TREATING OBESITY WITH MEDICATION

Treah Haggerty MD, MS - Associate Professor | WVU Department of Family Medicine - Obesity Medicine Physician | WVU Medical Weight Management

OBJECTIVES

1. Participants will understand obesity is a disease.

2. Participants will be able to list necessary components of the clinical encounter for anti-obesity medications.

3. Participants will be able to identify and understand the use of antiobesity medications.

RX ANTI OBESITY MEDICATIONS (AOM)

o Effective Adjunct to treatment of patient with obesity

o May improve metabolic complications of obesity

OBJECTIVE TO AOM o Treat disease

o May help manage eating behaviors

o Slow progression of weight gain

o Lifestyle benefits (movement, quality of life, pain)

OBESITY AS A DISEASE

o The AMA defined obesity as a disease in 2013.

o Obesity has genetic, biological, and environmental factors which play a role in the resistance to treatment

Treatment of obesity, weight loss, has many benefits

o Risk factor improvement

o Prevention of comorbidities

o Improvement in feeling and function

OBESITY AS A DISEASE

Table from Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2015 Feb 1;100(2):342-62.

OBESITY AS A DISEASE Figure is from Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2015 Feb 1;100(2):342-62.

POMC/CART

o Anorexigenic (Promote Satiety)

o Located in the Arcuate Nucleus

o Stimulated by multiple hormones (leptin, GLP1, PYY…)

NPY/AgRP

o Orexigenic (Promotes Eating)

o Located in the Arcuate Nucleus

o Stimulated by Ghrelin

Leptin

o Released by adipose tissue

o Stimulates on POMC/CART -> stimulates MC4R

o Inhibits NPY/AgRP

o STOP EATING (Anorexogenic)

Grelin

o Released by the stomach

o Stimulates NPY/AgRP -> stimulates Y1R

o START EATING (orexogenic)

o Increases with time since eating

Intestines

oRelease Anorexigenic hormones oPeptide YY (PYY) oCholecystokinin

(CCK) oGLP1

OBESITY AS A DISEASE Weight Reduction

o Food restriction is counteracted by biological responses to weight loss

o We see a drop in energy expenditure and increase in appetite with weight loss

OBESITY AS A DISEASE

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine. 2011 Oct 27;365(17):1597-604.

OBESITY AS A DISEASE

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine. 2011 Oct 27;365(17):1597-604.

OBESITY AS A DISEASE

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine. 2011 Oct 27;365(17):1597-604.

OBESITY AS A DISEASE

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine. 2011 Oct 27;365(17):1597-604.

OBESITY AS A DISEASE

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine. 2011 Oct 27;365(17):1597-604.

AOM IMPORTANT PRINCIPLES

o Variable weight loss

o Variable time frame

o Expect 5-10% weight loss for most

WHO ARE WE PRESCRIBING

o Diagnosis of Obesity (BMI > 30)

o BMI >= 27 and one adiposity complication

Adiposity Complication High Blood Pressure High Cholesterol Type 2 Diabetes Coronary Heart Disease Stroke Osteoarthritis Sleep Apnea / Restrictive Lung Diseases

WHO ARE WE PRESCRIBING

o Diagnosis of obesity

o Build rapport

o Ask permission

o Use appropriate terms

AOM IMPORTANT PRINCIPLES

Diet Exercise

Behavior Change

Medication

o 4 Prong Approach

ANTI-OBESITY MEDICATIONS

o Phentermine o Orlistat o Locarsarin o Liraglutide oNaltrexone/Bupropion oPhentermine/Topiramate

PHENTERMINE

DEA Schedule IV Stimulant (Sympathomimetic amine)

Norepinephrine reuptake inhibitor

Approved for short term use (12 weeks)

Expect about a 5% loss in some patients

Side Effects: Headache, high blood pressure, rapid or irregular heart rate, overstimulation, tremor, insomnia

Contraindications: Overactive thyroid, Uncontrolled high blood pressure, seizure disorder, cardiovascular disease, glaucoma, active drug abuse, agitated state

Interactions: MAO inhibitors, sympathomimetics, alcohol, adrenergic neuron blocking drugs

PHENTERMINE

Dose: Phentermine Resin = 37.5mg/day.

