Anti-Obesity Drugs | Obesity

Doctors and drug manufacturers have been trying to help patients lose weight for hundreds, if not thousands, of years. Soranus of Ephesus, a Greek physician in the second century AD, used a combination of laxatives and emetics to help his patients lose weight. Patients, doctors, and drug manufacturers often overlook serious side effects in the quest for weight loss. For example, the industrial chemical, 2,4 Dinitrophenol (DNP), used for pesticides and wood preservatives, has been used by bodybuilders for fat loss since the 1980s despite being linked to at least 62 deaths.

Below are a selection of 15 drugs used to combat obesity, many of which have been discontinued or withdrawn over health concerns, along with their status in the United States as of Apr. 2014, and their side effects. Although some drugs are or were available for other uses, such as amphetamine being used in several ADHD drugs, the years on the market refer only to use of the drugs in the treatment of obesity. As of May 2014, seven of the drugs are legally available (one of these, thyroid extract, is frequently used off-label and unregulated by bodybuilders) and eight have been discontinued or withdrawn over safety concerns (three of which are still used illegally).

	1. Thyroid Extract (from sheep, pigs, cows, etc.), Thyroxin (T4), & Triiodothyronine (T3)		YEARS ON THE MARKET: 1892-present
	Status in the United States: Thyroid extract is still used, unregulated, in some bodybuilding supplements for “fat loss”; T4 is marketed under the names Synthroid, Levoxyl, Unithroid, Levothroid, and Euthyrox for indications other than weight loss (mainly hypothyroidism); T3 is marketed under the names Cytomel, Liothyronin, Tertroxin, Thybon, and Tiromel for indications other than weight loss (mainly hypothyroidism).
	Side Effects: insulin suppression, heart complications, cardiac stress, hyperthyroidism

2. 2,4 Dinitrophenol (DNP)		YEARS ON THE MARKET: 1934-1938 1980s-present (without FDA approval)
Status in the United States: DNP was discontinued in 1938 due to toxicity. This industrial chemical (used for dyes, pesticides, wood preservatives, photographic development, and explosives) is illegal for medical use but has been used by some bodybuilders for “fat loss” from the 1980s forward.
Side Effects: skin rash; cataracts; neuropathy; combination of hyperthermia, tachycardia, diaphoresis, and tachypnea eventually leading to death; 62 deaths had been attributed to DNP by 2011

3. Amphetamine		YEARS ON THE MARKET: 1947-1979
Status in the United States: A structural isomer of amphetamine, beta-methlyphenethylamine, has been found in nine dietary supplements as of Nov. 2013.
Side Effects: addiction, potential for abuse, high body temperature, cardiovascular system failure, hostility or paranoia, irregular or increased heart rate/heartbeat, increased diastolic/systolic blood pressure, increased activity, increased talkativeness, euphoria, heightened sense of well-being, decreased appetite, dry mouth, dilated pupils, increased respiration, heightened alertness and energy, nausea, headache, palpitation, alerted sexual behavior, tremor, twitching of small muscles, release of social inhibitions, toxic psychosis, physiological and behavioral disorders, dizziness, pounding heartbeat, difficulty breathing, mood or mental changes, unusual tiredness or weakness, cardiac arrhythmias, repetitive motor activity, convulsions, coma, death, ulcers, malnutrition, mental illness, skin disorders, vitamin deficiency, flush or pale skin, loss or coordination, physical collapse

4. Phentermine (Adipex-P, Suprenza, & Lonamin)		YEARS ON THE MARKET: 1959-present
Status in the United States: Available with a prescription for short-term use (may be habit-forming).
Side Effects: chest pain, decreased ability to exercise, fainting, swelling of feet or lower legs, trouble breathing, depression, drowsiness, increased blood pressure, irritability, nervousness, blurred vision, change in sexual desire, clumsiness, confusion, diarrhea, dizziness, dry mouth, headache, irregular heartbeat, nausea or vomiting, psychosis, skin rash, itching, stomach pain, unpleasant taste, hostility with the urge to attack, confusion, fever, overactive reflexes, hallucinations, tremors, trembling, panic

5. Diethylpropion		YEARS ON THE MARKET: 1959-present
Status in the United States: Available with a prescription for short-term use (may be habit-forming).
Side Effects: dry mouth, unpleasant taste, restlessness, anxiety, dizziness, depression, tremors, upset stomach, vomiting, increased urination, fast or irregular heartbeat, heart palpitations, blurred vision, skin rash, itching, difficulty breathing, chest pain, fainting, swelling of the ankles or feet, fever, sore throat, chills, painful urination

