The Obesity Epidemic Linda Davis, MD - Director and Founder Kolvita Family Medical Group - Primary Care Network
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The Obesity Epidemic
Linda Davis, MD
Director and Founder
Kolvita Family Medical Group
Mission Viejo, CA
Learning Objectives ▪ Discuss the health impact related to obesity and its associated disease risks ▪ Explain what qualifies as “meaningful” weight loss and its impact on your patients ▪ Review the FDA approved medications to help manage obesity
Why Do We Care About Obesity?
Global Epidemic
▪ 2016 – 1.9 billion adults worldwide were overweight and
650 million of these were obese
▪ 2017 – 4 million deaths associated with being overweight
or obese (GBD)
▪ Prevalence of obesity in children and adolescents
(ages 5-19) increased >4x from 1975-2016 (4% to 18%)
GBD = Global Burden of Disease
https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight Accessed April 23, 2021
GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational,
and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.
The Lancet. 8 Nov 2018;392:1923-94.
Health Impact of Obesity
in the United States
▪ Obesity in mid-life shortens life
expectancy by 4-7 years
▪ Medical spending increased in obesity
(2005 values)
▪ Men +$1152/year
▪ Women $3613/year
▪ Obesity medical costs in US $190 Billion,
21% of healthcare expenditures
Peeters A et al. Ann Intern Med. 2003;138:24-32. Cawley J, Meyerhoefer C. J Health Econ. 2012;31:219-230.
Prevalence† of Self-Reported Obesity Among US 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
Prevalence† of Self-Reported Obesity Among US Adults by State and Territory, BRFSS, 2019 †Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011. *Sample size
Prevalence of Self-Reported Obesity Among Hispanic Adults, by State and Territory, BRFSS, 2017-2019 *Sample size
Prevalence of Self-Reported Obesity Among Non-Hispanic Black Adults, by State and Territory, BRFSS, 2017-2019 *Sample size
Obesity and COVID-19
▪ Risk factor for complicated COVID-19 infection
▪ Chronic inflammation resulting in disruption of immune and
thrombogenic responses to pathogens
▪ Impaired lung function due to excess weight
▪ Increased risk for mechanical ventilation (both overweight and
obese patients)
▪ Increased risk for hospitalization and death (especially in
thoseObesity and COVID-19 (cont.)
Estimated risk for severe COVID-19 associated illness among adults
aged ≥18 years, by body mass index (BMI) and age group
IMV = invasive mechanical ventilation
Kompaniyets L, Goodman AB, Belay B, et al. Body Mass Index and Risk for COVID-19–Related Hospitalization, Intensive Care Unit Admission, Invasive
Mechanical Ventilation, and Death — United States, March–December 2020. MMWR Morb Mortal Wkly Rep 2021;70:355–361.What is Obesity?
▪ A state of excess adipose tissue mass (Harrison’s:
21st edition)
▪ A chronic, relapsing, multifactorial, neurobehavioral
disease, wherein an increase in body fat promotes
adipose tissue dysfunction and abnormal fat mass
physical forces, resulting in adverse metabolic,
biomechanical, and psychosocial health
consequences (Obesity Medicine Association)
https://obesitymedicine.org/definition-of-obesity/ Accessed April 18, 2021Methods for Identifying Obesity
▪ Body Mass Index (BMI)
▪ Pros: easy to calculate [weight (kg)/height (m2)], low cost, reproducible
▪ Cons: doesn’t account for gender, muscle mass, ethnicity and frame size
Underweight: ≤ 18.5 kg/m²
Normal weight: 18.5-24.9 kg/m²
Overweight: 25.0-29.9 kg/m²
Class I Obesity: 30.0-34.9 kg/m²
Class II Obesity: 35.0-39.9 kg/m²
Class III Obesity: ≥ 40.0 kg/m²
https://obesitymedicine.org/definition-of-obesity/ Accessed April 23, 2021Methods for Identifying Obesity
▪ Abdominal (aka “waist”) Circumference: measurement of
central adiposity and it is associated with metabolic disease risk
▪ Pros: easy to perform, low cost
▪ Cons: variability in technique, different reference ranges based on
gender and ethnicity
Caucasian Males: ≥ 40 inches correlates with obesity
Caucasian Females: ≥ 35 inches correlates with obesity
Asian Males: ≥ 35 inches correlates with obesity
Asian Females: ≥ 31 inches correlates with obesity
https://obesitymedicine.org/definition-of-obesity/ Accessed April 26, 2021Methods for Identifying Obesity
▪ % Body Fat: most accurate method of assessing adiposity
