obesity pharmacotherapy

byrd

what factors can contribute to obesity

genetics, epigenetics, culture (environment/behavior)

what is the number one risk factor of premature death and disability in the US

diet

what is the diagnostic criteria for binge-eating disorder

• frequent episodes of consuming large amounts of food more than once a week for > 3 months

• no self-induced vomiting or extra exercise

• eating attitudes test

what type of therapy is a beneficial treatment for binge-eating disorder

cognitive behavioral therapy

what is the only drug with an FDA indication for binge-eating disorder

lisdexamfetamine dimesylate

what drugs are not indicated for binge-eating disorder but may be beneficial off-label

some SSRIs

topiramate

GLP-1 agonists

what is the diagnostic criteria for night-eating syndrome

• at least 25% of daily consumption is consumed after evening meal

  • often greater than 50% of daily consumption

• recurrent awakenings from sleep that requires eating to go back to sleep

• morning anorexia

what is the treatment for night-eating syndrome

behavioral therapy — nutritional timing and content

what criteria of a disease does obesity meet

• impairment of normal functioning

  • appetite dysregulation, abnormal energy balance, endocrine/immune dysfunction

• S/S

  • increased body fat, joint pain, altered metabolism, sleep apnea

• harm/morbidity

  • T2DM, CV disease, cancer, osteoporosis, PCOS, MASLD, etc.

what are the subsets of obesity

sick fat disease (adipose tissue dysfunction) — metabolic dysfunction

fat mass disease — biomechanical/structural dysfunction

what can happen in adipose tissue dysfunction (adiposopathy)

elevated BG, elevated BP, dyslipidemia, other metabolic diseases

what can happen in fat mass disease

stress on weight-bearing joints, immobility, tissue compression, tissue friction

VAT fat vs. SCAT fat

VAT — abdominal fat, surrounds organs, acts as an endocrine organ

SCAT — fat found all over the body

what are some metabolic manifestations of adiposopathy

hyperglycemia, hypertension, hyperlipidemia, fatty liver, CKD, etc.

what are gender-specific manifestations of adiposopathy for women

hyperandrogenemia, hirsutism, acne, PCOS, menstrual disorders/infertility, gestational diabetes, etc.

what are gender-specific manifestations of adiposopathy in men

hypoandrogenemia, hyperestrogenemia, ED, infertility

what BMI is pre-obesity or overweight

>25 to <30

what BMI is obesity

>30

what is the risk of a BMI >25

elevated risk of CV disease

why is BMI unreliable when evaluating individual risk

does not take into account muscle mass — can over or underestimate individual risk

what is a more accurate measure of central adiposity and subsequent risk for obesity-related health issues

waist circumference

what is waist circumference

measure in the area between the last rib and top of the iliac crest

what is the relationship of weight loss to visceral fat reduction

5-10% weight loss can reduce visceral fat by 30%

what amount of weight loss can produce clinically meaningful benefits

3-5% weight loss

what is a reasonable goal for weight loss for people with obesity

5-10% loss over 3-6 months (~1-2 lbs per week)

overview of treatment guidelines for obesity

physical activity + diet + behavioral therapy — for everyone

elevate to pharmacotherapy based on BMI

elevate to bariatric surgery based on BMI

what is the recommended physical activity for obesity treatmetn

150 minutes of moderately vigorous activity per week

what calorie deficit is recommended for obesity treatment

500-750 kcal/day

what is the recommended behavioral therapy regimen for obesity treatment

>14 months — self monitoring of diet, physical activity, weight, and problem-solving

when is someone with a BMI >27 indicated for pharmacotherapy for obesity

must have a co-morbidity (or stage 1-3 CKM)

what BMI is automatically indicated for pharmacotherapy

>30

what are the

>35 with co-morbidity

>40 (no co-morbidity)

what drug classes can induce weight gain

anticonvulsants, antidepressants, atypical antipsychotics

conventional antipsychotics, DM meds, hormones

what class is phentermine

sympathomimetic

what class is orlistat

pancreatic lipase inhibitor

what effect does orlistat have for obesity therapy

reduces fat absorption → fewer inbound calories

what class is phentermine/topiramate ER

sympathomimetic/anticonvulsant

what class is naltrexone/bupropion SR

opioid receptor antagonist/dopamine and norepi reuptake inhibitor

what class is setmelanotide

melanocortin 4 receptor agonist

what is the effect of all obesity pharmacotherapy meds except orlistat

reduction in appetite

what FDA approved pharmacotherapy for obesity has the best efficacy for weight loss

tirzepatide — 15-21%

which FDA approved pharmacotherapy for obesity has the lowest efficacy for weight loss

naltrexone/bupropion SR — 5.4%

when should pharmacotherapy for weight loss be discontinued

if weight loss of at least 5% is not achieved after 12 weeks of max dose therapy

when should liraglutide (victoza) therapy be discontinued

if weight loss of at least 4% is not achieved after 16 weeks of therapy

what drug is phentermine strucuturally similar to

amphetamine — risk for abuse/addiction

what length of therapy is phentermine indicated for

short-term (12 consecutive weeks) — because rate of weight loss is greatest in first few weeks and declines in following weeks

what are contraindications for phentermine

CV disease, glaucoma, hyperthyroidism, pregnancy/breastfeeding — bc stimulant

what are ADRs of phentermine

overstimulation, palpitations, insomnia, hypertension, tachycardia

what are ADRs of orlistat

gas with discharge, fecal urgency, fatty/oily stool, increased defecation, fecal incontinence — bc leaving fat in GI tract to get excreted

