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Overview of the Pharmacologic  & Surgical Treatment for 

Obesity 

Christopher D. Still, DO, FACN, FACP. FTOSMedical Director, Center for Nutrition & Weight Management

Director,  Geisinger Obesity Research Institute Geisinger Health Care System

Danville, Pennsylvania

May 25, 2018

Diet

Components of an Effective Obesity Management Program

Surgery

or Medications

Physical Activity

Behavior Modification

Wadden TA, Foster GD. Behavioral treatment of obesity. Med Clin North Am. 2000;84:441-461Stumbo, PH, et. al. Dietary and medical therapy of obesity. Surg Clin N Am 85(2005)703-723

Currently Available Treatments: Risks and Efficacy

Lower risk

Higher risk

Lower efficacy Higher efficacy

BPD‐DS

Devices*

Pharma

Diets

VLCD

Lapband Sleeve

Roux‐en‐Y bypass

.

Jensen MD, Ryan DH, et al. J Am Coll Cardiol. 2013;pii:S0735‐1097(13)06030‐0. http://formularyjournal.modernmedicine.com/print/368664. Accessed May 12, 2014.

*Gastric sleeve and vagal stimulator under phase 3 study  

SVLCD: very low calorie diet

.

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DIET

Intake Expenditure

INDIVIDUAL INFLUENCESGenetic/Epigenetic

StableFat

Carb

Protein

ETOH

TEF

BasalMetabolic

Rate

Activity

Metabolism

ETOH = ethyl alcohol; TEF = thermic effect of food

Which Diet is Best?

Low Calorie

Low Fat

Low CHO

Low Glycemic

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What is the Relationship Between Macronutrient Proportion and Body

Weight in Adults?

• There is strong and consistent evidence that when calorie intake is controlled, macronutrient proportion of the diet is NOT related to losing weight

• No optimal macronutrient proportion was identified for enhancing weight loss or weight maintenance

Weight and Metabolic Outcomes After 2 Years on a Low CHO vs Low-Fat Diet

Foster, GD, et al. Ann Intern Med. 2010;153(3):147-157. doi:10.7326/0003-4819-153-3-201008030-00005

Predicted absolute mean change in body weight for participants in the low-fat and low-carbohydrate diet groups, based on a random-effects linear model. Error bars represent 95% CIs.

A Randomized Trial

Meta Analysis: Comparison of Weight Loss Among Diet

Programs in Overweight and Obese Adults

• 48 randomized trials; N=7,286 overweight or obese persons

• 25 of the studies examined weight loss at one year; n=5,000

CONCLUSION• Weight loss differences between individual diets were small

• Any diet a patient will adhere to in order to lose weight is best9

6 Months 12 Months

Low-fat dietsOrnish, Rosemary Conley ~ 60 kcal CHO / 10-15% kcal PRO / ≤20% kcal FAT

7.99 kg 7.27 kg

Low-carb dietsAtkins, South Beach, Zone≤40% kcal CHO / 30% kcal PRO / 30-55% kcal FAT

8.73 kg 7.25 kg

Johnston BC, et a. JAMA. 2014;312(9):923-933.

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Effects of Low-Carbohydrate and Low-Fat Diets

• n= 60/82; low-fat group <30% fat daily (<7% sat fat) 55% from carbs

• n=59/79; low-carb group <40 gm/day

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Randomized trial, 119 completers, 12 months

Conclusion:Low‐carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low‐fat diet

−1.8 kg

−5.3 kg

−3.5 kgP=0.002

−0.44P=0.002

-0.49

-0.05

Total HDL Cholesterol Ratio

−1.5%P=0.011

0.3

-1.2

% Fat Mass

−0.16 mmol/L (−14.1 mg/dL)

P=0.038

-0.07

-0.23

Triglyceride Level

Bazzano LA, et al. Ann Intern Med. 2014;161(5):309-318. *P< 0.05 for between-group difference

• 8 calories per pound for women, no correction for exercise• 250 lb. women = ~2000 kcal/day upon presentation

• Recommend 1500 kcal/day meal plan

• 10 calories per pound for men, no correction for exercise• 300 lb. man = ~3000 kcal/day upon presentation

• Recommend 2500 kcal meal plan

Rule of Thumb for Calculating Current Caloric Needs

Most Popular Commercial Programs With an Evidence Base to Evaluate

Weight Watchers

Two diet options, expanded from classic points program

Low cost (as little as $12 per week)

Choose between web-based and group setting

Lay counseling

Nutrisystem

Provides food and telephone counseling

~$280-$370 per month

Shelf-stable dry or frozen foods with supplemental fruits and vegetables

Jenny Craig

Provides food and in-person or telephone counseling

~$500-$650 per month

Shelf-stable dry or frozen foods with supplemental fruits and vegetables

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Online Programs

INTERNET-DELIVERED PROGRAMS

Most successful internet programs, that provide weekly email feedback to participants, will induce weight losses of ~ 2/3 the size of those achieved by traditional on-site behavioral programs

14Wadden TA, et al. Circulation. 2012;125(9):1157-70.