Advantages: Inexpensive

Disadvantages: Extensive side effect profile

ORLISTAT

Gastrointestinal Lipase Inhibitor

Approved for OTC (lower dose than prescription)

Expect about 5% loss

Side Effects: Oily discharge from rectum, promote gallstones and kidney stones, malabsorption of fat soluble vitamins (A,D,E,K)

Contraindications: Malabsorption syndrome and cholestasis

Recommendation: Take a multivitamin daily

Interactions: Cyclosporines, hormone containing contraceptives, seizure medications, thyroid hormones, warfarin

ORLISTAT

Dose: 120mg three times daily Advantages: Not systemic (also a disadvantage), cheaper. Can help with constipation Disadvantage: Side effects

LORCARSERIN

Womp womp

LIRAGLUTIDE

Glucagon-like peptide 1 receptor agonist

Normally used in Type 2 diabetes at half the dose (1.8 mg)

Approved for weight loss at 3 mg daily dose

Adverse Effects: Nausea, hypoglycemia, diarrhea, vomiting, headaches, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increase lipase, renal insufficiency.

Contraindications: Family history of medullary thyroid cancer or type 2 multiple endocrine neoplasia syndrome

Interactions: May slow gastric emptying so could impact absorption of other medications.

LIRAGLUTIDE

Dosing: 3 mg daily (Prescribed as 0.6 once daily for a week then 1.2mg once daily for a week, then 1.8mg once daily for a week, then 2.4mg once daily for a week, then 3mg daily.)

Advantages: Low side effect profile

Disadvantage: Injection, Cost ($$$$$)

LIRAGLUTIDE

Effects:

o Delays gastric emptying

o Decrease liver glucose production

o Increase insulin secretion (glucose dependant)

o Increases glucose uptake by muscles.

NALTREXONE/BUPROPION

Opioid antagonist and reuptake inhibitor of dopamine and norepinephrine

Normally used in depression and opiate use disorder

Adverse Effects: Naltrexone (Nausea, constipation, headaches, vomiting, dizziness) Bupropion ( increase suicidal thoughts, insomnia)

Contraindications: uncontrolled High Blood Pressure, Seizure disorder, or drug/alcohol withdrawal

Interactions: Opioid pain medications, anti seizure medications. MAO inhibitors

NALTREXONE/BUPROPION

Dose: 8 mg/90 mg 2 tablets twice daily. Increased by 1 pill per day each week till max dose (32/360mg daily)

Advantages: Helps with food addiction

Disadvantage: Cost

PHENTERMINE/TOPIRAMATE

DEA Schedule IV Stimulant (Sympathomimetic amine)

GABA receptor modulation (Topiramate) plus norepinephrine reuptake inhibitor

(Phentermine)

Adverse Effects: Nausea, dry mouth, constipation, paraesthesia, dizziness, dysgeusia (distortion of taste), Headache, high blood pressure, rapid or irregular heart rate, overstimulation, tremor, insomnia

Contraindications: Pregnancy or breastfeeding, hyperthyroidism, glaucoma

Interactions: MAO inhibitors, sympathomimetic amines,

PHENTERMINE/TOPIRAMATE

Dose: 3.75/23mg ER QD (starting dose). 7.5/46 mg ER daily (recommended dose)

Advantages: Robust weight loss (>5% in studies)

Disadvantage: Expensive, teratogenic

MONITOR AOM

Medication specific

Monitor patients for clinical improvement across 12-16 weeks. If not hitting a 5% loss from baseline body weight, consider switching increasing current medications dose or switching to a new medication

Take pregnancy plans into consideration

Image from World Obesity Federation

MONITOR AOM

o Monitor patients for efficacy and safety monthly for 3 months

o After determined safe and effective, monitor once every 3 months.

o If a patient’s response to a weight loss medication is deemed effective (weight loss 5% of body weight at 3 mo) and safe, we recommend that the medication be continued. If deemed ineffective (weight loss 5% at 3 mo) or if there are safety or tolerability issues at any time, we recommend that the medication be discontinued and alternative medications or referral for alternative treatment approaches be considered. (Endocrine society recommendation)

RESOURCES

Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2015 Feb 1;100(2):342-62.

The Obesity Algorithm. https://obesitymedicine.org/

Pictures:

https://www.worldobesity.org/resources/image-bank

http://www.uconnruddcenter.org/media-gallery

https://www.obesityaction.org/get-educated/public-resources/oac-image-gallery/

QUESTIONS? Treah Haggerty, MD, MS haggertyt@wvumedicine.org 304-598-4890 – Medical Weight Management 304-598-4000 – Ask to page me Website: www.WVUMedicine.org/weightmgmt Facebook Support Group: https://www.facebook.com/groups/wvumedweightloss/