Obesity Therapeutics

obesity complications

-metabolic syndrome

-prediabetes

-T2DM

-Dyslipidemia

-HTN

-Nonalcoholic fatty liver disease

-Polycystic ovary syndrome

-Female infertility

-OSA

-asthma

-osteoarthritis

-Urinary stress incontinence

-GERD

-Depression

10%

What is the goal weight loss with metabolic syndrome?

prevent T2DM

What is the goal for tertiary prevention of metabolic syndrome?

10%

Goal weight loss with prediabetes:

prevention or delay T2DM

Goal for tertiary prevention of prediabetes:

5-15% or more

Goal weight loss for T2DM:

reduce A1c, reduce meds, diabetes remission

Goal for tertiary prevention of T2DM:

5-15% or more

Goal weight loss of Dyslipidemia:

lower TGs, raise HDL, lower non-HDL

Goal for tertiary prevention of Dyslipidemia:

5-15% or more

Goal weight loss for HTN:

lower BP, reduce meds

Goal for tertiary prevention for HTN:

5% or more (10-40% for steatohepatitis)

goal weight loss for nonalcoholic fatty liver disease:

reduction in itrahepatocellular lipid, reduction in inflammation and fibrosis (if statohepatitis)

Goal for tertiary prevention with nonalcoholic fatty liver disease:

5-15% or more

goal weight loss for polycystic ovary syndrome:

Ovulation, regular menses, reduce hirsutism, increase insulin sensitivity, reduce androgen levels

goal for tertiary prevention with polycycstic ovary syndrome:

10% or more

Goal weight loss for female infertility:

ovulation, preg, live birth

goal for tertiary prevention with female infertility:

7-11% or more

goal weight loss for OSA:

improve s/s, decrease apnea-hypopnea index

goal for tertiary prevention with OSA:

7-8% or more

goal weight loss with asthma:

improve FEV1, improved s/s

goal for tertiary prevention of asthma:

5-10% or more

goal weight loss for osteoarthritis:

improved s/s, increased function

goal for tertiary prevention of osetoarthritis:

5-10% or more

goal weight loss for urinary stress incontinenece:

reduce incontinenece episode frequency

goal for tertiary prevention of urinary stress incontinence:

10% or more

goal weight loss of GERD:

reduce s/s, frequency and severity

goal for tertiary prevention of GERD:

uncertain

goal weight loss for depression:

reduces depression symptoms, improve depression scores

goal for tertiary prevention of depression:

FDA labeled indications of obesity meds

-BMI ≥ 30

-BMI ≥ 27 + at least 1 weight related condition

-Always as adjunct to diet and physical activity efforts

med options for obesity

-Stimulants: diethylpropion, phendimetrazine, phentermine

-orlistat

-phentermine/topiramate ER

-naltrexone ER/bupropion ER

-liraglutide

-semaglutide

-tirzepatide

-setmelanotide

3.6%

weight loss efficacy of stimulants:

about 3.1%

weight loss efficacy of orlisat:

8.8%

weight loss efficacy of phentermine/topiramate ER

4.8%

weight loss efficacy of naltrexone ER/bupropion ER

4.5%

weight loss efficacy of liraglutide

11.9%

weight loss efficacy of semaglutide

16.2%

weight loss efficacy of tirzepatide

about 10%

weight loss efficacy of setmelanotide

stimulants

-Use: Short-term (few weeks) use as adjunct to lifestyle

-Controlled - Phentermine and diethypropion (CIV); Phendimetrazine (CIII)

cardiovascular disease, uncontrolled HTN, hyperthyroidism, glaucoma, hx of drug abuse, within 14 days after MAO inh use, in agitated states, pregnancy, breast-feeding

CIs for stimulants used for weight loss:

> 16 yrs old

What age are stimulants approved for obesity?

no

Do stimulants have effects on obesity-related disease/complications?

-increase water intake and fiber to help dry mouth and constipation

-avoid taking med in evening to reduce insomnia

What are some strategies to manage the AEs of stimulants?

monitoring for stimulants

HR and BP with starting and increasing doses

Orlistat (Xenical, Alli)

-Use: Chronic weight management when used in conjunction with lifestyle

-Not controlled

preg, chronic malabsorption syndrome, cholestasis

What are the CIs for Orlistat?

Alli

OTC agent of Orlistat at a lower dose and caution if pts have history of nephrolithiasis

12 yrs or older.

What age is approved to take Orlistat?

-demonstrated benefit on BP

-potential benefit in T2DM

What are the effects of Orlistat on obesity related diseases/conditions?

follow low calorie meal plan with < 30% of calories from fat to help with GI effects or avoid high fat meals

What are the strategies used to manage the AEs of Orlistat?

