Obesity Treatment: Drugs, Surgical Options and Popular Diets

Question 1

Currently Available Options

Answer 1

Options:
1. Accept weight where it is

2. Diet/Exercise: 3-10% weight loss
3. Drugs: 5-12% weight loss
4. Medically Supervised/Combination
   of Diet + Drug: 10-15% weight loss
5. Surgery: 15-30% weight loss

Greater weight loss= greater risk and cost

Question 2

There are essentially 4 options for overweight and obese people in dealing with their weight.

Answer 2

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.

Question 3

When to give medications? What about surgery for obesity?

Answer 3

1. 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

Question 4

Medications that may promote weight gain:

Answer 4

a. Anti-diabetic medications
i. Sulfonylureas
ii. Insulin
iii. TZDs

b. Mood Stabilizers, antipsychotics
c. Birth Control Pills: Depo Provera
d. Glucocorticoids: Prednisone

Question 5

PharmacologicalTreatment of Obesity

Answer 5

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?

Question 6

Phentermine:

Large Summary

Answer 6

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.

Question 7

Phentermine: Important Points

*know for test

Answer 7

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

Question 8

Phentermine Viewpoint

Answer 8

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

Question 9

Orlistat (Xenical)

Answer 9

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

Question 10

Orlistat Study

Answer 10

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

Question 11

Orlistat (over the counter version: Alli, prescription version: Xenical)

Large Summary

Answer 11

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.

Question 12

Lorcasarin (Belviq)

Major points

*Know this for test

Answer 12

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)

Question 13

Lorcasarin (Belviq)

Pros and Cons

Answer 13

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)

Question 14

Lorcasarin (Belviq): Large summary

know for test

Answer 14

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.

Question 15

What is the safest weight loss medication?

Answer 15

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

Question 16

What is the cheapest weight loss medication?

Answer 16

Phentermine:

1. Increases NE content in the brain
2. Chemically related to amphetamine, ‘not addictive’
3. Dose: 15-37.5 mg/d,
4. Cost: $15-25.00/month Cheapest
5. FDA approved for only 3 months use
6. 5-8% weight loss
7. Side effects: hypertension, headache, nervousness

Question 17

Phentermine/Topiramate

*Know these major points

Answer 17

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

Question 18

Phentermine/Topiramate

Pros and Cons

Answer 18

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.

Question 19

What causes the most weight loss?

10-12%

Answer 19

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.

Question 20

Phetermine/topiramate

Large Summary

Answer 20

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.

Question 21

Naltrexone SR/Bupropion SR

*Know these points

Answer 21

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

Question 22

Naltrexone SR/Bupropion SR

Pros and Cons

Answer 22

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

Question 23

Naltrexone SR/Bupropion SR

Summary Points

Answer 23

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

Question 24

Naltrexone SR/Bupropion SR(Contrave):

Large Summary

Answer 24

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.

Question 25

Summary of Medications

*Critical points

Answer 25

a. Xenical is the safest option but limited weight loss, cost and lack of insurance coverage.
b. Phentermine is less expensive so most prescribedbut is not FDA approved for long term use.
c. Phentermine/topiramate is the most effective but costs a lot
d. Lorcasarin is only modestly effective but least side effects
e. Naltrexone/bupropion intermediate effectiveness.

Question 26

Comparison of Operations

*Know these points

Answer 26

a. Lap band: 20% weight loss, very low mortality, 1% serious or 2.4% any complication
b. Sleeve gastrectomy: 25% weight loss, 0.1% mortality, 2.4% serious or 6.3% any complication
c. Gastric bypass: 30% weight loss, 0.2% mortality, 2.5% serious or 10% any complication
* Gastric bypass has the most risk

Question 27

Surgical Options for Obesity:

Answer 27

a. There are currently 3 commonly performed weight loss operations.
i. These are the Rouxen Y gastric bypass (RYGB) operation, the laparascopic band procedure, and the sleeve gastrectomy

b. The amount of weight loss produced by these operations varies:
i. the lap band which produces roughly 20-24% weight loss
ii. the sleeve which produces 24-27% weight loss
iii. the RYGB (gastric bypass) which produces 28-30% weight loss

Question 28

The benefits of weight loss surgery include dramatic improvements in glucose control in those with pre-operative diabetes.

*Know this

Answer 28

a. In randomized controlled trials more than 40% of those individuals with type 2 diabetes pre-operatively will have resolution of their diabetes post-operatively following a RYGB (gastric bypass)
b. Improvements in glucose can occur as soon as a few days post-operatively suggesting the change in GI anatomy may foster changes in GLP-1 or other gut hormones that are important in glucose homeostasis.

