sibutramine (Meridia) Mean weight loss = 4.3 kg – 4.6% wt loss – 15% lost > 10% of body weight 48% attrition rate Lower reductions in serum lipids than orlistat Increased blood pressure and pulse rate