Monitoring and Suggestions with Orlistat

-Advise that GI effects usually improve in 4 weeks

-Use multivitamin with fat-soluble vitamins within 2 hours before or after administration in evening to avoid deficiencies

phentermine/topiramate (Qsymia)

-Use: Chronic weight management, as adjunct to lifestyle

-Controlled - C-IV

hyperthyroidism, glaucoma, use during or within 14 days of MAOi, preg

What are the CIs with phentermine/topiramate (Qsymia)?

12 yrs and older

What age do you have to be to take phentermine/topiramate (Qsymia)?

potential benefit in T2DM, orthotic sleep apnea

What effects does phentermine/topiramate (Qsymia) have on obesity-related diseases/complications?

-Increase water intake to help dry mouth, constipation, and reduce kidney stones

-Increase fiber to help constipation

-Avoid taking medication in evening to reduce insomnia

-Paresthesia or cognitive changes may improve with reducing the dose

Strategies to manage AEs of Phentermine/Topiramate (Qsymia):

suggestions and monitoring for phentermine/topiramate (Qsymia)

-counsel on need for effective contraception

-monitor for mood changes, HR, and renal function

naltrexoneER/bupropionER (Contrave)

-Use: Chronic weight management, as adjunct to lifestyle

-Not controlled

CIs with naltrexoneER/bupropion ER (Contrave)

chronic opioid or opiate agonist, acute opiate withdrawal, uncontrolled HTN, seizures, eating disorders, abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptics, concomitant and within 14 days of MAO inh, methyleneblue, linezolid, pregnancy

18 yrs and older

What age is naltrexoneER/bupropionER (Contrave) approved for?

Suicidality in those < 24

What is the BW for naltrexoneER/bupropionER (Contrave)?

potential benefit in T2DM

What is the effect of naltrexoneER/bupropionER (Contrave) on obesity-related diseases/complications?

strategies to manage AEs of naltrexoneER/bupropionER (Contrave)

-Reduce portion size to help nausea

-Increase water and fiber to help dry mouth and constipation

-Administer evening dose at least 3 hr before bedtime to reduce insomnia

-Avoid high fat meals due to increased absorption

Clinical suggestion and monitoring for naltrexoneER/bupropionER (Contrave)

-Monitor blood pressure at initiation and after dose increases

-Monitor for mood changes

liraglutide (Saxenda)

-Use: Chronic weight management, as adjunct to reduced-calorie diet and increased physical activity

-Not controlled

-use with or without food

Cis with Liraglutide (Saxenda)

Contraindications: History or family history of medullary thyroid cancer (boxed warning), or if multiple endocrine neoplasia syndrome type 2 (MEN2), pregnancy

12 yrs and older

What age is Liraglutide (Saxenga) approved for?

-Demonstrated benefit in T2DM

-Potential benefit on blood pressure, ASCVD, MASH, orthotic sleep apnea, and osteo arthritis

What are the effects of Liraglutide (Saxenda) on obesity-related diseases/complications?

strategies to manage AEs of Liraglutide (Saxenda)

-Reduce portions to help nausea

-Increase water and fiber to help manage constipation

-Avoid eating within 2 hrs of bedtime to reduce dyspepsia

Suggestions and Monitoring for Liraglutide (Saxenda)

-Rotate injection sites

-Refrigerate before using

-Monitor for hypoglycemia if on insulin or sulfonylureas

-Monitor heart rate and mood changes

semaglutide (Wegovy)

-Use: Chronic weight management, as adjunct to reduced-calorie diet and increased physical activity

-Not controlled

-Injectable formulation can be used with or without food.

-Oral formulation needs to be taken on empty stomach with up

to 4 oz H20 30 min before meds/food.

-Use contraception during dose escalation.

CIs with Semaglutide (Wegovy)

History or family history of medullary thyroid cancer (boxed warning), or if multiple endocrine neoplasia syndrome type 2 (MEN2), pregnancy

12 yrs and older

What age is the semaglutide (Wegovy) injection approved for?

18 yrs and older

What age is the semaglutide (Wegovy) tablets approved for?

-Demonstrated benefit in T2DM, blood pressure, ASCVD, MASH, HFpEF, and osteo arthritis

-Potential benefit in orthotic sleep apnea

What are the effects of Semaglutide (Wegovy) on obesity-related diseases/complications?

strategies to manage AEs of Semaglutide (Wegovy)

-Reduce portion size and dietary fat to help nausea

-Increase water and fiber to help manage constipation

-Avoid eating within 2 hrs of bedtime to reduce dyspepsia

Clinical suggestion and monitoring for semaglutide (Wegovy)

-Rotate injection sites

-Refrigerate before using

-Monitor for hypoglycemia if on insulin or sulfonylureas

-Monitor heart rate and mood changes

-Consider a multivitamin to avoid micronutrient deficiencies

-Monitor for diabetic retinopathy in T2DM

-Monitor for symptoms of cholelithiasis

tirzepatide (Zepbound)

-Use: Chronic weight management, as adjunct to reduced-calorie diet and increased physical activity

-Not controlled

Special Considerations:

-Use with or without food.

