Drugs- Obesity

Question 1

list 4 sympathomimetic amines for obesity

Answer 1

Benzphtamine
Diethylpropion
Phendimetrazine
Phentermine

Question 2

orlistat

Answer 2

lipase inhibitor

Question 3

phentermine/topiramate ER

Answer 3

sympathomimetic amine/antiepileptic combo

Question 4

lorcaserin

Answer 4

serotonin receptor agonist

Question 5

bupropion/naltrexone

Answer 5

antidepressant/opioid antagonist combo

Question 6

Liraglutide

Answer 6

GLP-1 agonist

Question 7

treatment for severe binge eating disorder

Answer 7

lisdexamfetamine (vyvanse)

a modified amphetamine medication primarily indicated for the treatment of ADHD.

Question 8

overweight BMI ? obese? candiate for surgery

Answer 8

• BMI between 25 and 29.9 kg/m2 are considered overweight; BMI> 30 considered obese; BMI > 40 is a candidate for surgery..

Question 9

what are problems with pharm agents for weight loss

Answer 9

• Some drugs have received FDA approval for weight loss, but adherence is poor, adverse effects are common, and patients usually regain the lost weight when the drug is stopped.

Question 10

by doing what with diet, how can pt’s lose weight

Answer 10

• Adults can lose 1-2 lbs per week by consuming 500-1000 fewer calories per day.
• Several recent clinical trials comparing diets with the same degree of caloric restriction but composed of differing macronutrient composition, i.e., differences in protein, fat, carbohydrates, showed no significant differences in weight loss.
• Diets with low-fat versus low-carbohydrate content resulted in no differences in fat mass or lean mass at 6 months and no difference in amount of weight loss at 12 months (15-20 lbs).
• Patients on a diet can lose 5% of their body weight over the first 6 months, but over 2-3 years often return to baseline.

Question 11

what helps besides dieting alone lose weight

Answer 11

life coach

Question 12

pharm for obesity should be conserved for what pt’s

Answer 12

• Pharmacotherapy should be reserved for patients with a BMI>30 or BMI>27 with a weight-related comorbidity such as hypertension, dyslipidemia, or diabetes.

Question 13

sympathomimetic amines

MOA?
use?
how long can you use them?

Answer 13

• Sympathomimetic amines (mimic sympathetic nervous system agonists) are mostly structurally and functionally related to amphetamines. They work by releasing NE or preventing its neuronal reuptake. [Think methamphetamine].
• These drugs suppress appetite.
• These drugs are only approved for short-term use (weeks).

Question 14

ADR’s of sympathomimetic amines

Answer 14

• All of these drugs are controlled substances and must be prescribed carefully.
• All these drugs can increase heart rate, raise blood pressure, and cause nervousness and insomnia.

Question 15

phentermine /topiramate ER (Qysmia)

MOA

should we be using this drug?

Answer 15

sympathomimetic amine/antiepileptic combo

• Phentermine is a sympathomimetic amine and topiramate (Topamax) is used to treat epilepsy and migraine. Phentermine is FDA-approved for short-term treatment of obesity. Topiramate was observed in clinical trials (unrelated to obesity) to cause significant weight loss. The combination was recently (2013) FDA-approved for treatment of obesity.

schedule IV

• In clinical trials, Qsymia was effective in producing dose-dependent weight loss (6-13 kg over 56 weeks). It also was effective in maintaining weight loss over 2 years.

• This is arguably the most efficacious weight loss drug studied so far. But do the math! The best clinical trial results for this drug report that 66.7% of patients achieved > 5% weight loss after 56 weeks of treatment at the highest dose. Average beginning baseline weight was 118 kg (~260 lbs). So, 5% of 260 lbs is 13 lbs. Average weight loss on the drug was 12.6 kg (~28 lbs). Conclusion: the average patient went from 260 lbs to 232 lbs. That is significantly better than placebo (1.9 kg weight loss; 17.3% of patients > 5% weight loss), but is it a sufficient clinical endpoint?
• Qsymia has troublesome side effects. The discontinuation rate during the trials was about 40%. Qsymia is contraindicated during pregnancy and is available only through a restricted access program designed to prevent fetal exposure to the drug.

Question 16

when should you discontinue use of Qsymia and how should you do this

Answer 16

• If >5% weight loss is not achieved after 12 weeks at maximum dose, the drug should be gradually discontinued; abrupt discontinuation of topiramate can cause seizures even in patients with no history of epilepsy.

Question 17

ADR’s of Phentermine/Topiramate ER (Qsymia)

Answer 17

• Adverse effects include dry mouth, paresthesia, constipation, weird taste, and insomnia. This drug is contraindicated for use during pregnancy.

Question 18

Orlistat (Xenical, Alli)

Answer 18

lipase inhibitor

• It is a pancreatic and gastric lipase inhibitor that decreases the absorption of fat from the GI tract.
• Used as an adjunct to diet, it is modestly effective in increasing weight loss (about 3kg more than patients taking placebo).

Question 19

ADR’s of Orlistat

Answer 19

• Adverse effects of Orlistat limit its use. Flatulence with discharge, oily spotting, and fecal urgency occur predominantly after high-fat indiscretions and are associated with a high incidence of drug discontinuation.

CI in pregnancy

Question 20

Lorcaserin (belvig)

Answer 20

Serotonin receptor agonist

• Lorcaserin is a new drug (2013); it is a selective serotonin 2C agonist that suppresses appetite.
• It is a schedule IV controlled substance; it is only modestly effective for weight loss, but is generally well tolerated.
• About 50% of patients taking the drug in clinical trials lost > 5% of their initial body weight; the average placebo-corrected weight loss after 1 year of use has been 3 kg (6.6 lbs). Patients who continued on lorcaserin regained about 25% of their initial weight loss in the second year.

