Weight Loss and Obesity - Lewis

BMI / Weight category

visceral vs subcutaneous fat

• Visceral fat: fat surrounding organs

  • Considered more harmful

• Subcutaneous fat: fat under the skin

  • Considered less harmful, but can contribute to overall weight gain

metabolic syndrome: must contain 3 out of 5 out of following

• Fasting glucose: 100-125 mg/dL

• BP ≥ 135/80 OR receiving HTN trx

• Triglycerides > 150 mg/dL

• HDL

  • < 50 mg/dL for women

  • < 40 mg/dL for men

• Waist circumference

  • ≥ 35 inches for women

  • ≥ 40 inches for men

Meds associated with weight gain

• ASMs

  • CBZ, gabapentin, pregabalin

• Antidepressants

  • MAOIs, TCAs, paroxetine, citalopram, escitalopram, mirtazapine

• Antipsychotics

  • Clozapine, olanzapine, quetiapine, risperidone, haloperidol, aripiprazole

• Antiretrivirals

  • Protease inhibitors (-virs)

• Glucocorticoids

• Progestins

• DM medications

  • Insulin, sulfonylureas, meglitinides, thiazolidinediones

• Mood stabilizers

  • Lithium

other etiology of obesity

• Genetics

• environment

  • easily accessible food supply

  • reduction in physical activity

  • sedentary lifestyle

  • friends, family members

  • socioeconomic status

  • religious belief

  • gut microorganisms

  • lack of sleep

types of bariatric surgery

• adjustable gastric band

  • more restrictive than malaborptive

  • affect on absorption: minimal

• sleeve gastrectomy

  • restrictive, somewhat malaborptive

  • reduced gastric volume, increased gastric pH, accelerated gastric emptying

• roux-en-Y gastric bypass

  • restrictive, malabsorptive

  • reduced gastric volume, increased gastric pH, accelerated gastric emptying, decreased surface area for absorption, reduced 1st-pass metabolism, shorter intestinal transit time, more distal delivery of pancreatic secretions

surgery indications

• BMI ≥ 40

• BMI 35-39.9 + at least ONE comorbidity

affects of surgery on medications

• absorption

• distribution

• metabolism

• excretion

• Absorption

  • Increased gastric pH

  • Reduced bioavailability of ER meds → pH causes ER to dissolve too early

  • Shorter t_1/2

• Distribution

  • Reduced volume of distribution

• Metabolism

  • Potentially decreased CYP metabolism in the small intestine

• Excretion

  • Not likely to be affected, however, CrCl may be altered

surgery may lead to

• reduced vitamin and mineral absorption

• deficiencies

  • thiamine

  • copper zinc

• all needed supplementation usually accomplished w/ 2 chewable MVI each day

medication concerns post surgery:

• what formulations avoided?

• avoid drugs that increase risk of GI ulceration

• re-assess treatment for obesity-related disease

• formulations

  • enteric coated

  • delayed release

  • extended-release formulations

• medications avoided

  • DOACs

  • NSAIDs

  • corticosteroids

  • biphosphonates

• obesity-related diseases

  • HTN

  • dyslipidemia

  • diabetes

use — to reduce risk of GI ulcer post-surgery

PPIs (omeprazole)

when should medications be used for weight-loss?

• BMI ≥ 27 w/ ≥1 comorbidities

  • HTN

  • dyslipidemia

  • T2DM

  • obstructive sleep apnea

• BMI ≥ 30 w/o comorbidities

weight loss medications

• short term

• long term

• short term

  • Phentermine (Adipex)

• long term

  • Phentermine/Topiramate XR (Qsymia)

  • Naltrexone/Bupropion (Contrave)

  • Orlistat (Xenical; Alli)

  • Semaglutide (Wegovy) - GLP1 agonist

  • Orforglipron (Foundayo) - GLP1 agonist

  • Tirzepatide (Zepbound) - dual mechanism GLP-1 and GIP

all drugs for weight loss maintenance:

• CI or avoided in

• adjunt to

• d/c if

• CI or avoided in

  • pregnancy / breastfeeding

• adjunct to

  • reduced-calorie diet and increased physical activity

• d/c if

  • weight loss ≥ 5% is not achieved within 12 weeks (at max dose)

Phentermine (Adipex)

• Approved for SHORT-TERM USE ONLY (≤ 3 months)

• C-IV control

• 8-37.5 mg daily as QD or BID

• Dose adjustments

  • eGFR 15-29 → max 15 mg/day

  • eGFR < 15 → AVOID

Phentermine (Adipex): contraindications

• CVD (arrythmias, CAD, HF, uncontrolled HTN)

