obesity

statistics

high prevalence in adults: 41.9% (2017-2021)

^ even in ages 2-19: 19.7% (2017-2020)

excess wt associated w/ increased morbidity + mortality, decreased qol, increased healthcare costs

college degree → lower obesity prevalence

non-hispanic black adults» hispanic adults > non-hispanic white adults > non-hispanic asian adults

low SES → childhood obesity

highest prevelance in south us

pathophys: receptor/NT systems involved

serotonin (5-HT), norepinephrine, dopamine, glucagon-like peptide-1 (GLP-1), ghrelin, alpha- melanocyte-stimulating hormone, neuropeptide Y, orexin

etiology

increased energy storage resulting from an imbalance btwn energy intake + expenditure over time

influences: genetics, environmental factors (diet, exercise, proximity to others w/ obesity, SES), med conditions, medications

medical conditions associated w/ obesity

cushing’s disease, growth hormone deficiency, insulinoma, leptin deficiency, hypothyroidism, psychiatric disorders (binge eating disorder, schizophrenia), genetic syndromes (prader-willi, bardet biedly, wilson-turner syndrome)

meds that cause medication induced wt gain

atypical antipsychotics (olanzapine, clozapine, quetiapine)

antiepileptics (valproic acid derivatives, carbamazepine, gabapentin/pregabalin)

antidepressants (not all; mirtazapine, tricyclic antidepressants

corticosteroids, hormones, insulin/thiazolidinediones/sulfonylureas, beta blockers

obesity class I BMI

30-34.9 kg/m²

obesity class II BMI

35-39.9 kg/m²

obesity class III BMI

≥40kg/m²

what weight related complications can pts experience

CVD/CVD mortality

T2DM, prediabetes

HTN

non-alc fatty liver disease/ non alc steatohepatitis

PCOS

female infertility

male hypogonadism

asthma

OSA

osteoarthrtis

GERD

certain cancers

nonpharm therapy

increased physical activity, dietary modification, bariatric surgery

main types of bariatric surgery

roux-en-Y gastric bypass (RYBG)

sleeve gastrectomy

laparosropic adjustable gastric banding

other procedures that havent achieved success

intragastric balloon therapy

vagal blockade

aspiration

implantable medical devices used in adjunct to diet and exercise

gastric emptying systems (aspireassist)

electrical simulation systems (maestro rechargable system)

gastric balloon systems (orbera intragastric balloon, the reshape integrated dual balloon system, obalon balloon system)

nonsystemic oral superabsorbent hydrogel (plenity)

targets of pharmacologic therapy

peripheral tissues → block intestinal lipases, decrease fat absorption

CNS → modulate NTs, suppress food intake

who should be considered for pharmacotherapy

adults: BMI≥ 30 kg/m², BMI ≥27 kg/m² w/ obesity related complications

children/teens: age >12y w/ BMI > 30kg/m², wt ≥95 percentile for age

fda approved agents that work on the periphery

orlistat, GLP-1 agonist (liraglutide, semaglutide, tirzepatide, orforglipron)

fda approved agents that work on the CNS

sympathomimetics, phentermine/topiramate, naltrexone/bupropion, olanzapine/samidorphan, setmelanotide

what is used off label for obesity

metformin, topiramate, lisdexamfetamine (approved for binge eating disorder)

orlistat OTC brand name

alli

orlistat rx brand name

xenical

dosing for alli (orlistat)

60mg po tid

dosing for xenical (orlistat)

180 mg po tid

when is it best to take orlistat

w/in 1h of fatty meal

contraindications of orlistat

cholestasis, chronic malabsorption syndrome, pregnancy

adrs for orlistat

gi effects (abd pain, fatty/oily stools, fecal incontinence)

severe liver injury

what do you monitor for efficacy for orlistat

wt loss

counseling points for orilstat

take 1h before or after fat-containing meals

may require fat-soluble vitamin supplementation, separate by 2h from orlistat dose (vit ADEK)

sig interaction w/ cyclosporine → decreases cyclo concentrations, separate by 3h

separate from levothyroxine by 4h

GLP-1 agonist moa

delays gastric emptying, increase satiety through GLP-1 receptor binding in the brain → increases insulin secretion, reduces glucagon secretion

which glp-1s are approved for tx of obesity

liraglutide, semaglutide, tirzepetide, orforglipron

brand name of liraglutide

saxenda (victoza)

dosing of liraglutide

starting 0.6 mg qd and titrate to 3mg sq qd

semaglutide brand names

wegovy (PO, SQ), ozempic (SQ)