6. “Rainbow Pills”		YEARS ON THE MARKET: 1940s-1960s
Status in the United States: Discontinued. “Rainbow pills” were a combination of pills (such as digitalis, laxatives, thyroid hormones, diuretics, and amphetamines) used to treat other diseases, sometimes with an extra drug prescribed to mask the side effects of the other drugs. They were called “rainbow pills” because the combination of pills was colorful.
Side Effects: The side effects depended upon which drugs were being taken and their interactions with each other. Taking “rainbow pill” cocktails was linked to several deaths.

7. Fenfluramine (Pondimin)		YEARS ON THE MARKET: 1973-1997
Status in the United States: Withdrawn by the FDA on Sep. 15, 1997 because about 30% of patients had abnormal echocardiograms but presented no symptoms. Fenfluramine was part of the “fen-phen” drug combination when prescribed with Phentermine)
Side Effects: dizziness, dry mouth, difficulty sleeping, irritability, vomiting, diarrhea, constipation, fast/irregular/pounding heartbeat, mental and mood changes (for example, agitation, uncontrolled anger, hallucinations, nervousness), uncontrolled muscle movements, change in sexual ability or interest, severe headaches, slurred speech seizure, weakness on one side of the body, blurred vision, rare and sometimes fatal lung or heart problems

8. Dexfenfluramine (Redux)		YEARS ON THE MARKET: 1973-1997
Status in the United States: Withdrawn by the FDA on Sep. 15, 1997 because about 30% of patients had abnormal echocardiograms but presented no symptoms.
Side Effects: heart valve disease, dry mouth, dizziness, diarrhea, feeling weak, depression, eyesight problems, nausea, vomiting, spinning sensation, chronic insomnia, chills, excessive thirst, head pain, excess urination, stomach cramps, nervousness, anxiety, increased pressure of pulmonary circulation, abnormal heart rhythm, feeling faint, drowsiness, heart throbbing

9. Sibutramine (Meridia, Reductil, & Sibutrex)		YEARS ON THE MARKET: 1997-2010
Status in the United States: Withdrawn by the FDA on Oct. 8, 2010. Some weight-loss supplements illegally contain sibutramine as an ingredient.
Side Effects: increased risk of “major adverse cardiovascular events” including heart attack, stroke, and cardiovascular death; inflammation of the nose, dry mouth, incomplete or infrequent bowel movements, dizziness, chronic insomnia, loss of appetite, head pain, nervousness, easily angered, anxiety, depression, high blood pressure, painful menstruation, flu-like symptoms, visible water retention, fast heartbeat, heart throbbing, abnormal liver function tests, widening of blood vessels, throat irritation, sinus irritation and congestion, indigestion, joint pain, backache, drowsiness, excessive thirst, nausea, diarrhea, stomach cramps, numbness and tingling, feeling weak, neuroleptic malignant syndrome, serotonin syndrome, migraines, heart attack, atrial fibrillation, chronic heart failure, transient ischemic attack, stroke, burning stomach, gallbladder inflammation, interstitial nephritis, urinary tract infection, seizures, rash, trouble breathing, chest pain, potentially fatal allergic reaction, increased risk of bleeding, decreased blood platelets, mood changes, suicidal thoughts, lazy eye, abnormal dreams, hemorrhage of blood under the skin, inflammation of the voice box, bronchitis, bleeding not related to menstrual period, itching, neck pain, inflammation of the covering of the tendon, abnormal increase in muscle tone, muscle pain, leg cramps, cannot focus thoughts, loss of memory, fever, involuntary quivering, abnormal manner of walking, cough, yeast infection, vomiting, gas, high blood sugar, overactive thyroid gland, underactive thyroid, low blood sugar, anemia, confusion, altered interest in sexual activity, mania

10. Orlistat (Xenical & Alli)		YEARS ON THE MARKET: 1999-present (Xenical) 2007-present (Alli)
Status in the United States: Xenical is available with a prescription. Alli is available over-the-counter.
Side Effects: lowered absorption of vitamins, severe liver problems, kidney problems, gallbladder problems including gallstones, oily rectal discharge, passing gas with oily discharge, urgent need to have a bowel movement, oily or fatty stools, increased number of bowel movements, uncontrollable bowel movements