-Use contraception during dose escalation

CIs with tizepatide (Zepbound)

History or family history of medullary thyroid cancer (boxed warning), or if multiple endocrine neoplasia syndrome type 2(MEN2), pregnancy

-Demonstrated benefit in T2DM, blood pressure, orthotic sleep apnea

-Potential benefit in ASCVD, MASH, HFpEF, and osteoarthritis

What are the effects of tirzepatide (Zepbound) on obesity related diseases/complications?

strategies to manage AEs of Tirzepatide (Zepbound):

-Reduce portion size and dietary fat to help nausea

-Increase water and fiber to help manage constipation

-Avoid eating within 2 hrs of bedtime to reduce dyspepsia

Clinical suggestions and monitoring for tirzepatide (Zepbound)

-Rotate injection sites

-Refrigerate before using

-Monitor for hypoglycemia if on insulin or sulfonylureas

-Monitor heart rate and mood changes

-Consider a multivitamin to avoid micronutrient deficiencies

-Monitor for diabetic retinopathy in T2DM

-Monitor for symptoms of cholelithiasis

Setmelanotide (Imcivree)

-Use: Long-term use in patients with Bardet-Biedl syndrome or deficiencies in POMC, PCSK1, or LEPR

-Not controlled

-Contraindications: eGFR <15 ml/min

-Special Considerations:

• intention to use in a very specific patient group

• Renally dose adjust for eGFR 15-29 ml/min

ages 2 years and older

What age is setmelanotide (Imcivree) approved for?

Implantable Medical Devices

-reversible devices that may be removed

-may be desirable choice for candidates who may not qualify for surgery or may not wish to undergo surgical type of procedure

Maestro Rechargeable System

-Pace-maker type device implanted on vagal trunk that intermittently blocks communication with the vagus nerve through electric impulse

-9% weight loss after 1 year J.T DiPiro, et al. Pharmacotherapy

Gastric Balloon Systems

-Weight loss ranges from ~7-12%

-Avoid NSAIDs and Anticoagulants due to risk of ulcers/bleeding; also chronic steroids can impair stomach lining and delays healing

-Proton pump inhibitors should be taken concomitantly to prevent ulcers

Obalon Balloon System

-Only balloon system that doesn't have to be endoscopically

placed (patients instead swallow the encapsulated system)

-Nausea treatment may be needed, especially early on

Spatz3 Balloon System

-First adjustable balloon

-CAUTION: use with serotonin drugs increases risk of serotonin

syndrome if balloon ruptures (due to methylene blue

Orbera Balloon System

more weight loss than other systems

qualifications for Bariatric Surgery

-BMI ≥ 35 kg/m2 (32.5-37.4 kg/m2 in Asian Americans)

-BMI 30 to 34.9 kg/m2 (27.5-32.4 kg/m2 in Asian Americans) with diabetes mellitus or metabolic syndrome

-Ages 13-18 with BMI ≥ 35 kg/m2 or ≥ 120% of the 95th percentile for age (whichever is lower) with a severe comorbidity

-Ages 13-18 with BMI ≥ 40 kg/m2 or ≥ 140% of the 95th percentile for BMI (whichever is lower) with any obesity-related comorbidity

Adjustable gastric band (lap band)

surgery weight loss of about 20-25%

vertical sleeve gastrectomy

surgery weight loss of about 25-30%

Roux-en-Y Gastric Bypass

surgery weight loss of about 30-35%

Billiopancreatic Diversion with Duodenal Switch

surgery weight loss of 35-45%

-nutritional deficiency risk

-altered absorption (reduced contact time leads to altered kinetics)

What are some post surgery medication considerations?

nutritional deficiency risk after weightloss surgery

Daily supplementation with adult multivitamin plus minerals, elemental calcium, vitaminD, folic acid, thiamine, elemental iron, and vitamin B12 is essential

altered absorption after weight loss surgery

-Avoid direct oral anticoagulants or NSAIDs post-surgery (bleed risk)

-Medication concentrations that may be reduced: SSRIs, antipsychotics, tamoxifen, oral contraceptives, some antibiotics

-Proton pump inhibitors may be used post-surgery to prevent ulcers

-May need liquid formulations or open capsules post-surgically (especially first few months)

-Monitor narrow therapeutic meds closely (warfarin, levothyroxine, lithium)

-May prefer IR formulations to ER or CR

-IV bisphosphonate may be preferred formulation If needed for bone loss

weight promoting Hypertensive agents

-alpha blockers

-metoprolol

-propranolol

-atenolol