dosing for semaglutide

0.25 mg once weekly, escalate monthly to 2.4 mg sq once weekly

tirzepatide brand names

zepbound (mounjaro)

dose of tirzepatide

starting: 2.5 mg sq weekly, titrate up to 15 mg sq once weekly

injection site for liraglutide, semaglutide, tirzepatide

abdomen, thigh, upper arm

orforglipron brand name

foundayo

dosing for orforglipron

0.8 mg PO once daily, titrate every 30 d up to a target of 17.2mg once daily

black box warnings for glp-1 agonists

risk of thyroid C-cell tumors/contraindicated in persons w/ or fam hx of multiple endocrine neoplasia syndrome

warnings/precautions for glp-1 agonists

acute pancreatitis, gall bladder disease, hypoglycemia, acute kidney injury

adverse effects of glp-1 agonists

gi upset (>10%): diarrhea, nausea, vomiting, constipation, abd pain, dyspepsia

hypoglycemia

inj site rxns

monitoring of glp-1 agonists

efficacy (wt loss/a1c if comorbid DM) - d/c liraglutide if 4% wt loss not achieved at 16 wks

HR

renal fxn (scr/BUN)

worsening of diabetic neuropathy (if comorbid T2DM)

adverse effects: gi sxs, s/sx of pancreatitis (lipase)

admin of glp-1 agonists

need pen needles, alc swabs, gauze/cotton balls, sharps container

make sure to rotate inj sites!!!

counseling points for glp-1 agonists

med admin, storage, disposal

store in fridge!

adverse effects

expectations regarding efficacy (ex. liraglutide: lose 4% of body wt w/in 16 wks)

exercise, diet

moa of sympathomimetics

appetite suppression through monoamine modulation

sympathomimetic agents

phentermine, benzphetamine, diethylpropion, phendimetrazine

can sympathomimetics be used long term?

short term (≤3 mon) or intermittent use is recommended

schedule of sympathomimetics

schedule III/IV controlled substances

which sympathomimetic is not approved for ages >16

benzphetamine, phendimetrazine >17y

important points for sympathomimetics

carry risk of dependence, larger percent wt loss compared to long-term agents, may elevate hr/bp

brand names of phentermine

adipex, adipex-P, lomaira

dosing for adipex

15-30 mg once daily w/in 2 h of breakfast

dosing of adipex-P

37.5 mg PO once daily in the morning w/ or w/o food

dosing of lomaira

8 mg po tid 30 mins before meals

which schedule is phentermine

schedule III

brand name of benzphetamine

didrex

which schedule is benzphetamine

schedule IV

dosing for didrex

25-50 mg po once daily in the morning, may titrate to TID as tolerated

brand names of diethylpropion

tennuate (IR), tennuate dospan(XR)

which schedule is diethylpropion

schedule IV

dosing for diethylpropion IR

25 mg po tid, 1h before meals

dosing for diethylpropion XR

75 mg PO once daily in the midmorning

which schedule is phendimetrazine

schedule III

brand name of phendimetrazine

bontril

what formulations does phendimetrazine come in

IR tablet, capsule XR

dosing for phendimetrazine IR

35 mg po bid-tid 1h before meals, max 70 mg po tid

dosing for phendimetrazine XR

105 mg po once daily 30-60min before morning meal

contraindications of sympathomimetics

cardiovascular disease, severe HTN, hyperthyroidism, glaucoma, hx of substance abuse, MAOI use, pregnancy

adverse effects of sympathomimetcis

bp/hr increase, palpitations, dizziness, insomnia, xerostomia, flushing/sweating

what to monitor for sympathomimetics

efficacy: wt loss

adverse effects: bp/hr, anxiety, sleep

tachyphylaxis

counseling points of sympathomimetics

wt loss will occur in the short-term

not for continuous, long term use, tolerance can develop

admin info: most taken in the morning to help with insomnia

dont admin w/ MAOI!! → risk of hypertensive crisis, 2 wk washout period required

notify physician if experiencing abnormal heart palpitations

cns acting agents used for obesity

phentermine-topiramate

bupropion-naltrexone SR

olanzapine samidorphan

setmelanotide

phentermine/topiramate brand name

qsymia

phentermine/topiramate moa

altered noradrenergic neurotransmission + altered gaba and noradrenergic neurotransmission → wt loss

why is longer term use of phentermine-topiramate ok

since its a combo drug, there are lower doses of each drug than when used as monotherapy