• hyperthyroidism

• glaucoma

• hx of drug abuse

Phentermine (Adipex): ADEs

• CV

  • HTN

  • Tachycardia

• CNS

  • dizziness/HA

  • insomnia/psychosis

• GI

  • N/D/C

  • Xerostomia

• Neuromuscular

  • tremor

Phentermine/Topiramate XR (Qsymia)

• 3.75-15/23-92 mg QD dosing

• C-IV Control

• Dose adjustments

  • CrCl < 50 → max dose: 7.5/46 mg

  • CrCl < 30 → AVOID

• MUST TAPER on and off

• Only available through REMS

  • Requires MONTHLY pregnancy testing during use

Phentermine/Topiramate XR (Qsymia): ADEs

• Increased HR

• CNS (mood changes, anxiety, depression, insomnia)

• Decreased serum K+ and bicarb → metabolic acidosis [electrolytes]

• Kidney stones

Phentermine/Topiramate XR (Qsymia): contraindications

• Hyperthyroidism

• Glaucoma

• Use of MAO-Is

• Pregnancy

Phentermine/Topiramate XR (Qsymia): DDIs

• avoid w/

• may decrease effect of

• may lead to

• avoid w/

  • alcohol

  • carbonic anhydrase inhibitors

• may decrease effect of

  • hormonal contraceptives

• may lead to

  • increased risk of hypokalemia when combined w/ thiazide or loop diuretics

Phentermine/Topiramate XR (Qsymia): Monitoring

• Weight

• Resting HR and BP

• Mood

• Symptoms of glaucoma

• ADEs

• Electrolytes and SCr (bicarb, K)

Phentermine/Topiramate XR (Qsymia):

• counseling

• follow up

• counseling

  • take in AM ± food d/t insomnia (want to be able to sleep)

• follow up

  • weight

  • resting HR and BP

  • mood swings

  • glaucoma symptoms

  • ADEs

  • increased SCr

  • decreased bicarb, K+

Naltrexone/Bupropion ER (Contrave)

• dose

• dosing schedule

• 8/90 mg → 32/360 mg

• Dosing schedule

  • Week 1: 1t QAM

  • Week 2: 1t BID

  • Week 3: 2t QAM + 1t QHS

  • Week 4: 2t BID

Naltrexone/Bupropion ER (Contrave)

• ADE

• BBW

• ADEs

  • Tachycardia, HTN

  • N/V/C

  • HA

• BBW for suicidality with depression

Naltrexone/Bupropion ER (Contrave): contraindications

• concomittant use of other bupropion products

• Uncontrolled HTN

• Chronic opioid use

• Seizure disorders

• Patients undergoing withdrawal from AIMS medications

• anorexia/bulimia

• Use of MAO-Is

Naltrexone/Bupropion ER (Contrave): DDIs

• Avoid with alcohol (lowers seizure threshold)

• Opioids + (tramadol, buprenorphine, methadone)

• Dopaminergic drugs

• Other meds containing bupropion or naltrexone

Naltrexone/Bupropion ER (Contrave)

• monitoring

• counseling

• Monitoring

  • Weight

  • BP and HR

  • BG

  • renal/liver

  • Changes in mood

  • ADEs

• Counseling

  • Do not take with a high fat meal

Orlistat dosing

• Alli (OTC)

• Xenical

• Alli → 60 mg TID

• Xenical → 120 mg TID ≤ 60 minutes after meal-containing fat (or with the meal)

  • If there is no fat going through GI tract, meds won’t work on anything

Orlistat: contraindications

• Chronic malabsorption syndrome

• Cholestasis → slowed flow of bile from liver to intestine (slower fat clearance)

• Pregnancy

Orlistat: ADRs

• Decreased fat-vitamin absorption

• GI (improved w continued use)

• MAY develop kidney stones

Orlistat:

• counseling

• monitoring

• counseling

  • Do not take if meal is skipped or does not contain fat

  • Ensure proper supplementation of ADEK and β-carotene

  • Take vitamins 2 hour before or after orlistat → within 2 hours, vites won’t absorb

• weight

  • does not need to be d/c if pt does not acheive ≥ 5% weight loss

Orlistat: DDIs

• Decreased absorption of fat-soluble vitamins

• Separate 4 hours from levothyroxine ← otherwise, reduced absorption/efficacy of levothyroxine

• Monitor INR if on warfarin (can increase)