▪ Pros: accounts for differences in age, gender, body frame size, and muscle mass
▪ Cons: cost, limited access, doesn’t assess for metabolic disease
▪ Dexa scanning
▪ Air or water displacement
▪ 4-point or 2-point bioimpedance
▪ Skin calipers
Males: Obesity ≥ 25% body fat
Females: Obesity ≥ 32% body fat
https://obesitymedicine.org/definition-of-obesity/ Accessed April 26, 2021Pressures Sedentary
Body to Be
Workplaces/Schools/
Entertainment
Weight Less Activity “Unfriendly”
Physically Community Design
Biology Active Drive-Through
Conveniences
Elevators/Escalators
Remote Controls
Labor-Saving Devices
Television/Computer
Ein Eout
Behavior
Pressures Portion Sizes Soft Drinks/Junk Food Variety
to Eat High Energy Density in Schools Convenience
High Glycemic Index Added Sugar Great Taste
More
Low-Cost Easy Food Access Ads/MarketingThe Biology Behind Eating
▪ Central Nervous System
▪ Homeostatic system: hunger and satiety
▪ Reward system: over-rides to produce food intake even in absence
of hunger
▪ Peripheral Signals
▪ Leptin from fat
▪ GLP-1, GIP, PYY, OXM, from small intestine
▪ Pancreatic polypeptide, amylin, insulin from pancreas
▪ Ghrelin from stomach
GLP-1 = Glucogen-like peptide 1; GIP = Gastric inhibitory polypeptide;
PYY = Peptide YY; OXM = oxyntomodulinRisk of Associated Disease
According to BMI and Waist Size
Waist ≤ Waist >
Weight 40” in men or 40” in men or
BMI
Classification 35” in women 35” in women
18.5 or less Underweight -- N/A
18.5 - 24.9 Normal -- N/A
25.0 - 29.9 Overweight Increased High
30.0 - 34.9 Obese High Very High
35.0 - 39.9 Obese Very High Very High
40 or greater Extremely Obese Extremely High Extremely HighAbdominal Fat Distribution Increases
the Risk of Coronary Heart Disease
The Iowa Women’s Health Study
2.5
Relative Risk
2.0
1.5
1.0
0.5
0.0
3 2 1
Body Mass Index Tertile
Folsom AR, et al. Arch Intern Med. 2000;160:2117-2128.A normal waist to hip ratio
>0.95 for men and 0.86 for women
“Apple” vs. “Pear”
Android=Abdominal= Gynecoid=Peripheral=
Central=Apple shaped Pear shaped
Above the
waist
Below
the waistObesity-Related Health Problems
Metabolic effects
▪ Endocrine: Prediabetes and type 2 diabetes, dyslipidemia (low HDL and high triglycerides)
▪ Cardiovascular: HT, CAD, stroke, CHF, AF, venous stasis, DVT, PE
▪ Cancer: Multiple types, most commonly colorectal, postmenopausal breast, and endometrial
▪ Gastrointestinal: GERD, cholelithiasis, nonalcoholic fatty liver disease, nonalcoholic
steatohepatitis
▪ Renal: Nephrolithiasis, proteinuria, chronic kidney disease
▪ Genitourinary:
▪ In women, urinary stress incontinence, polycystic ovarian syndrome, infertility, pregnancy
complications
▪ In men, benign prostatic hypertrophy, erectile dysfunction
▪ Neurologic: Migraine, pseudotumor cerebri
▪ Infections: Greater severity of influenza with severe obesity, skin and soft tissue infections
March 5, 2019. Annals of Internal Medicine In the Clinic ITC35.Obesity-Related Health Problems
Mechanical Effects
▪ Pulmonary: OSA, pulmonary hypertension, restrictive lung
disease, chronic hypoxemic respiratory failure
▪ Musculoskeletal: osteoarthritis, low back pain
Psychosocial Effects
▪ Depression and anxiety
▪ Social stigmatization
March 5, 2019. Annals of Internal Medicine In the Clinic ITC35.Evaluate for Weight Related
Complications at each visit
2013 AHA/ACC/TOS
Guidelines and ACE Guidelines Being overweight can lead
▪ Measure obesity-associated to high blood pressure and
health risks
related complications
▪ Glucose, A1c
▪ Stroke
▪ Blood pressure
▪ Blood vessel damage
▪ Lipids (arteriosclerosis)
▪ Biomechanical problems, joint pain ▪ Heart attack or heart failure
▪ Sleep apnea ▪ Kidney failure
▪ Depression
▪ Cancer history
AHA, American Heart Association
ACC, American College of Cardiology
Jensen MD, et al. 2013 AHA/ACC/TOS Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023. TOS, The Obesity SocietyEvaluate and Measure Weight–
related Health Risk in Patients
2013 AHA/ACC/TOS Guidelines
▪ Screen all patients with BMI at least annually and more
frequently, depending on risk factors
▪ Use waist circumference measure
as a risk factor
▪ Identify high risk patients who need
to lose weight
▪ BMI ≥30 kg/m2
▪ BMI ≥25 kg/m2 with at least one risk factor
▪ ↑ waist circumference (≥40 inches in men,
≥35 inches in women)
Jensen MD, et al. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023.Case Study - Sarah