Question 29

Who is a Good Candidate?

for surgery

Answer 29

a. BMI>35 kg/m2 with co-morbidities or >40 without
b. Age 20-60 (can be done in adolescents)
c. Co-morbidities: Diabetes, sleep apnea, reflux > Hypertension, DJD
d. Failed other forms of therapy
e. No serious, active cardiac, pulmonary, or psychiatric disease

Question 30

Risks of Bariatric Surgery

*Know these

Answer 30

a. Bypass: Death 0.7% (0-2%) (within 30 days) Late Death (2-3%) (within 2 years)
b. Lap Band: 0.1% death rate
c. Failure of the Surgery to Produce Weight
d. Loss (10-15%)
e. Pulmonary embolus
f. Anastamotic leaks/Sepsis
g. Thiamin Deficiency: early, vomiting, Wernike Korsakoff

Question 31

Risks and Benefits of Weight Loss Surgery:

Large Summary

Answer 31

a. These include the risk of death which is 0.7% (0-2%) (within 30 days) with the gastric bypass and less with the sleeve gastrectomy and banding procedures.
b. Late Death occurring within 2 years of surgery is roughly 2-3% following gastric bypass surgery.

c. Some patients fail to lose weight following surgery but this is uncommon accounting for only about 10-15% of all patients.
i. Others initially lose weight but then regain some weight but again this is a minority of patients and most plateau at a weight far below their baseline weight.

d. The main perioperative complications include pulmonary embolus, infections and mechanical problems such as anastamotic leaks or ulcers at the margins of anastomoses.

e. Patients who have had gastric bypass operations will need to be on a range of vitamins for the rest of their lives.
i. One of the most serious vitamin deficiencies that can occur following surgery is thiamine deficiency.
ii. Critical*–> This typically happens 3-10 weeks following surgery in association with marked vomiting. The result is Wernike Korsakoff syndrome which is a group of neurological symptoms (double vision, ataxia, altered mental status) that can progress to severe disability and even death if not diagnosed and treated.

f. Patients who have had gastric bypass operations are also at risk for deficiencies of vitamin D, iron and B12.
i. Patients who have had gastric bypass surgery should be followed indefinitely and be monitored to make sure they do not develop complications from vitamin deficiencies.

Question 32

Which Patients are Appropriate for Consideration of Drugs or Surgery?

Answer 32

The American Heart Association guidelines have specific criteria for who is appropriate for consideration for pharmacotherapy or surgical therapy of obesity.

Know this:
1. To qualify for medications patients should have a BMI>30 kg/m2 in the absence of medical conditions or a BMI>27 kg/m2 and weight related co-morbid health conditions like diabetes, hypertension, sleep apnea or degenerative arthritis.

2. To qualify for bariatric surgery patients should have a BMI>40 kg/m2 in the absence of medical conditions or a BMI>35 kg/m2 and weight related co-morbid health condition.

Question 33

Benefits of Bariatric
Surgery for T2DM

*Know this

Answer 33

a. 150 patients randomized to intensive medical therapy, gastric bypass or sleeve gastrectomy for management of type 2 diabetes
b. Average baseline A1C was 9.2%
c. 93% follow up at 12 months
d. *Saw major decrease in A1C with follow-up after surgery

Question 34

Benefits of Weight Loss Surgery

Answer 34

a. Sleep apnea: Improved in almost all
b. Hypertension: improved in half
c. Gastroesophageal reflux: improved in most
d. Urinary incontinence: improved in most

Question 35

Late Risks after Surgery

Answer 35

a. B12 Deficiency: 30% complication rate 1-9 years post operatively. 325 mg/d orally, sublingual or nasally
b. Fe deficiency: particularly menstruating women, may need parenteral Fe in some.
c. Calcium/Vitamin D deficiency, osteoporosis: monitor levels and DXA
d. Anastamotic ulcers or strictures with GBPS: may cause bleeding or Fe deficiency anemia, nausea, vomiting
e. Band Errosion/slippage with lap band
f. Depression: 20% may last 3-6 months
g. Avoid pregnancy for at least 1 year
h. Folate Deficiency: one prenatal vitamin per day

Question 36

Bariatric Surgery Summary

Answer 36

a. The most effective treatment we have for obesity.
b. *Critical–> The best treatment we have for type 2 diabetes
c. Doesn’t just restrict food intake, it is a neurohumoral treatment
d. Risk is not trivial but is falling with imrpoved methods
e. Needs lifelong followup.