Obesity Treatment: Drugs, Surgical Options and Popular Diets Flashcards
(36 cards)
Currently Available Options
Options:
1. Accept weight where it is
- Diet/Exercise: 3-10% weight loss
- Drugs: 5-12% weight loss
- Medically Supervised/Combination
of Diet + Drug: 10-15% weight loss - Surgery: 15-30% weight loss
Greater weight loss= greater risk and cost
There are essentially 4 options for overweight and obese people in dealing with their weight.
a. The first is to accept their weight where it is, and the likelihood that they will experience gradual progressive weight gain.
b. The second option is to try to modify their diet and/or physical activity behaviors.
c. The third option is weight loss medications and the fourth option is weight loss surgery.
d. These options go from minimal effectiveness and minimal cost/risk to maximal effectiveness and substantially greater costs/risk.
i. There is no one right approach for all patients, but in general all patients should start with diet and exercise approaches before progressing on to more aggressive treatment approaches.
e. Most people who come to see their doctor asking about weight loss medications or surgery however, have already tried diet and exercise and have reached the conclusion in that these approaches will not work for them.
When to give medications? What about surgery for obesity?
- Medications can start when BMI goes over 30
2. Surgery when BMI goes over 40… or if the BMI is 35 with a Co-morbidity
Medications that may promote weight gain:
a. Anti-diabetic medications
i. Sulfonylureas
ii. Insulin
iii. TZDs
b. Mood Stabilizers, antipsychotics
c. Birth Control Pills: Depo Provera
d. Glucocorticoids: Prednisone
PharmacologicalTreatment of Obesity
a. Current medications 5-12% wt loss
b. Benefits only last as long as patient takes the medication. Chronic treatment likely needed.
c. Drugs probably not paid for by insurance so cost is a big issue for patients.
d. Issues of FDA approval, long term safety, and efficacy.
e. Choice of mechanisms, OTC versus prescription, combinations?
Phentermine:
Large Summary
a. It is chemically related to amphetamine and increases brain norepinephrine levels. It does not have the abuse potential of amphetamine.
b. It is available as a generic and so is inexpensive ($20-40/month).
c. It is currently the most widely prescribed weight loss drug on the market, largely because of the low cost. The doses used ranges from 7-37.5 mg/day.
d. The average weight loss provided is roughly 5% of baseline weight although there is a range of responses with some people losing more and some losing no weight at all.
e. The drug acts centrally to increase satiety and thereby reduce food intake.
i. What the person experiences is fullness at the end of the meal that allows them to reduce portion sizes.
f. The primary side effects are nervousness, difficulty sleeping, headache and dry mouth.
i. The concerning side effect is an increase in blood pressure that occurs in roughly 1-2% of people taking the drug. For this reason it should not be prescribed to patients with uncontrolled hypertension.
ii. If a person has a normal blood pressure the drug should be prescribed at a low dose and the blood pressure checked 7-10 days after starting the drug to make sure it has not risen.
Phentermine: Important Points
*know for test
a. Increases NE content in the brain
b. Chemically related to amphetamine, ‘not addictive’
c. Dose: 15-37.5 mg/d,
d. Cost: $15-25.00/month Cheapest
e. FDA approved for only 3 months use
f. 5-8% weight loss
g. Side effects: hypertension, headache, nervousness
Phentermine Viewpoint
a. Most widely prescribed anti-obesity drug
b. No evidence of serious long term side effects when used as a single drug
c. Is it ethical to prescribe long term? Legally? Beneficience Non-Maleficience Autonomy
Orlistat (Xenical)
a. Pancreatic Lipase inhibitor
b. Inhibits fat absorption by 30%
c. 120 mg three times per day
d. Cost: $100.00/mo
e. GI side effects: oily stools, urgency
i. MVI (multivitamin) to prevent fat soluble vitamin deficiency
Orlistat Study
a. Thousands of patients studied up to 4 years of exposure.
