The Skinny on Weight Loss Meds · Reported Weight Loss Drug Length of Trial Total Weight Loss (kg)...

The Skinny on

Weight Loss

Meds

Kathy H. Sullivan, MSN,

APRN-BC, CDE

No Financial disclosures

Definition of obesity

World Health Organization (WHO)

Abnormal or excessive fat accumulation

that presents a risk to health

Chronic, progressive disease resulting from

multiple environmental and genetic factors

National Institutes of Health (NIH)

A BMI (Body Mass Index) of 30 and above

Prevalence

Global Crisis

65 % of the world’s population lives in

countries where overweight + obesity kill

more people than underweight

Approximately 500 million adults in the

world are affected by obesity

1 billion are affected by being overweight

Medical cost of obesity is reported to be

about $145 billion/year

Obesity Statistics

CDC

> 33% of the US population is obese

Non-Hispanic African Americans with the highest rates, followed by Hispanic population, Caucasions, and Asians

https://www.cdc.gov/nchs/data/databriefs/db219.pdf)PDF-704KB

Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2011

Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.

*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2012

Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.

*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2013

Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.

*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2014

Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.

*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2015

Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.

*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2016

Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011.

*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Comorbid conditions of Obesity

include:

OSA

HLD

HTN

T2DM/GDM

Cancers

Infertility

Fatty Liver Disease

Depression

CVD

Endocrine Society Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

Endocrine Society Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

Evaluating the Obese Patient

History Age of onset of weight

gain Previous weight loss

attempts

Change in dietary patterns

History of exercise Current/past

medications

Smoking cessation Sleeping disorders Eating disorders Family history of obesity

Co-morbid conditions

PE

Measurements

Labs

Fasting

glucose/A1C

Lipid panel

TFTs

LFTs

BMP

Frequent patient FU

All patients prescribed weight loss

medications should be seen at least

monthly for the first three months, then at

least every three months

Best weight loss outcomes occur with

frequent face to face visits (on average

16 visits per year)

Endocrine Society Clinical Practice Guidelines

Weight Altering Medications Commonly taken by Patients

Medical condition Preferred Agents Agents with

weight gain as a

potential side

effect

Type 2 DM GLP1 agonists,

SGLT2 inhibitors,

MTF

Sulfonylureas,

TZDs, Insulin,

Mitglinides

Hypertension ACE-Inhibitors,

ARBs

Beta-blockers

Antidepressants Fluoxetine,

Citalopram,

Escitalopram,

Buproprion

TCA, Mirtazapine,

Paroxetine

Inflammatory

diseases

NSAIDS, disease

modifying anti-

rheumatic drugs

steroids

Weight Altering Meds, cont’d

Medical conditions Preferred Agents Agents with

Weight gain as a

potential side

effects

Anti-epileptic drugs Lamotrigine,

Levetiracetam,

Phenytoin

Gabapentin,

Pregabalin,

Valproic Acid

Anti-psychotics Ziprasidone,

Aripiprazole

Clozapine,

Olanzapine,

Quetiapine,

Risperidone,

Seroquel

Oral

Contraceptives

IUDs, barrier

methods

OCPs

Khan S, Horn DB, Still C. Insights into the Patient Population with Obesity. Bariatric Times. 2016; 13: Supplement C

The Role of Medications in Weight Loss

They do not work on their own !!

Need to incorporate lifestyle changes first….

The addition of a weight loss medication

will likely result in greater weight loss

Pharmacological Treatment

General Recommendations

BMI Recommendation

> 25 Lifestyle Management

> 27 with comorbids OR

> 30

Pharmacologic

> 35 with comorbids OR

> 40

Bariatric Surgery

Endocrine Society Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

Three Major Groups of Medications:

Centrally acting medications that impair

dietary intake.

Medications that act peripherally to impair

dietary absorption

Medications that increase energy

expenditure.

There are 5 FDA approved drugs for

long term use for weight loss in the US

1. Phentermine/Topiramate (schedule IV)

2. Orlistat

3. Naltrexone/Buproprion

4. Liraglutide

5. Lorcaserin (schedule IV)

AACE/ACE Algorithm For The Medical Care of Patients With Obesity. 2016.

AACE/ACE Algorithm For The Medical Care Of Patients with Obesity. 2016.

Phentermine/Topiramate

(Qsymia) Dose: Starting dose 3.75 mg/23 mg, then on day 15 increase to

7.5 mg/46 mg daily x 12 weeks, if not lost 3% discontinue or escalate. If escalate, 11.25 mg/69 mg daily x 14 days, then 15 mg/92 mg x 12 weeks. If not lost at least 5% on higher dose, discontinue gradually.