▪ 44-year-old female 5’2” and 199 lbs with BMI of
36 and 36” waist with hyperlipidemia (total
cholesterol 220, LDL 154), fatty liver (AST 45,
ALT 48) and prediabetes (Hgb A1c 6.2%)
▪ Sedentary lifestyle as medical receptionist with
no exercise
▪ Wants help losing weight
How do you approach this patient
and where do you start?Meaningful Weight Loss is Goal
-3.0% Improvements in glycemic parameters,
reduction of risk for developing diabetes
Greater improvements in glycemic parameters;
-5.0% improvement in blood pressure, HDL, and triglycerides
Improve markers of NAFLD
Urinary incontinence improves
-10.0% Greater improvements in above parameters
Improve symptoms of sleep apnea
-15.0% Even greater improvements in above parameters
NAFLD = Nonalcoholic Fatty Liver Disease
Jensen MD, et al. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023.Counsel Patients on
Lifestyle Modifications
With or without obesity-related CV factors (NIH, AHA, ACCF, ADA)
Patient success linked to provider suggestions!!!
▪ Prescribe a diet
▪ To achieve reduced caloric intake
▪ Refer to professional or evidence-
based program
▪ Increase physical activity
▪ Lifestyle intervention program
NIH, National Institute of Health; AHA, American Heart Association
ACCF, The American College of Cardiology Foundation; ADA, American Diabetes Association
Powell-Wiley TM, et al. Obesity. 2012; 20;849-855.Components of an Effective
Obesity Management Program
Surgery or
Medications
Behavior
Modification
Physical
Diet
Activity
Wadden TA, et al. Med Clin North Am. 2000;84:441-461.
Stumbo, PH, et. al. Surg Clin N Am. 85(2005)703-723.How Much Weight Does the State-of-the-Art
Lifestyle Intervention Produce?
Mean weight loss (%) from baseline by year
Year 0 Year 1 Year 2 Year 3 Year 4
0
-1 -1.01
% Weight change
0.00
-2 -0.63 -0.93 -0.92
-3
-4
-5 -4.66
-6
-5.04
-7
-8 -6.35 P“Diet” vs “Lifestyle Change”
▪ Diets are thought of as temporary – lifestyle changes are long term – “forever”
▪ Reduce caloric intake 500-750 kcal/day – (take into consideration output - if caloric input exceeds
output weight gain will occur)
▪ Commercial programs (eg. Jenny Craig, WW, Nutrisystem) can produce weight loss
▪ Detox/Cleanses/Weight Loss Supplements – Not FDA vetted/approved – often contain some sort
of stimulant (caffeine derivative), effects often short term
▪ With regards to weight loss – no diet has been proven superior to others
▪ With regards to health – specific dietary patterns have good evidence for primary and secondary
prevention of several chronic diseases
▪ Prevention of cardiovascular disease, cancer, type 2 diabetes mellitus, and obesity
▪ Mediterranean diet, the Dietary Approaches to Stop Hypertension diet (DASH), the 2015
Dietary Guidelines for Americans, and the Healthy Eating Plate
Diets for Health Goals and Guidelines: AMY LOCKE, MD, University of Utah Health, Salt Lake City, Utah, JILL SCHNEIDERHAN, MD, University of Michigan
Medical School, Ann Arbor, Michigan, SUZANNA M. ZICK, ND, MPH, University of Michigan School of Public Health, Ann Arbor, Michigan Am Fam
Physician. 2018 Jun 1;97(11):721-728.The Mediterranean Diet ▪ Not a specific diet but rather recommendations based on observations of what people eat that live in the regions surrounding the Mediterranean Sea ▪ The main components of Mediterranean diet include: ▪ Daily consumption of vegetables, fruits, whole grains and healthy fats (ie, olive oil) ▪ Weekly intake of fish, poultry, beans and eggs ▪ Moderate portions of dairy products (Greek yogurt) ▪ Limited intake of red meat ▪ Red wine in moderation (risks vs benefits…)
Intermittent Fasting
▪ Based on timed periods of little/no caloric intake (without reducing vital nutrients)
▪ Triggers the body to shift from utilizing glucose in the liver for energy to ketones
stored in fat - “ketogenesis”
▪ Ketogenesis – reduces oxidative/metabolic stress and promotes/enhances
cellular repair/healing
▪ Short term studies demonstrate improvements in obesity, diabetes,
cardiovascular disease, cancers and neurological disorders. Long term
(longevity outcomes) not known
▪ Examples:
▪ Alternate day fasting, 5:2 intermittent fasting (fasting two days each week)
▪ Daily time-restricted feeding (such as eating only during a six-hour window)
De Cabo R and Mattson MP. Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine. 2019;381(26):2541-2551.