b. Safest weight loss medication, approved for long term use, OTC form
c. 5-8% weight loss on average
d. May be useful in those with poorly controlled hypertension or psych problems
Orlistat (over the counter version: Alli, prescription version: Xenical)
Large Summary
a. Orlistat is a pancreatic lipase inhibitor that blocks dietary fat absorption from the GI tract.
b. The prescription dose is 120 mg taken with each meal.
i. The OTC dose is 60 mg.
c. The cost is between $90-200/ month.
d. The weight loss is similar to phentermine, about 5% of baseline weight with some patients losing more some losing less.
i. Critical*–> Safest weight loss medication, approved for long term use, OTC form
e. Since it is not systemically absorbed, there are no systemic side effects.
i. The primary side effects relate to its mechanism of action.
ii. Patients may notice oily stools, a sense of urgency, some diarrhea or oily leakage.
iii. A theoretical side effect is deficiency of fat soluble vitamins. This is not common, but it is recommended that people on this medication take a daily multivitamin.
Lorcasarin (Belviq)
Major points
*Know this for test
a. Serotonin 2C receptor agonist
b. Previous serotonin agonists fenfluramine and dexfenfluramine caused cardiac valve disease, removed from market
c. 2C receptor only in the brain not in heart
d. Studies in 1-2,000 people for up to 2 years do not show evidence if valvulopathy with lorcasarin.
e. Weight loss: 4-5% no better than phentermine or orlistat
f. Least side effects: minimal headache, dizziness and nausea
g. Cost: $220/mo
i. Unclear if physicians will prescribe off label with phentermine (no data on safety or efficacy)
Lorcasarin (Belviq)
Pros and Cons
a. Weight loss: 4-5% no better than phentermine or orlistat
b. Least side effects: minimal headache, dizziness and nausea
c. Cost: $220/mo
d. Unclear if physicians will prescribe off label with phentermine (no data on safety or efficacy)
Lorcasarin (Belviq): Large summary
know for test
Was recently approved by the FDA.
a. It is a selective serotonin 2C receptor agonist.
i. This is the latest weight loss drug that acts through serotonin.
b. The thought is that the 2C receptors are only found in the brain and not on the heart and so this newer drug will have the weight loss benefits without the cardiac toxicity.
c. Studies demonstrate that lorcasarin at a dose of 10 mg/d produces 4-5 % weight loss
i. no evidence of cardiac valve problems in patients followed out to 2 years of exposure to the drug.
d. Lorcasarin costs about $100/mo (220 according to slides) and is currently approved for long term use.
e. *The obvious question is whether lorcasarin when combined with phentermine will have a similar level of efficacy. No data currently exist to answer this question.
What is the safest weight loss medication?
Orlistat
a. Pancreatic Lipase inhibitor
i. Inhibits fat absorption by 30%
ii. 120 mg three times per day
iii. Cost: $100.00/mo
iv. GI side effects: oily stools, urgency
- MVI to prevent fat soluble vitamin deficiency
b. Thousands of patients studied up to 4 years of exposure.
c. Safest weight loss medication, approved for long term use, OTC form
d. 5-8% weight loss on average
e. May be useful in those with poorly controlled hypertension or psych problems
What is the cheapest weight loss medication?
Phentermine:
- Increases NE content in the brain
- Chemically related to amphetamine, ‘not addictive’
- Dose: 15-37.5 mg/d,
- Cost: $15-25.00/month Cheapest
- FDA approved for only 3 months use
- 5-8% weight loss
- Side effects: hypertension, headache, nervousness
Phentermine/Topiramate
*Know these major points
a. Combination gives greater efficacy with fewer side effects
b. Doses 7.5/46 mg and 15/92 mg phenterming/topiramate
c. Cost: $150.00/month
d. Side effects: dry mouth, paraesthesias, insomnia, dizziness, anxiety, irritability and disturbance in attention
Phentermine/Topiramate
Pros and Cons
a. Risk of birth defects: women need – pregnancy test on starting and monthly while using.
b. Reduces blood pressure, glucose, insulin, triglycerides and raises HDL
c. Unclear if physicians will prescribe off label using generic phentermine and topiramate.
d. Most effective medication available: 10-12% weight loss.