Formulation: Capsule

MOA: GABA receptor modulation, norepinephrine releasing agent

Average Weight Loss: Recommended dose 6.6 kg / 14.5 lbs; high dose 8.6 kg / 18.9 lbs

Status: Approved in 2012 for chronic management

Side Effects: Paresthesia, constipation, dry mouth, insomnia, dizziness, altered sense of taste, nephrolithiasis

Contraindications: Pregnancy/breast feeding, glaucoma, hyperthyroidism, MAOI, sympathomimetics

Scheduled Medication

Orlistat

(Alli, Xenical)

Dose: Xenical Rx only – 120 mg p.o. q8hrs; Alli 60 mg p.o. q8hrs

Formulation: Capsule

MOA: Pancreatic and gastric lipase inhibitor

Average Weight Loss: 2.9 - 3.4 kg / 6.5 – 7.5 lbs

Status: Approved in 1999 for chronic management

Side Effects: Fecal incontinence, defecation, steatorrhea, fecal urgency, flatulence, decreased absorption of fat soluble vitamins

Contraindications: Warfarin, levothyroxine, malabsorption syndrome, pregnancy/breast feeding, cholestasis, antiepileptics, cyclosporine

Naltrexone/Bupropion

(Contrave)

Dose: Target dose 32 mg/360 mg achieved at start of week four. 8 mg/90 mg daily during week 1, increase by 1 tablet daily each week until 2 tablets twice daily.

Formulation: Extended Release Tablet

MOA: Combo is thought to regulate the dopamine reward system to help control eating patterns. Naltrexone specifically blocks opioid receptors. Bupropion increases dopamine activity.

Average Weight Loss: 4.8 %

Status: Approved in 2014 for chronic management Side Effects: GI, dizziness

Contraindications: Seizure disorder, eating disorder, MAOI, uncontrolled hypertension, drug/alcohol withdrawal

Liraglutide

(Saxenda)

Dose: 3 mg injected (0.6 mg x 1 week daily, increase by 0.6 mg weekly until 3 mg dose achieved)

Formulation: Injectable

MOA: GLP-1 agonist

Average Weight Loss: 5.8 kg

Status: Approved in 2014 for chronic management

Side Effects: GI, pancreatitis

Contraindications: Medullary thyroid cancer, MEN 2, insulin therapy

Above dosing not approved for diabetes management (Victoza)

Lorcaserin

(Belviq)

Dose: 10 mg p.o. BID or 20 mg p.o. daily

Formulation: Tablet, Extended release tablet

MOA: 5HT2c receptor agonist (anorexigenic neurons in hypothalamus)

Average Weight Loss: 3.6 kg / 7.9 lbs

Status: Approved in 2012 for chronic management

Side Effects: Nausea, dry mouth, dizziness, constipation

Contraindications: Pregnancy/breast feeding, use caution with other serotonergic medications

Phentermine (Adipex, Lomaira)

Dose: 15 – 37.5 mg/day in 1-2 divided doses; Lomaira 8 mg TID

Formulation: Capsule, Tablet, ODT

MOA: Norepinephrine releasing agent

Average Weight Loss: 3.5 kg / 7.9 lbs

Status: Approved for short term use (3 months)/ Approved in 1960s

Side Effects: Multiple

Contraindications: Anxiety, seizure, uncontrolled hypertension, history of heart disease, MAOI, pregnancy/breast feeding, glaucoma, hyperthyroidism, history of drug use, other sympathomimetics

Scheduled Medication

Phentermine, cont’d

Long term Phentermine use is OFF LABEL, but

used widely primarily due to its favorable

cost. It may be reasonable to continue

long-term treatment with Phentermine to

prevent weight gain as long as the OFF

LABEL use is disclosed to the patient, and

there are no serious CVD, psychiatric

disease, history of substance abuse of any

significant increase in HR or BP

Reported Weight Loss Drug Length of

Trial

Total

Weight

Loss (kg)

Percent

weight

loss

Cost

(USD/

month)

Phentermine 13 weeks 6.4 4 45

Orlistat > 52

weeks

5.3 4 45,

207

Lorcaserin 52 weeks 5.8 3 240

Phentermine/

Topiramate

> 52

weeks

10.2 9 195

Bupropion/

Naltrexone

>52

weeks

6.1 5 55

Liraglutide 3.0 mg 24 weeks 2.8 5 1000

References

1. Vilsboll et al, BMJ 2012, 344:d7771 5. Khera R et al, JAMA. 2016;315(22):2424-2434.

2. LeBlanc ES et al, Ann Intern Med, 2011, 155:434

3. UpToDate, accessed 9/17/16.

4. Yanovski SZ et al, JAMA 2014;311(1):74

Virtually all weight loss medications in the US

have the same thing in common….

