Anti-obesity medications

absolute CI for phentermine

Cardiac disease (CAD, stroke, arrhythmias, heart failure, uncontrolled hypertension) glaucoma, hyperthyroidism, substance abuse, psychosis, pregnancy

medication considerations for phentermine:

MAOIs (Level 1 DDI – CI, HTN Crisis), Antihypertensive or Caffeine, (↑HR, BP), Bupropion (↑Seizure Risk) Antidiabetics (↑Glucose), Geriatric (Start low dose)

renal adjustments for phentermine

eGFR 15-29 = Max of 15 mg/day

avoid if < 15

MOA of phentermine

increases release and inhibits reuptake of NE (lesser extent dopamine) and thereby stimulates POMC neurons to suppress appetite

dosing of phentermine

15–37.5 mg: Q.D or in divided doses (15, 18.75,
37.5 mg)
Lomaira (2016) = 8 mg T.I.D, 30 minutes before
meals

total body weight loss vs placebo for phentermine

poor evidence base, rapid tolerance develops (8-12 weeks) and weight regain

liver adjustments for phentermine

no dosage adjustments necessary

indication for phentermine

BMI >30 or 27 w/comorb. Short-term (few weeks), Age >17

what does the AACE/ACE say about phentermine?

has not been shown to produce long-term weight or health benefits and cannot generally recommend

timing of phentermine admin

avoid evening administration - stimulant can cause insomnia

dose escalation for phentermine

use lowest dose possible, especially HTN, DM, geriatrics

what to monitor on phentermine

BP, HR, glucose in diabetics

cost of phentermine

can be as low as $20/mo

CI for orlistat

pregnancy, malabsorption, cholestasis, oxalate kidney stones

precautions for orlistat

severe liver disease, choleslithiasis, fat soluble vitamin deficiency

medication considerations for orlistat

Warfarin (↑ effect), anti-seizure (↓ effect), levothyroxine (↓ effect), cyclosporine (↓ effect)

renal adjustments for orlistat

none

liver adjustments for orlistat

avoid in severe liver disease

MOA of orlistat

bind gastric and pancreatic lipases in lumen of the stomach and small intestine and thereby reduces fat absorption into the body

dosing of orlistat

OTC = 60 mg PO TID

Rx = 120 mg PO TID

total body weight loss vs placebo in orlistat

1-year: -4%

4-year: -2.6%

indication for orlistat

BMI > 30 or 27 with comorbidities, chronic >/= 12 years old

side effects of orlistat

fatty stools, fecal urgency or incontinence, oily spotting, abdominal pain (increase with >30% kcal from fat)

what is true regarding the discontinuation of orlistat?

rate is high due to side effects

CI for Qsymia

pregnancy, breastfeeding

precautions for Qsymia

alcohol use (worsen cognitive side effects)

medication considerations for Qsymia

phentermine profile, hypokalemia, CNS depressants

renal adjustments for Qsymia

CrCl < 50 mL/min = max 7.5/46 mg (avoid < 30)

liver adjustments for Qsymia

Child Pugh B = max 7.5/46 mg (avoid in C)

MOA of Qsymia

Topiramate: Inhibits NPY/AgRP synaptic release of GABA that plays a role in Inhibiting POMC Neurons. Inhibiting the release of GABA reduces the suppression of POMC neurons and thereby increases Appetite Suppression.

dosing for Qsymia

Starter (Titration): 3.75 / 23 mg x 2-weeks

Recommended (Treatment): 7.5/46 mg or 15/92 mg

Escalation (Titration): 11.25/69 mg

High Dose (Treatment): 15/92 mg

total body weight loss vs placebo for Qsymia

1-year: -8.6% (high dose), 6.6% (treatment dose)

2-year: -8.7% (high dose), 7.5% (treatment dose)

Indication for Qsymia

BMI > 30 or > 27 with comorbidities, chronic, age > 18 (16 years old is off label)

dynamic dosing schedule for Qsymia

Starter to Treatment Dose, evaluate:

Not at 3% weight loss after 12-weeks on Treatment Dose: Stop or escalate to 11.25/69 x 14d —→15/92 mg

Not at 5% after 12-weeks on High dose = Stop! Every other day x 1-week to avoid seizures 

side effects of Qsymia

paresthesia, concentration/memory loss, depression, low bicarb

which anti-obesity medication was voluntarily withdrawn from the US market due to increased rates of cancer diagnoses?

Belviq (Lorcaserin)

CI for Contrave

Pregnancy, breastfeeding, uncontrolled HTN, seizure disorder, anorexia/bulimia, severe depression, MAOI, chronic opiate use, acute opiate need, drug or alcohol withdrawal 

Precautions for Contrave

Cardiac arrhythmias, glaucoma, migraines, anxiety, bipolar disorder, seizure (bupropion lowers threshold)

medication considerations for Contrave

MAOI, Pimozide, Thioridazine, SSRI

renal adjustments for Contrave

CrCl 30-49 = Max 8/90 B.I.D (Avoid <30)

liver adjustments for Contrave

Child Pugh B = Max 8/90 BID (avoid C)

MOA for Contrave

Bupropion: Increases the release and inhibits the reuptake of Dopamine (and to lesser extent Norepinephrine) thereby STIMULATING POMC NEURONS to SUPPRESS APPETITE

Naltrexone: Opiate receptor blockade prevents β-endorphin binding that tonically inhibits POMC Neurons. Reduction of Dopamine in reward centers influences desires, palatability

Dosing for Contrave

Only supplied as an 8/90 tablet

•Week 1: 8 (Naltrexone)/90 (Bupropion) once a day in a.m.