what age is phentermine-topiramate approved for

age >12

dosing range for phentermine-topiramate

3.75mg/23mg - 15mg/92mg

how often should pts take phentermine-topiramate

once daily in the morning

contraindications of phentermine-topiramate

pregnancy category X

hyperthyroidism

concomitant use of MAOIs or w/in 14 days of discontinuation

glaucoma

warnings/precautions of phentermine-topiramate

hr increases, depression/suicidality, mood/sleep sx, angle closure glaucoma, metabolic acidosis, decreased renal fxn, skin rxns, cognitive impairment, substance use hx

drug interactions for phentermine-topiramate

non k+ sparring diuretics → hypokalemia

alcohol → may potentiate effects

adverse effects of phentermine-topiramate

dizziness (phe)

headache (phe)

xerostomia (phe)

memory + concentration impairment (top)

paresthesias (top)

nephrolithiasis (top)

constipation (phe/top)

monitoring parameters of phentermine-topiramate

efficacy: wt loss

sleep (phe)

bp/hr (phe)

anxiety (phe)

electrolytes (hypokalemia, decreased serum bicarb) (top)

scr/BUN (increases) (top)

mood (top)

abrupt withdrawal - seizures (top)

is a med guide required when dispensing phentermine-topiramate

yes!

counseling points for phentermine-topiramate

use effective contraception → embryofetal toxicity (women), call MD if spotting occurs on combined ocp

REMS programs requirements - pregnancy test required for rx, dispense w/ med guide

risk of seizure w/ abrupt withdrawal

avoid excessive alc use

bupropion-naltrexone SR brand name

contrave

bupropion-naltrexone SR dosing range

8mg/90mg - 32mg/360mg po BID

moderate hepatic/renal impairment: max dose 8mg/90mg po bid

hepatic/ERSD impairment: not recommended

contraindications of bupropion-naltrexone SR

seizure disorders (bup)

abrupt discontinuation of benzos, alc, antiepileptics (bup)

bulimia/anorexia nervosa (bup)

uncontrolled htn (bup)

concomitant use of MAOIs, linezolid, iv methylene blue w/in 14d of discontinuation (bup)

concomitant opioid, opioid agonist/partial agonist use, acute opioid withdrawal (ntx)

warning/precautions of bupropion/naltrexone SR

hr/bp increases (bup)

depression/suicidality w/ age <24 (bup)

angle closure glaucoma (bup)

hepatotoxicity (ntx)

black box warning for bupropion-naltrexone SR

risk of suicidal thoughts and behavior in those < 24 yo

drug interactions/ PK for bupropion-naltrexone SR

bupropion-moderate 2d6 inhibitor and 2b6 substrate

• may increase concentrations of 2d6 metabolized drugs

• 2b6 inhibitors (clopidogrel/ticlopidine) can increase (bup)

• 2b6 inducers can increase (bup)

MAOIs- increased risk of hypertensive crisis

caution w/ dopaminergic drugs

false + urine tox screen (bup)

dont coadmin w/ opioid derivatives!

adverse effects of bupropion- naltrexone SR

gi upset (constipation/diarrhea/nausea), insomnia, anxiety, sweating/hot flashes, xerostomia, HA, elevated hr/bp

monitoring parameters for bupropion-naltrexone

wt loss - d/c if minimal loss after 3 mon

renal fxn (scr)

hepatic fxn (alt/ast)

hr/bp

worsening of suicidal thoughts/depression

psychiatric adverse effects (sleep, mood, mania, psychosis)

is a med guide required when dispensing bupropion-naltrexone SR

yes!

counseling points for bupropion-naltrexone SR

d/c if ≥5% wt loss not achieved at 12 wks

educate on potential ddis (opioid derivatives!!)

adverse effects: difficulty sleeping, neuropsychiatric sx (eps if age 18-24)

olanzapine/samidorphan brand name

lybalvi

olanzapine/samidorphan moa + indication

atypical antipsychotic formulated w/ opioid antagonist (samidorphan)

indication: schizophrenia/bipolar disorder to prevent antipsychotic induced wt gain

reduces wt gain associated w/ olanzapine

setmelanotide brand name

imcivree

setmelanotide indication

chronic wt management in adults and children > 6 yo w/ generally confirmed or suspected proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency + bardet-biedl syndrome

testing for variants is required

setmelanotide moa

melanocortin 4 (MC4) receptor agonist-analog of endogenous alpha-melanocyte stimulating hormone (alpha-MSH)