Medication

Denied as 'Not a

Covered Benefit'

Monthly cost for self-pay (without coupon)

Medication # of pills cost

Qysmia caps 3.75/23 mg 30 $218.12

Qysmia caps 7.5/46 mg 30 $223.20

Qysmia caps 11.25/69 mg 30 $239.40

Qysmia caps 15/92 mg 30 $239.40

Alli 60 mg (OTC) 120 $77.93

Xenical 120 mg (Rx) 90 $748.22

Contrave tabs 8/90 mg 120 $333.58

Saxenda pen 18 mg/3ml 5 pens $1440.50

Belviq 10 mg 60 $317.93

Belviq 20 mg XR 30 $317.93

Monthly cost, cont’d

Medication # of pills cost

Phentermine 15 mg caps 30 $27.95

Phentermine 30 mg caps 30 $27.95

Phentermine 37.5 mg XR tabs 30 $19.95

Trokendi 25 mg XR 30 $332.00

Trokendi 50 mg XR 30 $412.00

Trokendi 100 mg XR 30 $822.38

Trokendi 200 mg XR 30 $1124.97

Serotonin Syndrome

Potentially life threatening condition associated with increased serotonergic activity in the

central nervous system

Clinical Diagnosis – no laboratory test to confirms

s/sx: mental status changes – anxiety, agitated delirium, restlessness and disorientation. Can also include diaphoresis, tachycardia, and

hyperthermia

Physical Examination findings

in Serotonin Syndrome

Tachycardia

Hypertension

Hyperthermia

Agitation

Dilated pupils

Tremors

Deep tendon

hyperreflexia

Ocular clonus

Inducible or spontaneous muscle clonus

Muscle rigidity

BL Babinski signs

Dry mucous membranes

Flushed skin

Increased bowel sounds

Majority of cases of serotonin syndrome present

within 24 hours and most within six hours of a

change or initiation of a drug

It is seen with therapeutic medication use,

inadvertent interactions

Observed in all age groups including newborns

and the elderly

SSRIs are the most common medications

associated with diagnosis

Estimate of Bariatric Surgery Numbers, 2011-2016

2011 2012 2013 2014 2015 2016

Total 158,000 173,000 179,000 193,000 196,000 216,000

RNY 36.7% 37.5% 34.2% 26.8% 23.1% 18.7%

Band 35.4% 20.2% 14% 9.5% 5.7% 3.4%

Sleeve 17.8% 33% 42.1% 51.7% 53.8% 58.1%

BPD/DS 0.9% 1% 1% 0.4% 0.6% 0.6%

Revisions 6% 6% 6% 11.5% 13.6% 13.9%

Other 3.2% 2.3% 2.7% 0.1% 2.3% 2.6%

Balloons 0.03 2.7

V-bloc 18

cases

ASMBS total bariatric procedures numbers from 2011, 2012, 2013, 2014,2015, and 2016 are based on the best estimation form available data (BOLD, ASC/MBSAQIP, National Inpatient Sample data and outpatient estimates)

Bariatric Procedures Performed at CCHS

2016 ~ 648 cases

59% sleeve

13% bypass

11 %

conversion/revision

17 % other

revision/band

removal

0.2% banding

2017 ~ 616 cases

62% sleeve

15 % bypass

9 %

conversion/revision

13 % other

revision/band

removal

0.8 % banding

0.5 % DS

Case study #1: 55 yo male with

metabolic syndrome

CC: Cannot lose weight despite personal training 3x/wk

FH: DM, CAD

Meds: Atenolol

Valsartan

Glipizide twice a day

Pioglitazone

MTF

Atorvastatin

Glargine Insulin

Data:

Wt 264 lbs

Ht 5’ 10”

BMI 38kg/m2

Waist 45 in

BP 150/95

A1C 7.2

FBG 150-175

To Chol 220

Trigs 300

LDL-C 130

HDL 40

Case #1, questions

1. Before starting a low-calorie diet, you

would want to stop/re-think:

1. Pioglitazone

2. Glipizide 5mg twice a day

3. Atenolol

4. Metformin 500 mg twice a day

5. Insulin 20 units at night

Case Study # 2:, 61 yo female with post

menopausal weight gain

Severe obesity – referred for surgery

Asthma, arthritis, fibromyalgia

Undiagnosed HTN

FH: HTN

Meds: Zafirlukast

Albuterol Inhaler

Metoprolol

Loratadine

Etodolac

paroxetine

Vitamin B, MVI, Calcium

Labs:

Wt: 200 lbs

Ht: 5’ 5”

BMI 33 kg/m2

Waist 34 in

BP 160/95

A1C 5.9

FBS 105

To Chol 250

Trigs 260

LDL 150

HDL 60

Case #2: Questions

Which comorbidities should improve with weight loss ?

