1. Multidisciplinary Management of Overweight, and Obesity An Update for Primary Care Providers
Jonathan Stoehr, MD PhD
Endocrinology, Diabetes and Metabolism
Virginia Mason Medical Center
Seattle, WA

2. Speaker’s Disclosure
There is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

3. Objectives
Briefly review the epidemiology of the obesity epidemic overall, and within our health system.
Review recent clinical practice guidelines on overweight / obesity
Review medical strategies for helping prevent weight gain, and promoting weight loss.

4. A significant threat to our health, life expectancy, and economy
Obesity recently passed cigarette smoking as the leading source of Quality-Adjusted Life Years lost in the USA.
Am J Prev Med Feb;38(2):138-44
Obesity associated with $1,400 per year increase in direct medical costs per patient. Diabetes: $6,600 per year (per patient).
CDC Data, Thomas Frieden
Direct medical costs associated with overweight/obesity $113.9 billion in 2008.
Obes Rev Jan;12(1):50-61

5. Obesity is Prevalent among Patients presenting with common complaints.
19% 8%
11%
= Normal Weight (BMI <25)
= Overweight (BMI 25-30)
= Obesity I (BMI 30-35)
21%
16%
= Obesity II (BMI 35-40)
= Obesity III (BMI >40)
Woodward S and Stoehr JP. Internal review of all patient medical visits to Virginia Mason Medical Center, q1 2014

6. Is a 5% weight reduction clinically meaningful for patients?

7. Established Health Benefits of 5% Weight Reduction
Prevention of Diabetes
Knowler WC et al. NEJM :394
Improved Glycemic Control in patients with Type 2 Diabetes
Wycherley et al. J Diab Obes Met, 2008.
Improvement in Sleep-Disordered Breathing
Peppard PE et al. JAMA :3015
Foster et al. Arch Int Med :1619.
Improved Blood Pressure, Cholesterol / Lipids
Van Gaal LF et al. Eur Heart J Suppl :L21-26
Improved joint pain / stiffness and function, in Osteoarthritis
Felson DT. J Rheumatol :7.
Christensen et al. Osteoarthritis and Cartilage (1):20-27
Improved HR-QOL
Blaine BE et al. J Health Psychology :66
Improved Reproductive Function, Fertility
Pasquali R et al. Human Reprod :359
US Surgeon General, Institutes of Medicine, NHLBI, NIDDK, Centers for Disease Control and Prevention

8. Food…For Thought
1 in 3 Americans born in the year 2000 will develop diabetes sometime in their life.
Narayan et al, JAMA, 2003
Among overweight adults, losing as little as 5-7% of a person’s total weight reduces risk of developing type 2 diabetes by 60%.
Diabetes Prevention Program. Diabetes Care 29(9), 2006

9. Clinical Practice Guidelines AHA / ACC / The Obesity Society
Measure BMI, Waist Circumference Annually
For ALL Patients with BMI > 30 or BMI >27 + Cardiovascular Risk Factors
Advise modest (5-10%) weight loss
Assess Motivation to Change
Prescribe Kcal/day reduction
(approximately 1 pound per week)
Comprehensive Lifestyle Change Program

10. How to help patients achieve weight loss?

11. Consider that Weight Gain may be an Adverse Effect of Medications
Anti-diabetes Agents
Psychiatric Meds
Insulin
Dopamine Antagonists
Glipizide, Glyburide
Atypical Antipsychotics
Pioglitazone
Tricyclics
Corticosteroids
Lithium
Prednisone
Anticonvulsants
Dexamethasone
Valproic Acid
Inhaled / Articular
Carbamazepine
Hormones
Gabapentin
Estrogen
Progestins
Antihypertensives
Beta Blockers

12. Treatment of Peptic Ulcer Disease, ca 1970
Lifestyle Modification
Essentially no change
Progressive disease
Medical Therapy
Modest improvement
Surgical Therapy
Significant improvement
Chance for cure

13. Total Body Energy (mass)
1970s approach to the Obese Patient: Obesity as a disorder of personality.
Energy Intake (Consumption)
Obesity caused by lack of self control (over-consumption), laziness (sedentary lifestyle), poor impulse control (cravings).
Total Body Energy (mass)
Pejorative.
Harms Dr–Pt relationship.
No clinical utility.
Energy Expenditure (Heat, Work)