doi: 10.1056/NEJMra1905136.Implementing Intermittent Fasting
Month Time-Restricted Feeding 5:2 Intermittent Fasting
Month 1 10 hour feeding period 5 days/week 1000 calories 1 day/week
Month 2 8 hour feeding period 5 days/week 1000 calories 2 days/week
Month 3 6 hour feeding period 5 days/week 750 calories 2 days/week
Month 4 (goal) 6 hour feeding period 7 days/week 500 calories 2 days/week
De Cabo R and Mattson MP. Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine. 2019;381(26):2541-2551.
doi: 10.1056/NEJMra1905136.Diet Composition Comparison:
Weight Change From Baseline
Protein Fat Carb
0
-0.5
Weight Loss (Kg)
-1
-1.5
-2
-2.5 High Low
-3
-3.5
-4
-4.5 High-low: High-low: High-low:
(P=0.22) (P=0.94) (P=0.42)
-5
Sacks FM, et al. N Engl J Med. 2009;360:859-873.Exercise – Move your body! ▪ The best form of exercise . . . Is the one you will do!! ▪ Exercise can help with weight loss as well as help maintain weight loss ▪ Increases metabolism = more calories burned per day ▪ Increases muscle/lean body mass ▪ Increases insulin sensitivity ▪ Releases endorphins ▪ Combined with diet – more effective for weight loss then either independently
Exercise Recommendations
▪ For General Health
▪ Moderate intensity physical activity or equivalent*
▪ 150 minutes/week
▪ Resistance training
▪ Moderate or high intensity
▪ 2 or more days a week
▪ Weight Loss and Maintenance
▪ 150 to 250 minutes per week moderate intensity
▪ 250 minutes or more per week for maintenance
*Defined as activities that are strenuous enough to burn three to six times as much energy per minute as an individual would burn when sitting quietly,
or 3 to 6 METs (metabolic equivalents). Vigorous-intensity activities burn more than 6 METs.Case Study - Sarah
▪ 44-year-old female with BMI of 36 and 36” waist with hyperlipidemia,
fatty liver, and prediabetes
▪ Sedentary lifestyle as medical receptionist with no exercise
▪ Wants help losing weight
▪ After 6 months with Jenny Craig and walking 2 miles 4 x per week:
▪ 8 lb weight loss now 191 and BMI of 35, waist 35”
▪ Total Cholesterol 202, LDL 138, AST/ALT now normal, hgb A1c 5.9%
She feels frustrated, was hoping for more weight loss.
Additional history: Has 2 children (s/p BTL), told she has gallstones, takes Tramadol
50mg BID for chronic spinal stenosis of lumbar spine.
What is your next step?Efficacy and Safety of
Currently Available Treatments
Meds + VLCD Gastric
Lifestyle1 Lifestyle4 Gastric Band3 Bypass3
0% 5% 10% 15% 20% 25% 30% 35% Weight Loss
Perioperative DVT, thromboembolism or death2
1% for gastric band
5% for bypass
1. Jensen MD, et al., Circulation. 2014;129(25 Suppl 2):S102-138. Weight loss at 3 years3
2. Courcoulas AP, et al. JAMA. 2013;310:2416-2425.
3. LABS consortium. N Engl J Med 2009;361:445-54.
16% for gastric band
4. Colman E, et al. N Engl J Med. 2012;367:1577-1579. 33% for bypass2Meds Don’t Work on Their Own
Important to Use Medication as an Adjunct to Lifestyle Counseling
0
Mean weight loss, kg
2 N=224
4
▪ Sibutramine alone 5.0 ± 7.4
Weight loss (kg)
6
8
▪ Lifestyle-modification alone 6.7 ± 7.9
10 ▪ Sibutramine + brief therapy 7.5 ± 8.0
12
▪ Combined therapy 12.1 ± 9.8
14
16
0 3 6 10 18 40 52
Weeks
Wadden TA, et al. N Engl J Med. 2005;353:2111–2120.Why Do We Need Medication
for Weight Loss?
