Discuss the historical uses of weight loss agents in

the US

Evaluate the Rx approved agents for Weight loss

Assess the Rx agents that has the potential to cause weight loss

Gauge the natural medicines that can be used for weight loss

Objectives

History

Mid 1900’s

Late 1930s - 1950s:

Doctors began prescribing amphetamines for its side effect of appetite suppression

1959:

Phentermine approved by the FDA

1960’s:

"Rainbow pill" regimes were being used. They were a combination of multiple pills to help weight loss, such as amphetamines, diuretics, and laxatives.

1965:

Appetite suppressant aminorex fumarate was developed as treatment for obesity.

Withdrawn from the market two years later due to pulmonary hypertension side effects.

1970’s

1970:

Adderall® was used as a diet drug, marketed under the name Obetrol.

1973: the Food and Drug

Administration approved the drug fenfluramine

FDA began the recall of diet drugs containing amphetamines.

1979: Fenfluramine and phetermine

have been combined into Fen-Phen® and gained popularity.

1990’s

1992

Fen-Phen® gained more popularity when a report stated that it caused a 10% weight loss.

1994 Dietary Supplement Health and Education Act is passed, which

adds the "dietary supplement" category.

Ephedra classified as a herb and use for weight loss increases.

1995

Dexfenfluramine (Redux®) was developed as an alternative to fenfluramine with less side-effects.

1990’s

1997

Removal of Fen-Phen® is called for by the FDA after reports linking fen-phen with heart valve problems.

Redux® removed from the market due to similar problems relating to cardiovascular health.

1998

Meridia® is put on the market.

2000’s

2004: Ephedra removed from the US market from concerns with

raising blood pressure which could lead to strokes and death.

2009

Hydroxycut® diet supplements pulled off the market after reports of liver damage.

Meridia® (sibutramine) is removed from the US market from concerns that it could raise blood pressure and cause stroke or heart attack.

2000’s

2010

Orlistat (prescription as Xenical®, over-the-counter as Alli®) is available.

Orlistat is taken to reduce the amount of dietary fat that is absorbed by the digestive tract.

Medications Approved for Weight Loss

MOA: sympathomimetic amine (amphetamine)

Dose: IR- 25mg TID-QID once hour before meals CR- 75mg once a day

Weight Loss: 6.6 lbs. in 6-12 months

AE: pulmonary Hypertension, valvular heart disease, dependence

CI: pulmonary hypertension, hypertension, hyperthyroidism, glaucoma, MAOIs

DI: MAOI, alcohol, anesthetics,

Cautions: consider cardiac evaluation. d/c 4 weeks if not effective.

Diethylpropion (Tenuate®, Tenuate® Dospan®)

MOA: Adrenergic- increase norepinephrine levels

Approved for short term use

Dose- 18.75-37.5 mg before breakfast or 1-2 hours after breakfast or 18.75mg BID

Weight loss- 7.92 lbs 2-24 weeks

AE: over-stimulation and nervousness, insomnia, and headache

DI: alpha adrenergic blockers, SSRI, MAOIs,

CI: PPH, valvular heart disease, symptomatic cardiovascular disease, glaucoma, moderate hypertension

Phentermine (Adipex®, Ionomin®, Fastin®)

• Basic Function: Prevents the absorption of fats,

reducing caloric intake Inhibits pancreatic lipases

which break down fat molecules

• Dose: 160mg TID with meals • Weight loss: 7.6 lbs/5% of

baseline fat at 1 year • OTC version: Alli® Half the dose of prescription

• DI: cyclosporine, warfarin, lowers absorption of many medicaitons and fat soluable vitamins

Side Effects: Oily discharge/fatty stools

Liver failure

Orlistat (Xenical®, Alli® OTC)