14. 2015 approach to the Obese Patient: Understanding Altered Physiology.
Energy Intake (Consumption)
Food intake and energy expenditure are NOT totally under voluntary control, but reflect the effects of a neural network control system that measures and regulates body composition.
Total Body Energy (mass)
Energy Expenditure (Heat, Work)

15. Afferent pathways for sensation of adiposity and satiety.

16. Strategy: Consider FDA-Approved Anti-Obesity Agents
Phentermine / Topiramate (Qsymia®)
Lorcaserin (Belviq®)
Bupropion / Naltrexone (Contrave®)
Liraglutide (Saxenda®, Victoza®)
Orlistat (Xenical®, Alli®)
Stimulant Appetite Suppressants
Phentermine
Diethylpropion

17. Other Anti-Obesity Agents that I would never prescribe

18. Phentermine / Topiramate (Qsymia®) for Obesity
Phase III Studies:
EQUIP:
1,267 patients, 12 months
Completers lost 14.7% (37#)
CONQUER:
2,487 patients, 12 months
Completers lost 13.2% (30#)
SEQUEL:
676 patients, 24 months
Phase II Studies:
EQUATE: 756 patients, 6 months
OB-201: 200 patients, 6 months
DM-230: 130 patients, 12 months

19. Phentermine / Topiramate (Qsymia®) for Obesity
Improvements:
Waist Circ. (-9.2cm)
Systolic BP (-5.6mmHg)
Diastolic BP (-3.8mmHg)
Cholesterol (-6.3mg/dL)
LDLc (-6.9mg/dL)
HDLc (+6.8mg/dL)
TG (-10.3mg/dL)
Insulin, HOMA-IR, Adiponectin, hs-CRP
No Change:
fasting glucose, A1c
Phentermine ADRs:
Dry Mouth (13%-21%)
Insomnia (6%-10%)
Dizziness (7%-10%)
Headache (7%-10%)
Anxiety (2%-4%)
Irritability (3%)
Topiramate ADRs:
Paresthesia (14%-21%)
Constipation (15%-17%)
Dysgeusia (7%-10%)
Inattention (2%-4%)

20. Lorcaserin (Belviq®) for Obesity
Phase III Studies:
BLOOM:
3,182 patients, 2 years
Completers lost 6%
BLOSSOM:
4,008 patients, 12 months

21. Lorcaserin (Belviq®) for Obesity
Modest Improvements
Body Mass Index
Waist Circumference
Systolic & Diastolic BP
Triglycerides
Fasting Glucose
Fasting Insulin
HOMA-IR
Hemoglobin A1c
Hs-CRP
IWQOL-Lite Score

22. Bupropion / Naltrexone (Contrave®) for Obesity
Phase III Studies:
COR-I:
1,742 patients, 56 weeks
Completers lost 8%
COR-II:
1,496 patients, 56 weeks

23. Liraglutide (Saxenda®, Victoza®) for Obesity
56-week double-blind placebo-controlled RCT
Improvements in:
Weight, BMI, Waist Circ
LDL, TG, HDL, Insulin
Adverse Effects:
nausea, vomiting, dyspepsia, headache, constipation, diarrhea, injection site hematoma.
cholelithiasis, cholecystitis.
pancreatitis (majority gallstone-related).
NEJM. 373(1), p

24. When to Consider Obesity Pharmacotherapy
Indications
BMI > 30
BMI > 27 PLUS Comorbidity:
Diabetes, OSA, NAFLD, DJD, Dyslipidemia
BMI
High surgical risk.
Medical Rx as Bridge to Surgery
Substantial weight loss needed and low surgical risk.
Initial Surgery
Modest weight loss needed.
Initial Medical Rx

25. Summary
New Clinical Practice Guidelines emphasize counseling all overweight / obese patients about the health benefits of modest weight loss.
Emerging medical treatments for obesity are directed at the neural network that senses and regulates body composition.
Multiple new drug classes are FDA approved, with large-scale clinical trial data showing sustained, clinically meaningful weight reduction.
Phentermine / Topiramate (Qsymia®)
5-HT2b Agonist Lorcaserin (Belviq®)
Bupropion / Naltrexone (Contrave®)
Liraglutide (Saxenda®, Victoza®)

26. Acknowledgements OHSU University of Wisconsin, Madison
Jonathan Purnell, MD
Bart Duell, MD
Robert Klein, MD
University of Wisconsin, Madison
Alan Attie, PhD
Yale University School of Medicine
Chris Ruser, MD