Address some pathophysiological problems
▪ Adherence to healthy eating plan
▪ Achieve meaningful weight loss
▪ Produce more weight loss –
greater health benefits
▪ Early weight loss = more success
▪ Sustain weight lossWhat Can Weight Loss Medications Do? ▪ Help struggling patients achieve health benefits ▪ Serve as adjunct to lifestyle modifications ▪ Achieve greater meaningful weight loss ▪ Achieve weight loss early to promote long-term success
Pharmacotherapies
Agents Action Approval, Availability
Phentermine • Central noradrenergic agent • Approved, 1959
(Adipex-P) • Schedule II–IV • #1 seller in US
• 3-month prescribing limit
Orlistat • Peripheral pancreatic lipase • Approved, 1999
(Xenical; Alli) inhibitor • Available in US, EU
• Blocks fat absorption
• Available OTC or prescription
• Not scheduled
Kushner RF. Expert Opin Pharmacother. 2008;9:1339-1350.
Phentermine. [prescribing information]. Sellersville, PA: Teva Pharmaceuticals. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/085128s065lbl.pdf
Orlistat [prescribing information]. San Francisco, CA: Genentech;2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020766s026lbl.pdf
Orlistat [package insert]. Moon Township, PA. GlaxoSmithKline, 2011.Pharmacotherapies (cont.)
Agents Action Approval, Availability
Lorcaserin • 5-HT2C serotonin agonist • Approved, summer 2012
(Belviq, Belviq XR) • Little affinity for other • Recalled February 2020 –
serotonergic receptors due to increased cancer risk
(pancreatic, colorectal, and
lung)
Phentermine/ • Sympathomimetic • Approved, summer 2012
Topiramate ER • Anticonvulsant (GABA receptor
(Qsymia) modulation, carbonic anhydrase
inhibition, glutamate antagonism)
Kushner RF. Expert Opin Pharmacother. 2008;9:1339–1350.
Phentermine/topiramate ER [prescribing information]. Mountain View, CA: Vivus Inc.,2012. https://www.qsymiarems.com/full-prescribing-information.pdf
Lorcaserin hydrochloride [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022529lbl.pdfPharmacotherapies (cont.)
Agents Action Approval, Availability
Naltrexone HCl/ • Opioid antagonist • Approved, September 2014
Bupropion HCl • Neuronal reuptake inhibitor of
(Contrave) dopamine and norepinephrine
Liraglutide 3 mg • GLP-1 Receptor agonist • FDA-approved in 2010 for
(Saxenda) • Augments insulin secretion during diabetes (1.8 mg/day)
hyperglycemia, suppresses appetite, • FDA AdCom voted 14-1 in favor of
and delays gastric emptying approval of high-dose (3.0 mg/
day) for obesity on September 11,
2014
• Approved, December 2014
Naltrexone HCl/Bupropion HCl [package insert]. Deerfield, IL; Takeda Pharmaceuticals Intl. Inc. 2014.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf
https://www.ajmc.com/journals/evidence-based-diabetes-management/2015/january-2015/liraglutide-approved-under-new-name-to-treat-obesity
Accessed April 26, 2021Pharmacotherapies (cont.)