Rx used or studied off-label weight loss

Dose-300-400 mg per day divided twice daily

Weight loss- 6.1 lbs in obese patients with depression 6-12 months

AE: dry mouth, nausea, CNS stimulation, tremor, seizures, increased BP

CI: seizure disorder, bulemia, MAOIs

Cautions: drugs that decrease seizure threshold, Strong CYP2D6 inhibitor

Bupropion(Wellbutrin SR®)

Dose-5-10mcg SQ twice daily, 1 hour prior to two main

meals, al least 6 hours apart

Weight loss: 5.94-6.38 lbs over 24 weeks in diabetes patients in diabetes trials

AE: N/V, hypoglycemia, renal impairment, HA

CI: hypersensitivity to exenatide

DI: APAP, anti-infective agents, sulfonylureas, lovastatin

Caution: lower dose if coadministration with sulfonylurea, renal impairment. Do not use if have severe GI disease such as gastroparesis

Exenatide (Byetta®)

Dose: 125 IU IM once daily, plus fat-free 500 Kcal per

day diet

Weight loss- no reliable evidence

AE: ovarian hyperstimulation, edema, HA, depression , fatigue, arterial thromboembolism

CI: precocious puberty, prostate cancer, androgen-dependant cancer,

Cautions: heart disease, renal impairment, seizure disorders, migrane, and asthma

Human Chorionic Gonadotropin (Novarel®, Pregnyl®)

Dose- 60-120 mcg just before major meals (250 kcal or

30g carbohydrate)

Weight loss- 3.74 lbs after 6 months

AE: severe hypoglycemia, N/V, allergic reactions

CI: gastroparesis, hypoglycemic unawareness,

Cautions: May delay drug absorption (may need to separate dose especially for drugs requiring rapid onset)

Pramlintide (Symlin®)

Dose- Variable; most commonly about 100-200 mg

per day divided twice daily

Weight loss- 6.5% baseline wieght loss in 6 months

AE- paresthesia, dysgeusia, irritability, constipation, dry mouth, hyperammonemia,

CI: hypersensitivity

Caution- d/c slowly to prevent seizures, dosage adjustment for renal insufficiency, decreased efficacy of OC

Topiramate (Topamax®)

Dose- 100-600mg daily or divided twice daily based

on response and no faster increase of 100mg every 2 weeks.

Weight loss- 5% of baseline weight loss in 16 weeks

AE: serious skin an dhematologic reactions, mood disorders, psychosis, cognitive impairment, somnolence, dizziness, headache, agitation

Cautions: teratogen, avoid if CrCL<50 ml/min, CYP3A4 substrate

Zonisamide (Zonegran®)

Natural Medicines for Weight loss

5-Hydroxytryptophan

5-HTP is the precursor to serotonin.

MOA: increase seratonin levels to decrease appetite or cause a feeling of fullness or satiety

Made from L-tryptophan, a natural amino acid found in most dietary proteins

Three studies show appetite reduction and weight loss with 600-900mg daily (avg. 11 lbs. In 12 weeks)

SE: GI effects, linked to Eosinophilia Myalgia Syndrome (EMS)

DI: anything that increases seratonin levels (ie SSRI)

called "fat burning" drugs that increase energy

expenditure

Lots of patients try herbal products touted as "natural" thermogenic enhancers. Patients are often enticed by their savvy brand names...Metabolife...Slenderite...GlycoLEAN Accelerator 2...Fen-Tastic...Naturally Herbal Phen...Thermo Sculpt...and on and on.

Most contain Ephedra but with the FDA controversy some were replaced with bitter orange and Hoodia

Thermogenic agents

Ephedra/Ephedrine

Ephedra: plant with 2 active constituents: Ephedrine

Pseudoephedrine

Ephedrine is normally paired with caffeine in OTC diet supplements

Basic function of Ephedrine: Appetite suppressant

Acts on adrenergic receptors

Weight loss of 0.9kg/month for up to 6 months

Dose: 15-20mg three times daily

Side Effects: High blood pressure

Heart attacks, strokes (can be fatal)

Tremors/seizures

Insomnia

Banned by FDA Drugs now contain

“legal ephedra”

Epehdra without ephedrine

DI: caffeine, QT prolongation, stimulants,

South African spiny succulent plant

MOA: Increases hypothalamic ATP

It's claimed that the San Bushmen eat hoodia to stave off hunger during long hunts.