11. Hydroxycut Diet Supplements		YEARS ON THE MARKET: 2002-2009 2011-present (“reformulated”)
Status in the United States: Available over-the-counter. On May 9, 2009 the FDA recalled 14 products in the Hydroxycut line due to 23 reports of “serious health problems ranging from jaundice to elevated liver enzymes… to liver damage requiring liver transplant.” Hydroxycut reformulated the products and rereleased them to market in 2011.
Side Effects: 2002-2009 formulation: serious liver injuries, jaundice, elevated liver enzymes, liver damage requiring transplant, one death is known to the FDA, seizures, cardiovascular disorders, rhabdomylosis (muscle damage that can lead to kidney failure) 2001-present formulation: restlessness or jittery feeling, increased heart rate, increased blood pressure, headaches, dizziness, loss of appetite, increased swelling

12. Rimonabant (Acomplia & Zimulti)		YEARS ON THE MARKET: not applicable
Status in the United States: Rejected by the FDA in June 2007 due to increased risk of psychiatric and neurological side effects.
Side Effects: increased risk of seizures, depression, anxiety, insomnia, aggressiveness, and suicidal thoughts; five deaths and 720 adverse reactions in the UK between 2005 and 2007

13. Lorcaserin (Belviq)		YEARS ON THE MARKET: 2012-present
Status in the United States: Approved by the FDA on June 27, 2012. The drug was previously rejected by the FDA on Oct. 23, 2010 because the FDA required more testing of the drug.
Side Effects: serotonin syndrome, neuroleptic malignant syndrome, headache, dizziness, fatigue, nausea, dry mouth, constipation, valvular heart disease, changes in attention or memory, depression, suicidal thoughts, painful erections, slow heart beat, decreased blood cell count, increase in prolactin, cough, back pain (specific to diabetic patients: low blood sugar)

14. Phentermine & Topiramate (Qsymia, formerly Onexa)		YEARS ON THE MARKET: 2012-present
Status in the United States: Approved by the FDA on July 17, 2012. The drug was previously rejected by the FDA on Oct. 28, 2010 due to safety concerns because Phentermine is one half of the formerly popular “fen-phen” combination (the other half, Fenfluarmine, was pulled from the market in 1997).
Side Effects: birth defects including cleft lip/palate; depression; mood problems; insomnia; concentration, memory, and speech difficulties; metabolic acidosis; low blood sugar in people with type 2 diabetes; seizures; kidney stones; decreased sweating; fever; paresthesia (tingling in hands, arms, feet, or face); dizziness; dysgeusia (change in the way foods taste or loss of taste); constipation; dry mouth

15. Bupropion & Naltrexone (Contrave)		YEARS ON THE MARKET: not applicable
Status in the United States: In phase 3 clinical trials. Previously rejected by the FDA on Jan. 31, 2011 because of concern about cardiovascular safety.
Side Effects: nausea, constipation, and vomiting in patients with type 2 diabetes; other side effects unclear as of Apr. 25, 2014

Sources:

Jillian Ball, “Diet Pills with Amphetamines,” www.livestrong.com, Oct. 21, 2013

Belviq, “Belviq Prescribing Information,” www.belviq.com, Aug. 2012

George A. Bray, “History of Obesity,” Obesity: Science to Practice, Eds. Gareth Williams and Gema Frühbeck, 2009

George A. Bray, “Some Historical Aspects of Drug Treatment for Obesity,” Pharmacotherapy of Obesity, Ed. John P.H. Wilding, 2008

P.A. Cohen, A. Goday, and J.P. Swann, “The Return of Rainbow Diet Pills,” American Journal of Public Health, Sep. 2012

FDA, “Akyuz, Sinan 11/16/09 – Warning Letter,” www.fda.gov, Nov. 16, 2009

FDA, “Calories Count: Report of the Working Group on Obesity,” www.fda.gov, Mar. 12, 2004

FDA, “Early Communication about an Ongoing Safety Review Orlistat (Marketed as Alli and Xenical),” www.fda.gov, Aug. 24, 2009

FDA, “FDA Announces Withdrawal FenFluramine and Dexfenfluramine (Fen-Phen),” www.fda.gov, Sep. 17, 1997

FDA, “FDA Approved Obesity Drugs,” www.fda.gov (accessed July 21, 2011)