Agents Action Approval, Availability
Semaglutide • GLP-1 Receptor agonist • FDA-approved in 2017 for
2.4 mg/week • Augments insulin secretion during diabetes – 0.5 or 1 mg/week
(Wegovy) (Ozempic)
hyperglycemia, suppresses appetite,
and delays gastric emptying • FDA-approved 9/2019 for
diabetes – oral formulation 7
and 14 mg/day (Rybelsus)
• Approved, June 2021 for
weight loss
https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014
Accessed June 7, 2021Phentermine/Topiramate ER ▪ Initially titrate: 3.75/23 mg → 7.5/46 mg ▪ Option to escalate to 15/92 mg with low weight loss response ▪ Contraindications ▪ Pregnancy ▪ Glaucoma ▪ Hyperthyroidism ▪ Monoamine oxidase inhibitors
Effect of Phentermine/Topiramate
Extended Release on Weight Loss in Obese
Adults Over 2 Years: SEQUEL
Weeks 0 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 LOCF
0
–2 -1.8%
–4
LS mean weight loss (%)
–6
–8
-9.3%*
–10
-10.5%*
–12
–14
Placebo PHEN/TPM ER 7.5/46 PHEN/TPM ER 15/92
–16 *pOrlistat
Indications and Dose Contraindications and Warnings
Approved by FDA, 1999 ▪ Contraindications:
▪ Approved in adolescents ▪ Pregnancy, chronic malabsorption
▪ Dosing: syndrome, cholestasis
▪ Rx: 120 mg TID with each meal ▪ Warnings:
▪ OTC: 60 mg TID with each meal ▪ Decrease cyclosporine exposure,
▪ Advise patients: rare cases of severe liver injury,
▪ Nutritionally balanced, reduced- increased levels of urinary oxalate
calorie diet; approximately 30% of ▪ GI AEs: oily spotting, flatus with
calories from fat discharge, fecal urgency, fatty/oily
▪ Take a multivitamin containing fat- stool, oily evacuation, increased
soluble vitamins at bedtime defecation and fecal incontinence
Orlistat [prescribing information]. San Francisco, CA: Genentech;2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020766s026lbl.pdf
Orlistat [package insert]. Moon Township, PA. GlaxoSmithKline, 2011.Naltrexone HCL/Bupropion HCL Use Light Study ▪ Dose escalation required up to ▪ Nearly 9,000 overweight/obese 4-week period patients with CVD risk factors ▪ Bupropion, antidepressant ▪ Rule out excess cardiovascular (Wellbutrin), requires monitoring risk in overweight and obese for worsening and emergence of receiving NB suicidal thoughts ▪ Interim analysis found no ▪ Contraindicated in uncontrolled differences in SBP, DBP, HTN, seizures, chronic opioid Heart rate use, and pregnancy
Naltrexone SR/Bupropion SR
Body Weight Change
Greenway FL, et al for the COR-I Study Group. Lancet. 2010;376(9741):595-605.Liraglutide ▪ Daily injectable ▪ 3 mg dose (1.8 mg used in type 2 diabetes) ▪ Potential risk of medullary thyroid carcinoma (MTC) ▪ Pancreatitis risk ▪ Gallbladder risk ▪ Main side effects: nausea, vomiting
Scale Liraglutide Maintenance Study Wadden TA, et al. Int J Obes (Lond). 2013;37:1443-1451.
Liraglutide with Diet/Exercise at 2 Years
Liraglutide 2.4/3.0, liraglutide 2.4 mg and 3.0 mg pooled
60 Placebo Liraglutide 3.0
Adverse Events, % (n=98) (n=93)
50 Constipation 12.2 18.3
Diarrhea 10.2 15.1
40
Dyspepsia 3.1 8.6
liraglutide
30 Nausea 7.1 48.4
Placebo
Vomiting 2.0 12.9
20
Psychiatric 5.1 12.9
10
0
5% or more 10% or more
Astrup A, et al for the NN8022-1807 Investigators. Int J Obesity. 2012;36:843-854.Reducing Body Weight by % Categories at 1 Year with
Adjunctive Medication Among those who
Complete Treatment*
100
5% weight loss 10% weight loss
90
80
Percentage, %
70
60
50
40
30
20
10
0
Phen/TPM 7.5/46 Phen/TPM 15/92 lorcaserin 10 BID bupropion/naltrexone liraglutide 3.0
32/360
*Combined with lifestyle modification; data are from largest Phase III trialSemaglutide ▪ Weekly injectable ▪ 2.4 mg/week (1 mg/week in T2DM, or oral tablet 7 mg or 14 mg) ▪ Potential risk of medullary thyroid carcinoma (MTC) ▪ Avoid multiple endocrine neoplasia (MEN II) ▪ Not assessed in patients with pancreatitis ▪ Main side effects: GI (i.e., nausea, vomiting, abdominal pain)
STEP Program
(Semaglutide Treatment Effect in People With Obesity)
▪ Included four phase 3 clinical trials testing safety and efficacy in over
4500 adults with overweight or obesity
▪ 68-week trials, 2.4 mg SQ weekly vs placebo
▪ STEP 1 – 1961 adults (NEJM)1
▪ STEP 2 – 1210 adults w/ diabetes (Lancet)2