What causes the most weight loss?
10-12%
Phentermine/Topiramate combination
a. Combination gives greater efficacy with fewer side effects
i. Cost: $150.00/month
b. Side effects: dry mouth, paraesthesias, insomnia, dizziness, anxiety, irritability and disturbance in attention
c. Risk of birth defects: women need – pregnancy test on starting and monthly while using.
d. Reduces blood pressure, glucose, insulin, triglycerides and raises HDL
e. Unclear if physicians will prescribe off label using generic phentermine and topiramate.
Phetermine/topiramate
Large Summary
a. In a number of conditions like hypertension, diabetes and hyperlipidemia we have found that to attain a high level of efficacy, drugs acting by different mechanisms need to be combined.
b. For some time now many investigators have thought that the same principle will be needed in the treatment of obesity.
i. While a number of combination products have been tested the first to make it to market is the combination of phentermine and topiramate.
c. This combination at doses of 7.5/46 mg phentermine/topiramate and 15/92 mg each taken once daily are now available.
d. There are concerns that topiramate has teratogenic potential and its use needs to be carefully controlled in women of reproductive age.
i. Women need to have a negative pregnancy test before starting this medication and a pregnancy test needs to be documented monthly.
e. The cost is roughly $150/month.
f. *Critical: The weight loss is substantially more than with the other currently available weight loss medications and is in the range of 8-10% of baseline weight.
g. The side effects include dry mouth, paresthesias, insomnia, dizziness, anxiety, irritability and disturbance in attention.
i. The idea was that by combining low doses of these 2 medications there would be greater weight loss efficacy and fewer side effects.
Naltrexone SR/Bupropion SR
*Know these points
a. Combination of Naltrexone SR 32 mg/d and Bupropion SR 360 mg/d (NB32) or Naltrexone. (8/90 tablets, 2 BID)
b. Bupropion stimulates hypothalamic pro-opiomelanocortin (POMC) neurons reduces food intake.
c. Naltrexone blocks opioid receptor-mediated POMC auto-inhibition, augmenting POMC firing in a synergistic manner.
i. Alters reward pathways.
d. Critical*—>Intermediate in effectiveness and side effects
Naltrexone SR/Bupropion SR
Pros and Cons
a. Worrisome Side Effects: increased blood pressure and pulse, lowers seizure threshold, suicidal ideation (black box).
b. Common side effects: Nausea, constipation, diarrhea, headache, dry mouth
c. Category X in pregnancy
d. Cost $200/month
e. Stop if clinically significant increase in BP or pulse
f. Stop if <5% weight loss at 3 months
Naltrexone SR/Bupropion SR
Summary Points
a. Bupropion stimulates hypothalamic pro-opiomelanocortin (POMC) neurons reduces food intake.
i Naltrexone blocks opioid receptor-mediated POMC auto-inhibition, augmenting POMC firing in a synergistic manner. Alters reward pathways.
b. Critical*—>Intermediate in effectiveness and side effects
c. Worrisome Side Effects: increased blood pressure and pulse, lowers seizure threshold, suicidal ideation (black box).
d. Common side effects: Nausea, constipation, diarrhea, headache, dry mouth
e Category X in pregnancy
f. Cost $200/month
Naltrexone SR/Bupropion SR(Contrave):
Large Summary
a. The newest weight loss medication to be approved is the combination of the opioid receptor antagonist naltrexone with the dopamine and norepinephrine reuptake inhibitor bupropion which has mainly been used for the treatment of depression and as an aid in smoking cessation.
b. The average placebo subtracted weight loss is about 5%. It seems to be a bit more effective than phentermine and lorcasarin but less effective than phentermine/ topiramate.
c. The FDA was concerned about a very modest increase in pulse rate that was seen and asked the company to do a cardiovascular safety trial.
i. The medication has a “black box warning” about a risk of increase suicidal ideation.
d. The serious but uncommon risks are: suicidal ideation, lowering seizure threshold, increased pulse and blood pressure, and rarely increased liver function tests and closed angle glaucoma. The cost is about $150/month.