FDA, “FDA Approves Belviq to Treat Some Overweight or Obese Adults,” www.fda.gov, June 27, 2012

FDA, “FDA Drug Safety Communication: FDA Recommends against the Continued Use of Meridia (sibutramine),” www.fda.gov, Oct. 8, 2010

FDA, “Medication Guide: Qsymia,” www.fda.gov, 2013

FDA, “Questions and Answers about FDA’s Initiative against Contaminated Weight Loss Products,” www.fda.gov, Sep. 3, 2013

FDA, “Warning on Hydroxycut Products,” www.fda.gov, May 1, 2009

Tse-Ling Fong, MD, et al., “Hepatotoxicity Due to Hydroxycut: A Case Series,” American Journal of Gastroenterology, July 2010

J. Grundlingh, P.I. Dargan, M. El-Zanfaly, and D.M. Wood, “2,4-dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death,” Journal of Medical Toxicity, Sep. 2011

Alok, K. Gupta and Frank L. Greenway, “Safety of Obesity Drugs,” Obesity: Epidemiology, Pathophysiology and Prevention, Eds. Debasis Bagchi and Harry G. Preuss, 2007

Debra Henn and Deborah DeEugenio, Diet Pills, 2009

P. Hollander, A.K. Gupta, R. Plodkowski, F. Greenway, H. Bays, C. Burns, P. Klassen, and K. Fujioka, “Effects of Naltrexone Sustained-Release/Bupropion Sustained-Release Combination Therapy on Body Weight and Glycemic Parameters in Overweight and Obese Patients with Type 2 Diabetes,” Diabetes Care, Dec. 2013

Hydroxycut, “Homepage,” www.hydroxycut.com (accessed July 21, 2011)

Jason Kane, “New Weight Loss Pill Gets Second Look from FDA, Stirring Old Fears,” www.pbs.org, Feb. 22, 2012

Medline Plus, “Diethylpropion,” www.nlm.nih.gov, Nov. 20, 2012

National Center for Biotechnology Information (NCIB), “Diethylpropion,” PubMed Health database, www.ncbi.nlm.nih.gov, Sep. 1, 2008

National Center for Biotechnology Information (NCIB), “Phentermine,” PubMed Health database, www.ncbi.nlm.nih.gov, Jan. 1, 2011

Amy Norton, “Hydroxycut Linked to Other Cases of Liver Damage,” www.reuters.com, Feb. 12, 2010

Orexigen, “FDA Issues Complete Response to New Drug Application for Contrave(R) for the Management of Obesity,” www.orexigen.com, Feb. 1, 2011

Phentermine.com, “Side Effects,” www.phentermine.com (accessed Apr. 22, 2014)

Andrew Pollack, “Abbott Labs Withdraws Meridia from the Market,” www.nytimes.com, Oct. 8, 2010

Andrew Pollack, “F.D.A. Rejects Qnexa, a Third Weight-Loss Drug,” www.nytimes.com, Oct. 28, 2010

Andrew Pollack, “No F.D.A. Approval for New Diet Pill,” www.nytimes.com, Oct. 23, 2010

Robert Pool, Fat: Fighting the Obesity Epidemic, 2001

Steven Reinberg, “Possible Reason for Rimonabant’s Side Effects Discovered,” www.consumer.healthday.com, Mar. 24, 2008

Phillip Strange, “DNP: The Return of a Deadly Weight-Loss Drug,” www.theguardian.com, Feb. 6, 2014

Mark Subsinsky, “The Butterfly Effect: The Basics of the Thyroid, Part 2,” www.bodybuilding.com, May 4, 2005

University of Maryland Center for Substance Abuse Research, “Amphetamines,” www.cesar.umd.edu, Oct. 29, 2013

WebMD, “Drugs & Medications – Meridia Oral,” www.webmd.com (accessed Apr. 23, 2014)

WebMD, “Drugs & Medications – Phentermine,” www.webmd.com (accessed Apr. 23, 2014)

David S. Weigle, “Pharmacological Therapy of Obesity: Past, Present, and Future,” Journal of Clinical Endocrinology & Metabolism, June 2003

Xenical, “Important Safety Information,” www.xenical.com, 2012

Alison Young, “Nine Diet Supplements Contain Amphetamine-Like Compound,” www.usatoday.com, Nov. 18, 2013

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