Question 21

when should you stop taking lorcaserin

Answer 21

• Patients that fail to lose > 5% of their baseline weight by 12 weeks should stop taking lorcaserin.

Question 22

ADR’s of lorcaserin

Answer 22

• Adverse effects of lorcaserin include headache, nausea, and dizziness. Drug discontinuation during clinical trials was about 35-50%. Lorcaserin is contraindicated for use during pregnancy and should not be administered to patients also taking MAO inhibitors, SSRIs, or SNRIs ***

Question 23

Bupropion/naltrexone (Contrave)

Answer 23

Antidepressant/Opioid Antagonist Combination

Bupropion is an appetite suppressant

Naltrexone opioid receptor antagonist

• The combination of bupropion + naltrexone (Contrave) has recently (2014) been approved for weight loss. It is not a controlled substance.
• Bupropion is an appetite suppressant and naltrexone potentiates that effect.
• In four clinical trials Contrave was associated with > 5% weight loss in 39-66% of patients after 56 weeks. Placebo-corrected weight loss at the end of 56 weeks was 4-5 kg (8.8 -11 lbs).
• If weight loss of > 5% is not achieved after 12 weeks, the drug should gradually be discontinued.

Question 24

ADR’s of bupropion/naltrexone (Contrave)

Answer 24

• Adverse Effects: include nausea (the major reason for discontinuation) vomiting; headache, constipation, dizziness, and dry mouth.

Serious neuropsychiatric reactions have been reported with the use of bupropion for smoking cessation.

Other adverse effects have been reported. Use of Contrave during pregnancy is contraindicated.

Question 25

Liraglutide (saxenda)

Answer 25

GLP-1 agonist

• Liraglutide is an injectable, glucagon-like peptide-1 (GLP-1) agonist used to treat type 2 diabetes as Victoza.
• A single clinical trial in obese adults without diabetes found that after 1 year patients treated with Liraglutide lost 5.8 kg more than patients with placebo.`

Question 26

ADR’s of liraglutide

Answer 26

• Adverse effects of Liraglutide include nausea, vomiting, constipation, and diarrhea. Liraglutide slows gastric emptying and may decrease the rate and extent of absorption of other drugs. FDA has required a boxed warning about the risk of thyroid C-cell tumors. Saxenda is contraindicated for use during pregnancy.

Question 27

weight loss effects on insulin

Answer 27

• Weight loss increases insulin sensitivity and may increase the risk of hypoglycemia in patients with diabetes taking glucose-lowering drugs.

Question 28

• Clinical trials of weight loss drugs used to treat overweight or obese type 2 diabetes patients have found that:
o Orlistat ….

Answer 28

treatment for 6-12 months resulted in an additional 0.4% reduction in HbA1c.

Question 29

Clinical trials of weight loss drugs used to treat overweight or obese type 2 diabetes patients have found that:o Phentermine/topiramate ER ….

Answer 29

produced an additional 6.7% weight loss and 0.4% reduction in HbA1c compared to placebo.

Question 30

lorcaserin effects on HbA1c

Answer 30

o Lorcaserin produced a decrease in HbA1c of 0.5-0.6% in type 2 diabetes patients being treated with metformin, a sulfonylurea, or both.

Question 31

effects of bupropion/naltrexone on HbA1c

Answer 31

o Bupropion/naltrexone produced an additional 3.2% weight loss and 0.5% reduction in HbA1c compared to placebo.

Question 32

SSRi’s and weight loss?

Answer 32

• SSRI antidepressants may induce weight loss in the short term, but long-term use can lead to weight gain. They are not recommended for weight loss.

Question 33

metformin for weight loss?

Answer 33

• Metformin (Glucophage) produces modest weight loss, rather than weight gain like the sulfonylureas. Patients adhering to a metformin treatment plan for up to nine years showed significant and sustained weight loss.

Question 34

adjustable gastric banding

Answer 34

a restrictive procedure with no associated malabsorption – loss of “excess weight” over BMI of 25 was 47% over > 10 years.

less weight loss than sleeve or roux-en-y

safer with lower mortality rates

Question 35

sleeve gastrectomy

Answer 35

o a laparoscopic partial gastrectomy –loss of “excess weight” was 59% over > 5 years.

Question 36

roux-en-Y gastric bypass

Answer 36

is a mixed restrictive and malabsorptive procedure that involves creation of a proximal pouch of stomach and anastomoses it to a limb of jejunum, bypassing most of the stomach, all of the duodenum, and the first 15-20 cm of the jejunum. The procedure results in an “excess weight” loss of 66% after 2 years. Adverse effects of this procedure can be significant.

• Studies showed that gastric bypass led to remission rates of 67% for type 2 diabetes, 38% for hypertension, and 60% for dyslipidemia compared to 29%, 17%, and 23% with gastric banding studies. Significant reductions in all-cause and cardiovascular mortality in surgically treated patients compared to obese controls have been shown through meta-analysis of data from 8 large clinical trials.

Question 37

Vyvanse

Answer 37

Lisdexamfetamine

• Lisdexamfetamine was approved (Jan. 2015) for the treatment of moderate to severe binge eating disorder (B.E.D.) in adults. B.E.D. is the most common adult eating disorder in the U.S.
• The FDA approved the drug for this indication after two clinical trials (N=350, 375) showed decreases in binge eating days per week (4.79 at baseline to 0.78 at week 12) compared to placebo (4.60 to 2.22). Improvement in other scales of behavior was also demonstrated.
• Adverse effects of lisdexamfetamine include dry mouth, insomnia, decreased appetite, constipation, felling jittery, and anxiety; i.e., typical amphetamine side effects.