Bottom-line on Diets

• Reduce Calories by ~ 500 kcal/day

• Stick with it!!

• Goal weight loss: 5-10% Increments goals

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Deterioration Lipid profile Improvement

Impaired Insulin sensitivityBlood insulinBlood glucose

Improved

Risk markers for thrombosis

Inflammatory markers

Impaired Endothelial function

Improved

Increased Risk Low

10% Weight Loss= 30% VAT Loss

Abdominal obesityIncreased waistcircumference

After weight lossReduced waist circumference

VisceralAdipose Tissue

VAT

VisceralAdipose Tissue

VAT

Subcutaneous Adipose Tissue Subcutaneous Adipose Tissue

Visceral Adipose Tissue: Associated with Cardiometabolic Risk

Adapted from: Després J, et al. BMJ. 2001;322:716-720.

The Power of Monitoring and Accountability

Self-monitoring Frequent Weigh-Ins

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Water Intake

AVOIDANCE OF

• Regular sodas

• Fruit juices

• Caloric beverages

Activity

Intake Expenditure

INDIVIDUAL INFLUENCESGenetic/Epigenetic

StableFat

Carb

Protein

ETOH

TEF

BasalMetabolic

Rate

Activity

Metabolism

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The Lifestyle Approach

0

2

4

6

8

10

0 2 4 6 8 10 12 14 16 18 20 22 24

Noon-time jog

Walk to bus stop

After-dinner walk

Time (hours)

Sedentary

ExerciseLifestyle Activity

Blair SN, et al. Med Exerc Nutr Health. 1992;1:54-57.

Tracking Physical Activity

JawBone AccelerometerNike FUEL

Fitbug FitbitBodyMedia

PHARMACOTHERAPY

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Criteria for Using FDA Approved Medications

BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40

www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/

Underweight Normal Overweight Obesity I Obesity II Obesity III

BMI>27 kg/m2

with ≥1 comorbidity

BMI>30 kg/m2

with no comorbidities

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FDA‐Approved Pharmacotherapy Options for the Treatment of Obesity

• Phentermine (and other noradrenergic agents)

• Orlistat (Xenical/Alli)

• Phentermine/topiramate ER (Qsymia)

• Lorcaserin (Belviq)

• Bupropion SR/Naltrexone SR (Contrave) 

• Liraglutide 3.0mg (Saxenda) 

Phentermine

• Sympathomimetic amine, NE release

• Blunts appetite

• Approved in 1959 for short‐term use, schedule IV

• Dosing: 8‐37.5 mg qAM; use lowest effective dose

• Contraindications: pregnancy, nursing, MAOIs, glaucoma, drug abuse history, hyperthyroidism

• Relative contraindications: uncontrolled HTN, tachycardia, history of CAD, CHF, stroke, arrhythmia 

Phentermine [package insert]. Cranford, NJ: Alpex Pharma SA : 2011. Munro JF, et al. Br Med J. 1968;1(5588):352‐354.

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Lorcaserin

• Selective 5HT‐2c receptor agonist; stimulates α‐MSH 

production from POMC neurons, activating MC4R

• Increases satiety

• Approved in 2012 for long‐term use, schedule IV

• Single dose: 20 mg XR qday; discontinue if less than 5% weight 

loss after 12 weeks of use

• Contraindications: pregnancy

• Warnings: co‐administration with serotonergic or 

antidopaminergic agents, valvular heart disease, psychiatric 

disorders (euphoria, suicidal thoughts, depression), priapism, 

risk of hypoglycemia with some diabetes medications

BELVIQ [Prescribing Information]. Woodcliff Lake, NJ: Eisai Inc; 2012. 

• Phentermine: sympathomimetic amine; blunts appetite

• Topiramate: increases GABA activity, carbonic anhydrase inhibitor, other actions; prolongs satiety

• Approved in 2012 for long‐term use; schedule IV

• Treatment (“recommended” dose): 7.5/46 mg qAM; max dose: 15/92 mg

• Contraindications: pregnancy, glaucoma, MAOIs, hyperthyroidism

• Warnings: fetal toxicity, increased HR, suicidal thoughts, mood disorders, sleep disorders, cognitive impairment, metabolic acidosis, creatinine elevations, hypoglycemia with some diabetic medications

Phentermine and topiramate extended-release [package insert]. Mountain View, CA : Vivus; 2012.