Effectiveness: No published scientific evidence demonstrating use as appetite suppressant

AR: none reported

DI: none reported

Dose: no typical dose

Hoodi gordonii

Contains 1-6% synephrine

(adrenergic agonist related to ephedrine) Dose of 150mg daily

Essential oil from an type of orange

Similar health concerns and SE as ephedrine

Lack of evidence about effectiveness

DI: It is a CYP3A4 Inhibitor, MAOIs, SSRI, QT prolonging drugs,stimulants,

Bitter Orange

Chitosan

Made from chitin, the main component of crustacean shells (e.g. shrimp, crab, lobsters)

No scientific data confirming its effects as a “fat blocker” or “fat binder” or in promoting weight loss

0.5kg weight loss 1-6 months. Dose: 1-5 grams/day

AR: gi upset, nausea, flatulance, consti

Pation

DI: warfarin

Barley 3-6 grams

barley oil extract, flakes, flour

Digestion Inhibitors

Blond psyllium- 6-12 grams daily

Caution: Theoretically fiber can reduce the absorption of some drugs by reducing GI transit time.

Both Not well studied for weight loss

7-Keto

7-keto DHEA-metabolite of DHEA MOA: Boosts basal metabolism and

thermogenesis In one double bind study, participants were

given either 7-keto or placebo for 8 weeks along with 1800 kcal diet and exercise 3x/week for 45 minutes.

6.34 pounds lost vs 2.3 pounds Increased weight loss associated with higher

levels of T3 Dose: 100mg bid AR: decreased hemoglobin and hematocrit DI: None known

MOA: theorized that CLA might shrink adipose tissue by

inducing apoptosis of fat cells. Also seems to reduce hunger and improve satiety and feeling of fullness

AR:gastrointestinal upset including diarrhea, nausea, loose stools, and dyspepsia

Dose: CLA 0.7-4.5 grams/day seems to significantly decrease body fat mass (BFM) and might increase lean body mass (LBM) in some patients

Caution: Some evidence indicates that the isolated trans-10, cis-12 isomer of CLA increases hyperproinsulinemia and insulin resistance in patients with abdominal obesity.

Conjugated Linoleic Acid

Adults and children with low calcium intake are

more likely to gain weight, have a higher body mass index (BMI), and be overweight or obese compared to people with higher calcium intake

intake of 800-1200 mg seems to increase weight reduction, lean body mass, and body fat loss

Some evidence suggests that increasing calcium consumption by 900-1000 mg/day is associated with an 8-9 kg reduction in body weight

Calcium

People are using it for related for hyperlipidemia,

diabetes, and obesity.

American diets are deficient in chromium, which leads to diabetes, weight gain, and other metabolic abnormalities.

MOA: evidence that chromium can help reduce lipid and glucose levels in patients with diabetes

chromium picolinate produces modest weight loss of about 1.1 kg compared to placebo over 72-90 days

AR: cognitive, perceptual, and motor dysfunction, headaches, insomnia, sleep disturbances, irritability, and mood changes

Chromium

AKA “African Mango” or “bush mango” a tree from

Africa that produces a mango-like fruit MOA: seeds have high soluble fiber content and function

as a bulk-forming laxative. reduces the accumulation of fat in fat cells called adipocytes

in several weight loss products such as Integra-Lean, Vitagetics Vita Lean, Dr. Sears Private Label Primal Force Primal Lean etc.

Clinical research shows that taking a standardized seed extract (IGOB131) 150 mg twice daily for 10 weeks reduces weight by about 13 kilograms compared 0.7 kilograms in overweight patients taking placebo.

AR: flatulence, headaches, and difficulty sleeping DI: none known

Irvingia gabonensis

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