Weight Modifying agents and Nutrition

List of meds that cause weight increase

• Insulin • Sulfonylureas • Anti-retrovirals • Thiazolidinediones • Some antidepressants (varies by agent MOA)

• TCAs, SSRIs • Antipsychotics • Some anticonvulsants (varies by agent MOA) • Some beta-blockers • Glucocorticoids

Lists of meds that cause weight decrease

Buproprion, Topiramate, Semaglutide, liraglutide. Tirzepatide

Underweight BMI?

<18.5

Ideal BMI?

18.5-24.9

Overweight BMI?

25-29.9

Obesity Class 1 BMI?

30-34.9

Obesity Class 2 BMI?

35-39.9

Obesity Class 3 BMI?

40 and above

What hormones increase post prandial?

• Insulin

• Ghrelin

• Peptide YY (from ileum and colon)

• Cholecystokinin (from duodenum)

• Leptin (from adipose tissues)

Examples of short term agents for weight loss?

Phentermine (Adipex-P) and Diethylpropion

Are short term agents recommended by current guidelines?

NO, as soon as you stop weight gain returns, no long term benefit, abuse potential

Warnings/ Precautions associated with short term agents?

CVD, Diabetes, Renal impairment, seizure disorders

ADR profile of short term agents?

increased BP, pulse, acute MI, arrhythmias, CNS effects

Long term obesity agents?

• Orlistat

• Phentermine/Topiramate

• Naltrexone/Bupropion

• Liraglutide

• Victoza for DM

• Semaglutide

• Ozempic for DM

• Tirzepatide

• Mounjaro for DM

Orlistat MOA?

Reversible lipase inhibitor (gastric and pancreatic lipases), Blocks absorption of fat in the diet (~30%) in the stomach and small intestine

Orlistat SE?

Mostly GI, usually happens early and is worse with fatty meals

Orlistat precautions/ CI?

Cholestasis or gallstones, may inhibit some absorption, CI in patients with existing malabsorption, caution in patients with kidney stones

Phentermine MOA?

sympathomimetic amine (central norepinephrine release)

Topiramate extended release MOA?

GABA effect, glutamate receptor inhibition, carbonic

anhydrase inhibition

When do you take phentermine/ Topiramate?

In the morning (stimulatory effects)

FDA REMS for phentermine/ Topiramate?

Limited in which pharmacies can dispense (several

criteria including staff training, patient education materials on reproductive issues, etc) - certified pharmacies

What medication has Increased risk of congenital malformation, specifically orofacial clefts, in

infants exposed to Qsymia during the first trimester of pregnancy?

Phentermine/ Topiramate

Phentermine/ Topiramate SE?

• Paresthesia

• Headache

• Dizziness

• Dysgeusia

• Insomnia

• Anxiety

• Irritability

• Attention disturbance

• Alopecia

• Hypokalemia

Conditions phentermine/ Topiramate is CI in?

Pregnancy, Glaucoma, hyperthyroidism, mood or sleep disorders

phentermine/topiramate monitoring?

Heart rate in pt with CVD, monitor electrolytes, counsel women of childbearing potential of tetragenic potential

Naltrexone MOA?

opioid antagonist (increased binding of beta-endorphin to µ-opioid receptors)

Buproprion MOA?

Norepinephrine and dopamine reuptake inhibition

Naltrexone/ Buproprion SE?

• Nausea (30%) • Headache (14%) • Constipation (15%) • Dizziness (9%) • Dry mouth (7.5%) • Hot flushing (5%) • Hypertension (3%)

BBW for naltrexone & bupropion?

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS in children, adolescents,

and young adults

• FDA required warning for all antidepressants

• Younger adult patient is NOT a contraindication for use

Naltrexone/ Buproprion CI?

• Uncontrolled HTN

• Seizure disorder, anorexia

• Use of other bupropion products

• Chronic opioid use

• Pregnancy

Caution in ___ with naltrexone and Buproprion?

• Suicidal behavior / ideation

• h/o seizure disorder

• HTN/CVD: monitor BP and pulse

Side effects associated with GLP1 and GIP?

Increase risk of MENS2 and MTC, Pancreatitis, sarcopenia, diarrhea/ constipation, delayed gastric emptying, DM eye disease

GLP-1 Liraglutide?