Phentermine/Topiramate ER

Bupropion SR/Naltrexone SR

• Approved by FDA September 10, 2014• Bupropion: dopamine/noradrenaline reuptake inhibitor; 

activates POMC neurons in the hypothalamus, leading to decreased appetite

• Naltrexone: opioid receptor antagonist; blocks autoinhibition of POMC neurons and amplifies the effect of bupropion

• Dosing:– Week 1:  1 tab (8mg/90mg) in AM– Week 2:  1 tab BID– Week 3:  2 tabs in AM; 1 in PM– Week 4+:  2 tabs BID

• Consider discontinuation if <5% weight loss after 12 weeks

Greenway, et al. Obesity. 2009;17:30‐39. 

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Liraglutide 3.0 mg

• Glucagon‐like peptide 1 (GLP‐1) receptor agonist

• Multiple actions; effect on weight is primarily via POMC neurons

• FDA‐approved 3.0 mg/day for primary indication of obesity

Baggio LL, et al. J Clin Invest. 2014;24(10):4223‐4226; Secher A, et al. J Ciin Invest. 2014;124(10):4473‐4488.

Choosing Between Options

0%

25%

50%

75%

100%

>5% BWL

>10% BWL

Contraindications & Cautions

Clinical scenario Avoid/caution

Elevated seizure risk Naltrexone SR/bupropion SR 

h/o recurrent kidney stones Phentermine/Topiramate ER, orlistat

h/o glaucoma Phentermine/Topiramate ER

Uncontrolled hypertension Naltrexone SR/bupropion SR 

Coronary artery disease Phentermine

Moderate‐severe renal impairment

Do not exceed half‐dose: Phentermine/Topiramate ER, Naltrexone SR/bupropion SR Caution: liraglutide 3.0 mg, lorcaserin

Moderate‐severe hepatic impairment

Do not exceed half‐dose: Phentermine/Topiramate ER Do not exceed ¼ dose: Naltrexone SR/bupropion SR Caution: liraglutide 3.0 mg, lorcaserin

SSRI use Caution: lorcaserin

See package inserts

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Dual Benefits

Obesity and… Consider, but not explicitly approved…

Smoking Naltrexone SR/bupropion SR 

Depression Naltrexone SR/bupropion SR 

Migraines Phentermine/Topiramate ER

Diabetes Liraglutide 3.0 mg

Chronic constipation Orlistat 

Elevated LDL Orlistat

Slide courtesy of S. Kahan

Thoughts on Pharmacotherapy

• Treatment of obesity with pharmacotherapy as an adjunct to lifestyle modification is a valuable option for obesity treatment

• Several options are available and FDA approved

• Understand potential benefits and risks of agents when planning treatment

• Different patients respond to different medications

• If one option doesn’t work well, consider others

• REALISTIC EXPECTATIONS

Bariatric Surgery Criteria

With ≥1 severe

obesity-associated comorbidity

(e.g., diabetes or OSA)

With no comorbidities

BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40

www.cdc.gov/healthyweight/assessing/bmi/adult_bmi

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Sleeve Gastrectomy

Madsbad S, Dirksen C, Holst JJ. Lancet Diabetes Endocrinol. 2014; 2:152–64.

Most Common Bariatric Procedures

Biliopancreatic Diversion with

Switch

Roux-en-Y Gastric Bypass

37

260,000 procedures annually, 95% laparoscopic

Sleeve Gastrectomy

38|

Bariatric procedure originally as part of BPDDS, now used as a first stage or stand alone if patient loses enough weight

Remove part of stomach, creating a sleeve from esophagus to antrum

A 36Fr bougie is used to size the sleeve

Now a covered benefit in US -- CMS

Roux-en-Y gastric bypass (RYGB)

Ghrelin

GLP-1

PYY

Insulin

Excess Weight Loss is ~65-70%*

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Duodenal Switch

Combination Operation Sleeve Biliopancreatic Diversion Neurohormonal – decreased

Ghrelin and increased GLP1

Highest Remission rate for Type 2 Diabetes

Excess Weight Loss is ~85%

Significant risk of malabsorption of nutrients

Usually performed on patients with a BMI>60kg/m2

STAMPEDE TrialSurgical Therapy And Medications Potentially Eradicate Diabetes Efficiently

50Intensive Medical

Therapy Alone

50Intensive Medical

Therapy Alone

• A1c >7.0%• BMI: 27-43 kg/m2

• Age: 20-60 years218 Patients Screened

50 Medical Therapy +

Sleeve Gastrectomy

Year 3 Population40 48 49

150 Randomized

50Medical Therapy +

Gastric Bypass1 withdrew consent prior to surgery8 withdrew consent

2 lost to follow-up2 lost to follow-up

91% RetentionKashyap SR, et al. Diabetes Obes Metab. 2010;12:452-454.