Liraglutide (Saxenda): dosing

• Liraglutide: 0.6mg inc to 3.0 mg over 5 weeks

  • Multi-dose pen, box of 5 pens if using 3.0 mg/day dose

Semaglutide (Wegovy)

• Semaglutide: 0.25mg inc to 2.4mg over 17 weeks

  • Single-use pen

  • 4 pens per month

  • SAFETY

    • GI and cholelithiasis (gallstones) more common

    • Less common: pancreatitis, cancer, CV events

GLP-1 agonist - Semaglutide: contraindications

• CONTRAINDICATIONS

  • Personal OR FAMILY history of medullary thyroid cancer

  • MEN2 (multiple endocrine neoplasia – tumors in endocrine glands)

Semaglutide injection

• once weekly w/ or w/o food

• SQ

• store in fridge

• RT for up to. 28 days

• scheduled dose

  • more than 2 days away → take missed dose ASAP

  • less than 2 days away → skip dose, take next dose on scheduled day

  • 2+ weeks since last dose → take next dose on scheduled day

Semaglutide injection and oral: more info

• take on empty stomach w/ water

• wait 30 mins before eating, drinking, meds

• swallow whole

• room temp

• dose missed → skip and take next dose following day

• switch from injection → tab

  • 25 mg tab 1x daily for 1 week after d/cing injection

• switch from tab → injection

  • day after tab → initiate 2.4 mg SQ injection once weekly

  • can’t tolerate 25 mg tab → switch to 1.7 mg injection

Tirzepatide (Zepbound)

• contraindications

• ADEs

• CONTRAINDICATIONS – same bc it has a GLP 

  • Personal OR FAMILY history of medullary thyroid cancer

  • MEN2

• ADEs

  • N/D

Tirzepatide (Zepbound): info

• 1x weekly w/ or w/o food

• SQ injection

• multi-dose Kwikpen (must Rx pen needles)

• missed doses can be administered within 4 days of missed dose

• store in fridge

  • single dose good at RT for 21 days

  • kwikpen and multidose goof at RT for 30 days

Ofroglipron (Foundayo)

• dosing

• contraindications

• dosing

  • 0.8 mg → 2.5 mg after 30 days → 5.5 mg → continue or increase after 30 days

• contraindications

  • personal/family hx of medullary thyroid cancer

  • MEN2

Ofroglipron (Foundayo): more info

• 1x daily oral admin

• taken any time of day w/o fasting or water restrictions

• swallow whole

• RT

• missed doses can be taken as soon as remembered, do not double up

Ofroglipron (Foundayo):

• DDI

• Strong CYP3A4 Inhibitors – max dose of Foundayo® is 9 mg once daily when used w/strong CYP3A4 inhibitor

• Avoid concomitant use with strong CYP3A4 inducers

  • May decrease Foundayo® efficacy and need to increase dose

• Do not exceed simvastatin 20 mg once daily when used concomitantly with Foundayo®

• Same DDI w/OCP as tirzepatide

indications

• Semaglutide

• Tirzepatide

• Oforglipron

• Semaglutide

  • ≥ 18 yrs old

  • SQ or PO - overweight or obesity

  • SQ only ≥ 12 yrs old

  • CV risk reduction

  • treatment of MASH (SQ only)

• Tirzepatide

  • ≥ 18 yrs old

  • overweight or obesity + at least one comorbid condition

  • OSA

• Oforglipron

  • ≥ 18 yrs old

  • overweight or obesity + at least one comorbid condition

Compelling indications for WL

• Pre-diabetes, T2DM, or high CV risk → GLP-1 agonists

• Depression → Naltrexone/bupropion

• Obstructive sleep apnea (OSA) → phentermine/topiramate XR, GLP-1 agonists (specifically tirzepatide)

• Current tobacco use (with desire to quit) → Naltrexone/bupropion

• Food cravings → Naltrexone/bupropion

• Metabolic dysfunction → GLP-1 agonists (specifically semaglutide)

weight loss

• ≥5%

• ≥10%

• ≥15%

• ≥5% sustained weight loss improves insulin sensitivity, BP, and lipids

• ≥10% sustained weight loss is usually required to improve most obesity-related diseases

• ≥15% weight loss may be needed for sleep apnea, metabolic steatohepatitis, and HFpEF

• — and — provide greatest weight reduction

• — and — → highest efficacy

• GI effects common w/ — and —

• GLP-1 RA and dual GIP/GLP-1 R

• Semaglutide and tirzepatide → highest efficacy

• Gastrointestinal adverse effects common with semaglutide, and tirzepatide