▪ STEP 3 – 611 adults (also included intensive lifestyle intervention) (JAMA)3
▪ STEP 4 – 803 adults reached 2.4 mg/week target at 20 weeks (weight-loss
observed in the subsequent 48 weeks) (JAMA)4
▪ STEP 1,2, and 4: weight loss ranged from 15%-18% over 68 weeks
1. N Engl J Med 2021; 384:989-1002. DOI:10.1056/NEJMoa2032183
2. The Lancet 2021; https://doi.org/10.1016/S0140-6736(21)00213-0
3. JAMA. 2021;325(14):1403-1413. DOI:10.1001/jama.2021.1831
4. JAMA. 2021;325(14):1414-1425. DOI:10.1001/jama.2021.3224Medications: Side Effects and Considerations
Trial Most Common Side Effects Considerations
Dry mouth 13.5%
MAOIs; Acute Myopia and Secondary Angle
Tingling 13.7%
Phentermine-Topiramate ER Constipation 15.1%
Closure Glaucoma, hyperthyroidism,
Altered taste 7.4% oxalate kidney stones, teratogenic
Oily Spotting Yr 1: 26.6% Yr 2: 4.4%
Flatus with Discharge 23.9% 2.1%
Fecal Urgency 22.1% 2.8%
Pregnancy, chronic malabsorption,
Orlistat Fatty/Oily Stool 20% 5.5%
cholestasis, known hypersensitivity reaction
Oily Evacuation 11.9% 2.3%
Increased Defecation 10.8% 2.6%
Fecal Incontinence 7.7% 1.8%
Nausea 32.5%
Constipation 19.2% MAOIs; Seizure disorders, chronic opioid
Headache 17.6% use, suicidal thinking, anorexia nervosa or
Bupropion-Naltrexone Vomiting 10.7% bulimia, other bupropion-containing
Dizziness 9.9% products
Insomnia 9.2%
Nausea 39.3%
Liraglutide Diarrhea 20.9%
Potential risk of medullary thyroid carcinoma
(Semaglutide similar profile - % of Constipation 19.4%
Vomiting 15.7%
(MTC), pancreatitis, gall bladder disease
side effects are for Liraglutide)
Headache 13.6%
Phentermine/topiramate ER [prescribing information]. Mountain View, CA: Vivus Inc.,2012. https://www.qsymiarems.com/full-prescribing-information.pdf
Orlistat [prescribing information] 2017 CHEPLAPHARM Arzneimittel GmbH. https://xenical.com/pdf/PI_Xenical-brand_FINAL.PDF
Naltrexone HCl/Bupropion HCl [package insert]. Deerfield, IL; Takeda Pharmaceuticals Intl. Inc. 2014. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf
Liraglutide [prescribing information] Novo Nordisk; https://www.novo-pi.com/saxenda.pdf. Semaglutide [prescribing information] Novo Nordisk; https://www.novo-pi.com/wegovy.pdfCase Study - Sarah
▪ Diet: Continue with current membership with Jenny Craig
or consider intermittent fasting?
▪ Exercise: 2 miles 4x/week on average = 120-160 min/week
▪ Depending on intake may need to increase?
▪ Medication:
▪ Orlistat Y/N
▪ Naltrexone/Bupropion Y/N
▪ Phentermine/Topiramate Y/N
▪ Liraglutide Y/N
Surgery???Role of Bariatric Surgery in Obesity and
Associated Metabolic Conditions
▪ Studies show that bariatric surgery causes significant weight loss
and is more effective at improving diabetes in the short term (up
to 2 years) than nonsurgical interventions (diet, exercise, other
behavioral interventions, and medications)
▪ Diabetes improvement starts rapidly after surgery, before
significant weight loss has occurred
▪ The mechanism for postoperative metabolic improvements has
not been fully elucidated and may be, in part, independent of
weight loss
Buchwald H, Estok R, Fahrbach K, et al. Am J Med. 2009 Mar;122(3):248-256. PMID: 19272486.
Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82.
Available at https://effectivehealthcare.ahrq.gov/sites/default/files/related_files/weight-loss-surgery_executive.pdf Accessed April 26, 2021.
Mingrone G, Panunzi S, De Gaetano A, et al. N Engl J Med. 2012 Mar 26;366(17):1577-85. PMID: 22449317.Indications for Surgery
Indications are consensus based and vary between organizations.
All agree to consider surgery on patients with a BMI ≥ 40 or more
than 100 pounds to lose or a BMI ≥ 35 and other significant co-
morbidities.
Other possible indications include:
▪ Patients who have failed other
attempts to maintain a healthy weight
▪ Lower weight patients with
uncontrolled T2DIs the Patient a Surgical Candidate? Beyond meeting NIH/insurance criteria, is the patient... ▪ Motivated to change? ▪ Demonstrating change, already? ▪ Aware of the post-surgical requirements (diet/exercise/vitamins)? ▪ Able to keep post-bariatric visits? ▪ Capable of understanding the process? ▪ Able to afford the required food & vitamins?