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STAMPEDE Trial: Change in A1cC

han

ge

in A

1c (

%)

0.0

-0.5

-1.0

-1.5

-2.0

-2.5

-3.0

-3.50 3 6 12 24 36

0.0

-0.5

-1.0

-1.5

-2.0

-2.5

-3.0

-3.50 3 6 12 24 36

P <0.001

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 9.0 (8.5) 7.1 (6.8) 7.5 (6.9) 7.7 (7.3) 8.4 (7.6)Gastric Bypass 9.3 (9.2) 6.3 (6.2) 6.3 (6.1) 6.5 (6.4) 6.7 (6.6)Sleeve 9.5 (8.9) 6.7 (6.4) 6.6 (6.4) 6.8 (6.8) 7.0 (6.6)

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 9.0 (8.5) 7.1 (6.8) 7.5 (6.9) 7.7 (7.3) 8.4 (7.6)Gastric Bypass 9.3 (9.2) 6.3 (6.2) 6.3 (6.1) 6.5 (6.4) 6.7 (6.6)Sleeve 9.5 (8.9) 6.7 (6.4) 6.6 (6.4) 6.8 (6.8) 7.0 (6.6)

MedicalMedical

Sleeve Sleeve

Gastric BypassGastric Bypass

Kashyap SR, et al. Diabetes Obes Metab. 2010;12:452-454.

P <0.001

-12.0

-10.0

-8.0

-6.0

-4.0

-2.0

0.0

-12.0

-10.0

-8.0

-6.0

-4.0

-2.0

0.0

90 3 6 12 24 360 3 6 12 24 369

STAMPEDE Trial: Change in BMI

Ch

ang

e in

BM

I (kg

/m2)

P <0.001

P <0.001

MedicalMedical

Sleeve Sleeve

Gastric BypassGastric Bypass

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 36.4 34.6 34.2 35.0 34.8Gastric Bypass 37.1 28.2 26.7 27.3 27.9Sleeve 36.1 28.3 27.1 27.9 29.2

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 36.4 34.6 34.2 35.0 34.8Gastric Bypass 37.1 28.2 26.7 27.3 27.9Sleeve 36.1 28.3 27.1 27.9 29.2

P=0.006

Kashyap SR, et al. Diabetes Obes Metab. 2010;12:452-454.

Five-year data of patients with T2DM and BMI of 27 to 43

-5.3 kg

-18.6 kg

Medical Therapy

Sleeve Gastrectomy

Gastric Bypass -23.2 kg

Schauer PR, et al. N Engl J Med. 2017 Feb 16;376(7):641-651.

Mean BMI Value at Visit

Weight Change After Bypass and Sleeve vs Medical Tx In Patients with Type 2 DM

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Five-year Outcomes for Bariatric Surgery vs. Intensive Medical Therapy for Diabetes

Schauer PR, et al. N Engl J Med. 2017 Feb 16;376(7):641-651.

Routine Vitamin and Mineral Supplementation for RYGB Patients

Supplement

• Multivitamin-mineral / Prenatal

• Calcium citrate w/ vitamin D

• Elemental iron

• Vitamin B12

Dosage

• 1 to 2 daily

• 1200 to 2000 mg/day + 3000 U/day Vitamin D

• 40 to 65 mg/day

• 5000 ug/day orally OR 1000 ug/mo IM OR 500 ugweekly intranasal

RYGB = Roux-en-Y gastric bypass.

Bariatric Surgery ‐ Low Mortality

0.13%

0.52%

0.93%

3.30%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

Bariatric Surgery Lap Chole Hip Replacement CABG

Mortality Rate (%)

29 30 31 32

When performed at a Bariatric Surgery Center of Excellence

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Reduction of Premature Death

0.68%

6.17%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

8.0%

9.0%

10.0%

Bariatric* Controls

MO

RT

ALI

TY

89% Reduction in Risk of Death Over 5 Years

* Includes perioperative (30‐day) mortality of 0.4%P= 0.001

Currently Available Treatments: Risks and Efficacy

Lower risk

Higher risk

Lower efficacy Higher efficacy

BPD‐DS

Devices*

Pharma

Diets

VLCD

Lapband Sleeve

Roux‐en‐Y bypass

.

Jensen MD, Ryan DH, et al. J Am Coll Cardiol. 2013;pii:S0735‐1097(13)06030‐0. http://formularyjournal.modernmedicine.com/print/368664. Accessed May 12, 2014.

*Gastric sleeve and vagal stimulator under phase 3 study  

SVLCD: very low calorie diet

.