Daily injection

GLP-1: Semaglutide?

Weekly injection

Dulaglutide information?

• DM indication only (Trulicity)

• High dose "4.5 mg"

• Weight loss: ~5-6%

Tirzepatide information?

• Combination GLP-1 agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist

• aka 'Twincretin' (GLP and GIP agonism)

•Once-weekly, subcutaneously, PEN

• Similar SE/precuations as GLP1RA/GIP

AGA guidelines for chronic disease?

= Chronic therapy

• All with comprehensive lifestyle interventions

• Diet, exercise, and behavoirs

What order do you give weight loss medications based on percent weight loss?

• Semaglutide

• Liraglutide

• Phentermine-Topiramate ER

• Naltrexone-Bupropion ER

What is the highest weight loss on the market (as of now)?

Tirzepatide

AGA recommended against the use of ____?

Orlistat

Discontinuing criteria for Orlistat?

No specific weight loss requirements before discontinuing agent (ie risks > benefits)

Discontinuing criteria for Naltrexone/ Buproprion and phentermine/ topiramate?

At least a 5 % weight loss after 12 weeks of therapy at maximum tolerated dose

Discontinuing criteria for Liraglutide?

Discontinue agent if not at least a 4% weight loss after 16 weeks at the maintenance dose or cannot tolerate the maintenance dose (3 mg)

• Don't settle for less than 3 mg

Discontinuing criteria for semaglutide?

Discontinue agent if cannot tolerate the maintenance dose (either 1.7 or 2.4 mg subcut)

• Don't settle for less than 1.7 mg

• NO % weight loss requirement

What 3 principals to keep in mind for postoperative management of bariatric procedures?

• Micronutrient deficiencies are common in obese patients , even before bariatric surgery

• What is the anatomy of the GI tract after the surgery?

• Was malabsorption surgery performed?

Yes → Highest risk of malabsorption of drugs and nutrients

Drug therapy postoperatively?

Utilitize liquid or crushable forms, avoid enteric coated ER formulations, Avoid estrogen oral formulations, avoid NSAIDS

Malabsorptive procedures decrease intestinal length→

reduced absorption of ER products, delayed release, and enteric coated products

What three FDA agents are approved for weight gain?

• Dronabinol (CIII)

• Megestrol

• Oxandrolone (CIII)

Dronabinol MOA?

Synthetic THC, thought to have effect on cannabinoid receptors in the CNS (CB1 and CB2),may inhibit activity in the vomiting center

ADR with Dronabinol?

Xerostomia (38-50%), dizziness (3-10%), somnolence (3-10%),

anxiety, euphoria, GI pain

Precautions/ CI with Dronabinol?

addiction potential, limit use with drugs having similar psychiatric effect, CNS ADRs, seizure DO (may lower threshold), Watch closely in elderly for neurological / psychoactive effects especially when using other CNS meds

Megestrol MOA?

synthetic progestin (antiestrogenic properties) thought to

antagonize effects of catabolic cytokines

Megestrol ADRs?

GI side effects, impotence in men, DVT/PE, hot sweats,

insomnia

Megestrol Precautions/ Contraindications?

• Pregnancy (C)

• Caution with h/o or at risk for DVT/PE

Oxandrolone MOA?

Synthetic testosterone derivative, provides androgenic/anabolic action thought to

promote protein anabolism / reverse catabolic processes

ADR for oxandrolone?

edema, testicular atrophy, hair growth, voice deepening, menstrual irregularities, cholesterol increase, liver damage

Precautions/Contraindications for Oxandrolone?

• Contras: Pregnancy, hypercalcemia

• Caution in those with CVD that edema or increased cholesterol could make worse

Efficacy of FDA approved agents for weight gain?

• Dronabinol appears better at reducing N/V than increasing weight

• Megestrol effective at increasing weight but mostly in the form of fat

• Oxandrolone effective in increasing weight and lean body mass / fat

Unapproved agents for weight loss: Cyproheptadine?

• Antihistamine

• Commonly used in children if nonpharmacological approaches fail

• ADRs: Similar to other sedating antihistamines

Unapproved agents for weight loss: mirtazapine?

• Antidepressant

• Too often used in elderly losing weight / some data to support

• ADRs: somnolence, xerostomia, constipation, elevated TG