Improvement of Comorbidities ▪ Weight loss surgery reliably induces rapid, marked, and durable weight loss among obese patients ▪ Reduces the burden of multiple obesity-associated comorbidities including diabetes, OSA, cardiovascular disease including hypertension, stroke, coronary artery disease and heart failure ▪ May protect against malignancy
Improved Survival with
Weight Loss Surgery
▪ Weight loss surgery patients were prospectively matched to a
control group of 2,037 patients who underwent standard medical
therapy, the risk-adjusted hazard ratio for mortality was 0.71 after a
mean follow up of 10.9 years
▪ A retrospective analysis that matched 2,500 weight loss surgery
patients to 7,462 matched controls in the United States Veterans
Affairs system found that surgical patients had significantly
decreased mortality after one year of follow up, with a hazard ratio
of 0.47 after 5 years
Reges O, Greenland P, Dicker D, Leibowitz M, Hoshen M, Gofer I, et al. Association of bariatric surgery using laparoscopic banding, Roux-en-Y gastric
bypass, or laparoscopic sleeve gastrectomy vs usual care obesity management with all- cause mortality. JAMA 2018;319:279–90.
Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J
Med 2007;357: 741–52.
Arterburn DE, Olsen MK, Smith VA, Livingston EH, Van Scoyoc L, Yancy WS, et al. Association between bariatric surgery and long-term survival. JAMA
2015;313: 62–70.Common Bariatric or
Weight Loss Surgeries (WLS)
Adapted from an illustration by Walter Pories, MD, FACSFollow Up on WLS Patients ▪ At 6 months post expect ▪ ~30-40% Excess Body Weight (EBW) loss ▪ At 12 months post expect ▪ RYGB: 55-70% ▪ Sleeve: 45-60%
Follow Up on WLS Patients ▪ Diet: General composition guidelines ▪ 70 - 80 gm of protein ▪ Protein > vegetables > fruit > carbs ▪ 64 oz of water/equivalents ▪ No carbonation ▪ Avoid: bread/rice/pasta ▪ Avoid sweetened beverages
Obesity in Children ▪ Growing global health issue (especially in US and other developed countries) ▪ No clear-cut recommendations on approach to treatment ▪ Societal barriers (socioeconomics, cultural, environmental) ▪ No FDA approved medications for children ▪ Pediatric Obesity Algorithm originally sponsored by Obesity Medical Association in 2016 to try to address this care gap and uncertainty. Available online at: www.Pediatricobesityalgorithm.org ▪ Identifying and classifying these children as early as possible is important, as is identifying comorbid conditions
Obesity by Race/Sex
▪ Non-Hispanic blacks
(49.6%) had the highest
age-adjusted prevalence of
obesity, followed by
Hispanics (44.8%), non-
Hispanic whites (42.2%)
and non-Hispanic Asians
(17.4%)
1Significantly
different from all other race and Hispanic-origin groups.
2Significantly
different from men for same race and Hispanic-origin group.
NOTES: Estimates were age adjusted by the direct method to the 2000 U.S. Census population using the age groups 20–39, 40–59, and
60 and over.
https://www.cdc.gov/nchs/data/databriefs/db360_tables-508.pdf#page=2 Accessed April 26, 2021.
SOURCE: NCHS, National Health and Nutrition Examination Survey, 2017–2018.Obesity in Pregnancy
▪ Increased risk for:
▪ Miscarriage
▪ Gestational Diabetes
▪ Macrosomia
▪ Preeclampsia
▪ Birth defects - babies born to obese women have an increased risk of
having birth defects, such as heart defects and neural tube defects
▪ Stillbirth - the higher the woman’s BMI, the greater the risk of stillbirth
Source: https://www.acog.org/patient-resources/faqs/pregnancy/obesity-and-pregnancy Accessed April 26, 2021.Summary ▪ Obesity is endemic in the US & the world, and the prevalence is growing ▪ It is easy to diagnose, easy to stigmatize, and difficult to treat ▪ Obesity is a chronic medical condition requiring ongoing care ▪ Associated with multiple serious health risks ▪ Multi-disciplinary approach of diet, exercise, and lifestyle changes remain the backbone of therapy. Close follow-up improves outcomes
Summary
▪ Consider implementing medications earlier as indicated
▪ More serious cases need more serious intervention
▪ Even modest weight loss can significantly affect morbidity and
impact on medical outcomes
Early Intervention!
Don’t wait until BMI of 30 to start the
discussion with your patients.You can also read