•Week 2: 8/90 mg twice a day 

•Week 3:  16/180 mg a.m. + 8/90 mg p.m. 

•Week 4: 16/180 mg a.m. + 16/180 mg p.m.

total body weight loss vs placebo for Contrave

1 year: -4.2%

No data available beyond 1 year

indication for Contrave

BMI > 30 or 27 with comorbidities, chronic, age > 18

evaluation of efficacy for Contrave

if not >5% weight loss at week 16 —→ stop med

side effects of Contrave

generally mild, N/V, HA, dizzy, dry mouth

how long should patients be opiate free for before starting Contrave?

7-10 days

monitoring for Contrave

HR, BP, depression, suicidal ideation, migraine, hypoglycemia with insulin or secretagogue, seizures, LFT’s

what is true regarding labs and patients on Contrave?

may cause false positives for amphetamines

contraindications for Saxenda

pregnancy, breastfeeding, MEN2, pancreatitis, medullary thyroid cancer, acute gall bladder

precautions for Saxenda

pancreatitis history, gastroparesis, gall stones, dehydration

major DDI with Saxenda

none (modestly lowers BP and glucose)

renal and liver adjustments for Saxenda

none

MOA of Saxenda

Stimulates POMC NEURONS to SUPPRESS APPETITE. Decreases GASTRIC EMPYTING thereby stimulating VAGAL AFFERENTS for MEAL TERMINATION

dosing of Saxenda

Subcutaneous Injection - Daily

•Week 1:   0.6 mg once a day

•Week 2-5:   0.6 mg weekly increase to reach 3 mg

total body weight loss vs placebo for Saxenda

1 year: -5.6%

No data available beyond 1-year

indication for Saxenda

BMI > 30 or 27 with comorbidities, chronic

age for Saxenda

adult dosing,12-17 year-old dosing, 7-11 year-old dosing (off-label)

evaluation of efficacy of Saxenda

not > 4% weight at week 16 —→ Stop

side effects of Saxenda

N/V (may cause dehydration), constipation, diarrhea, indigestion, increased heart rate, gall stones, hypoglycemia (with insulin or secretagogue only)

monitor for Saxenda

pancreatitis, improving glucose (T2DM approved)

CI for semaglutide

Pregnancy, breast feeding, MEN2, pancreatitis, medullary thyroid cancer, acute gall bladder

precautions for semaglutide

pancreatitis history, gastroparesis, gall stones, dehydration

major DDI for semaglutide

none

renal and liver adjustments for semaglutide

none

MOA for semaglutide

Stimulates POMC NEURONS to SUPPRESS APPETITE

Decreases GASTRIC EMPYTING thereby stimulating VAGAL AFFERENTS for MEAL TERMINATION

dosing for semaglutide

Subcutaneous Injection - weekly

Week 1-4:  0.25 mg once a week

Monthly:     Increase 0.25 mg to reach 2.4 mg at week 16

total body weight loss vs placebo for semaglutide

1 year: -12.4% (more than twice that seen with Saxenda)

indication for semaglutide

BMI > 30 or 27 with comorbidities, chronic.

age for semaglutide

adult dosing,12-17 year-old dosing, 7-11 year-old dosing (off-label)

evaluation of efficacy for semaglutide

monthly for proper titration

side effects of semaglutide

N/V (may cause dehydration), constipation, diarrhea, indigestion, increased heart rate, gall stones, hypoglycemia (with insulin or secretagogue only)

monitoring for semaglutide

pancreatitis, N/V, improving glucose (T2DM med)

contraindications for Zepbound

MTC, MEN2, active pancreatitis, acute gallbladder

precautions for Zepbound

History of Pancreatitis, Gallbladder Disease, IBD, UC, Crohns, Gastroparesis, Hypogylcemia (w/ insulin or sulfonylurea) Dehydration Risk (N/V), AKI History, Pregnancy, Breast feeding

major DDI for Zepbound

none (modestly lowers BP and glucose)

renal and liver adjustments for Zepbound

none

MOA for Zepbound

Stimulates POMC NEURONS to SUPPRESS APPETITE

Decreases GASTRIC EMPYTING thereby stimulating VAGAL AFFERENTS for MEAL TERMINATION

dosing for Zepbound

Subcutaneous Injection, Weekly

Week 1-4:  2.5 mg once a week

Monthly:     Increase by 2.5 mg/week up to a max of 15 mg

total body weight loss vs placebo for Zepbound

1 year: -20.9% (dose dependent)

indication for Zepbound

only FDA approved T2DM

age for Zepbound

adult only dosing recommendations

evaluation of efficacy for Zepbound

monthly for proper titration

side effects of Zepbound

N/V (may cause dehydration), constipation, diarrhea, indigestion, increased heart rate, gall stones, hypoglycemia (with insulin or secretagogue only)

monitoring for Zepbound

N/V, pancreatitis, improving glucose (T2DM Med)