1. Asthma

2. Arthritis

3. Fibromyalgia

4. HTN

Which of her medications can case weight gain ?

1. Zafirlukast

2. Loratadine

3. Etodolac

4. Paroxetine

Case Study # 3: 36 yo female referred to me

by bariatric surgeon for significant weight gain

following gastric bypass 2012

Complex medical history

MO, s/p gastric bypass

Depression, chronic migraine syndrome, fibromyalgia, cancer

No history of pancreatitis or personal/family h/o thyroid ca

Meds Cymbalta, Tizanidine, Prevacid, MVI, Zofran, Lamictal, Trazodone, Abilify, Nortriptyline, Advair, Colace, Proair, Calcium +D, Verapamil, Ropinirole, Lyrica, Meclizine, Tylenol w/codeine

Labs

Wt current: 352.5 lbs

Ht: 5’ 5”

BMI: 55.41

BP 110/78 HR 84

BUN 6 creat 0.75

To chol 213

LDL 141

HDL 53

Trigs 87

Glucose 80

Case # 3: questions

Given her medical history, which of these

weight loss medications would you start ?

1. Phentermine

2. Qysmia

3. Belviq

4. Saxenda

What do you do next ?

Conclusion

Obesity is a HUGE concern – locally,

nationally, and worldwide

Significant morbidity and mortality

contribute to health care costs

First line treatment should always be

aggressive lifestyle changes

Prescribe weight neutral medications

whenever possible for other disease states

Patients should understand that successful

treatment requires lifelong treatment

Conclusion, cont’d

So much that we didn’t get to talk about…. CDC guidelines for physical activity (150 mins/wk)

Behavioral Modification/therapy

Weight loss meds are not indicated during pregnancy, or lactation

pediatrics – Orlistat is approved for use in children 12 and older

Herbal Supplements

are not recommended as part of a weight loss program. They have

unpredictable amounts of active ingredients and unpredictable – and potentially harmful – side effects.”

www.NHLBI.NIH.gov

References Adult Obesity Facts. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/adult.html

Apovain CM, Aronne LJ, Bessesen DT, et al. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2015:100(2):342-362. doi:10.1210/jc.2014-3415.

Boyer EW. Serotonin Syndrome (Serotonin Toxicity). UpToDate. https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity. Last updated Aug 5, 2016. Accessed Jan 3, 2018.

Bray GA. Obesity in Adults: Drug Therapy. UpToDate. https:www.uptodate.com/contents/obesity-in-adults-drug-therapy. Updated Mar 25, 2016. Accessed Feb 9 2017.

Bray GA. Obesity in Adults: Prevalence, Screening, and Evaluation. UpToDate. https://www.uptodate.com/contents/obesity-in-adults-prevalence-screening-and-evaluation. Updated Jan 31, 2017. Accessed Jan 9, 2018.

Hamby O. Obesity Medication. Medscape. https://emedicine.medscpare.com/article/123702-medication. Updated Mar2, 2017. Accessed Sept 29, 2017.

Hahipah ZN, Nasr EC, Bucak, E, et al. Efficacy of Adjuvant Weight Loss Medication After Bariatric Surgery. American Society for Metabolic and Bariatric Surgery. 2018; 93-98. doi.org/10.1016/j.soard.207.10.02.

Khan S, Horn DB, Still C. Insights into the Patient Population with Obesity. Bariatric Times. 2016; 13: Supplement C

Kyle T, Kuehl B. Prescription Medication & Weight Gain – What You Need To Know. Obesity Action Coalition.

Neeland IJ, Poirer P, Depres JP. Cardiovascular and Metabolic Heterogenity of Obesity. Clinical Challenges and Implications for Management. Circulation. 2018; 1391-1406

Obesity. WHO. http//www.who.int/topics/obesityen/. Published 2017

Overweight & Obesity. Centers for Disease Control and Prevention. https//www.cdc.gov/obesity.adult.indexhtml. Published April 27, 2012

Primack, P. What to Expect from New Chronic Weight Management Medications.

Prescription Medications to Treat Overweight and Obesity. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/weight-managemnt/prescription-medication.

Rucker D, Padwal R, Li SK, et al. Long Term Pharmacotherapy for Obesity and Overweight: Updated Meta-analysis. BMJ. September 2007

Skversky R. Medical Weight-Loss: Dispelling the Myths.

State of Obesity in Delaware. State of Obesity.Org. https://stateof obesity.org/states/de

Yanovski SZ, Yanoski JA. Long-term Drug Treatment for Obesity. JAMA. 2014:311 (1):74-86. doi10.1001/jama.2013.281364.