when should orlistat be dosed

within 1 hour of fatty meal

what may decrease orlistat side effects

<30% fat in diet (less fat, less in GI, less GI effects)

when should orlistat not be used

in patients with history of nephrolithiasis (kidney stones)

what is the OTC form of orlistat

alli — 60 mg capsule

what are some drug interactions with orlistat

levothyroxine, contraceptives, fat soluble meds, warfarin, cyclosporine

what are some fat soluble meds that should not be taken with orlistat

gabapentin, lamotrigine, valproic acid, amiodarone — bc decreasing absorption of these meds

what supplementation is necessary when taking orlistat

fat soluble vitamins (2 hours before or after taking orlistat)

what is phentermine/topiramate approved for

chronic weight management

remember reg phentermine is for short term therapy

why should phen/topiramate be tapered on initiation and discontinuation

seizure risk

what should be monitored on phen/topiramate therapy

metabolic acidosis, hypokalemia, increase in SCr

what is naltrexone/bupropion contraindicated in

seizure disorders, bulimia or anorexia, chronic opioid or opiate agonist use

what are ADRs of naltrexone/bupropion

N/V/D, constipation, headache, dizziness, insomnia, dry mouth

what is a notable interaction for naltrexone/bupropion

CYP2B6 inhibitors — clopidogrel, ticlopidine

what is the boxed warning for naltrexone/bupropion

suicidal ideation and neuropsychiatric symptoms

what hypothalamic neurons do GLP1s work on

POMC/CART → increase satiety

NPY/AgRB → decrease hunger

what is the max dose of saxenda (liraglutide)

3 mg

what are the low doses for wegovy (semaglutide)

1.7 or 2.4 mg

what is the max dose of wegovy (semaglutide)

7.2 mg

what are the dosages for PO wegovy (semaglutide)

1.5-9 mg and 25 mg

what is wegovy (semaglutide) FDA approved for

obesity + ASCVD and MASH (fatty liver)

how should PO wegovy (semaglutide) be taken

1. 30 min before a meal (pref. breakfast)

2. no more than 4oz of water

what is foundayo (orforglipron)

oral non-peptide GLP1 agonist

why can foundayo be taken with a meal but PO wegovy must be taken on an empty stomach

wegovy has SNAC bc of poor bioavailibility — needs to land on stomach lining

foundayo is not a peptide so does not need SNAC for absorption

what is the mean weight loss for foundayo

~10-12% — less effective than PO wegovy

what is the max dose of zepbound (tirzepatide)

15 mg

what is the mean weight loss for zepbound (tirzepatide)

15-21% — most effective GLP

what is a unique FDA indication for zepbound (tirzepatide)

obstructive sleep apnea

what are the approved indications for wegovy vs zepbound

weg — overweight/obesity, CV risk reduction and MASH

zep — overweight/obesity, sleep apnea

what age can wegovy be used in for weight reduction

12+ years

what age can zepbound be used in for weight reduction

18+ years

what is plenity

FDA approved device — first non-systemic oral capsule for weight management made of cellulose and citric acid

what patients are indicated for plenity

BMI 25-40

how do patients take plenity

3 caps 20 minutes before lunch and dinner with a bottle of water (16 oz)

how does plenity work

expands in the stomach to make you feel full

what does CKM stand for

cardiovascular-kidney-metabolic

what is stage 1 CKM characterized by

excess/dysfunctional adipose tissue (BMI >25 or prediabetic) without the presence of other metabolic risk factors or CKD

FBG >100 to 125 or A1c 5.7% to 6.4%

what is stage 2 CKM characterized by

metabolic risk factors, CKD, or both (T2DM, hypertrglyceridemia, hypertension, metabolic syndrome)

what is stage 3 CKM characterized by

subclinical CVD in CKM syndrome

what is stage 4 CKM characterized by

clinical CVD in CKM syndrome

what are the characteristics of metabolic syndrome

• 3 or more of the following

  • waist circum. >88 cm (women), >102 cm (men)

  • HDL <40 (men) and <50 (women)

  • triglycerides >150

  • HTN

  • FBG >10

what is first line for CKM stage 1 (BMI >25 with no co-morbidities)

lifestyle intervention + GLP-1 (if BMI >27)

what is second line therapy for CKM stage 1

non-GLP1 obesity pharmacotherapy

what intervention may be necessary for CKM stage 1-3 if there is no adequate weight loss with lifestyle interventions with or without pharmacotherapy

metabolic bariatric surgery

what medication may be efficacious in patients who have had bariatric surgery and regained a significant amount of weight

GLP1 therapy

what is first line therapy for patients with stage 4 CKM (BMI >27 + ASCVD)

lifestyle intervention + GLP1 with proven CV benefit

what is alternative therapy for patients with CKM stage 4 who have not reached weight loss goal with or without max pharmacotherapy

metabolic bariatric surgery

what pharmacotherapy should not be used in CKM stage 4

naltrexone/bupropion or phentermine-containing agents — can increase BP and heart rate, do not want that in someone with ASCVD

what calorie reduction will result in a loss of 1lb per week

500 kcal/day — 1200-1500 kcal/day total (women), 1500-1800 kcal/day total (men)

what calorie deficit requires medical supervision

<800-1000 kcal/day

what is the premise of a restricted-carb diet

lower insulin levels and burn fat for energy

what is the premise of the keto diet

severely limit carbs and emphasize fats → body goes into ketosis → body switches from glucose to fat for energy