OVERVIEW OF OBESITY MANAGEMENT - Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM - INTENSIVE ...
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OVERVIEW OF OBESITY MANAGEMENT
Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM
Past President, 2018
The Obesity Society
Co-Director, Center for Weight Management and Wellness
Division of Endocrinology, Diabetes, and Hypertension
Brigham and Women’s Hospital
Faculty Member
Harvard Medical School
1
Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM
• One of the founding creators of the American Board of Obesity Medicine (ABOM)
• Co-Director for the NIH-funded Boston Nutrition and Obesity Research Center (BNORC)
• President of The Obesity Society in 2017-2018
• Chair of the Endocrine Society Guidelines for Medical Treatment of Obesity, 2015
• Member of the expert panel for updating the 2013 AHA/ACC/TOS Clinical Guidelines for
the Management of Overweight and Obesity in Adults
• Former Nutrition Consultant for the National Aeronautics and Space Administration (NASA)
• Given over 200 invited lectures nationally and internationally
• Published over ten books and over 200 peer-reviewed original research and review articles
on obesity and nutrition
Current research interests are weight change and its effects on adipose tissue metabolism
and inflammation, obesity and cardiovascular disease, resolution of type 2 diabetes and
cardiovascular disease in the bariatric surgery population, disparities in the treatment of
obesity in underserved populations, and novel pharmacotherapeutic agents for the
treatment of obesity.
She is also an expert in sampling subcutaneous adipose tissue and muscle tissue in
humans and has been studying the relationship between adipose tissue inflammation and
obesity for over 15 years
2
Disclosures
• Consultant, Merck • Consultant, Takeda
• Consultant, Nutrisystem • Consultant, Novo Nordisk
• Consultant, Zafgen • Research support, Aspire Bariatrics
• Consultant, Sanofi-Aventis • Research support, GI Dynamics
• Consultant, Orexigen • Research support, Pfizer
• Consultant EnteroMedics • Research support, Gelesis
• Consultant, Scientific Intake • Research support, Orexigen
• Consultant, Set Point health • Research support, Meta Proteomics
• Consultant, Rhythm Pharmaceuticals • Research support, Takeda
• Consultant, Xeno Biosciences • Research support, The Atkins Foundation
• Consultant, Gelesis • Research support MYOS Corporation
• Consultant, Ferring
3
Objectives
• Identify the role of hormonal adaptation in weight
management
• Name the newest anti-obesity FDA-approved
medication and it’s mechanism of action
4
U.S. Prevalence of Obesity, 2017-2018
Adults > 20 years, Obesity = BMI > 30
42.4% 43% 41.9%
TOTAL MEN WOMEN
https://www.cdc.gov/nchs/products/databriefs/db360.htm 5
U.S. Trends in Overweight, Obesity, and Severe Obesity
Adults > 20 years
42.4%
Obesity
BMI > 30
30.7%
Overweight
BMI = 25-29.9
9.2%
Severe Obesity
BMI > 40
https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/obesity-adult.htm 6
Weight Classifications by Body Mass Index (BMI)
Begins at BMI > 25 kg/m2
BMI: 35 >40
Underweight Normal Overweight Obesity I Obesity II Obesity III
Eligibility starts for Eligibility starts for
MEDICATIONS SURGERY
BMI >27 kg/m2 BMI >30 kg/m2
https://www.cdc.gov/healthyweight/assessing/index.html 7
Anti-obesity Drug Treatment Criteria by BMI
Begins at BMI > 27
BMI: 35 >40
Underweight Normal Overweight Obesity I Obesity II Obesity III
BMI >27 kg/m2 BMI >30 kg/m2
with ≥1 comorbidity with no comorbidities
Apovian CM, et al. Obesity (Silver Spring). 2019;27(2):190-204. 8
Bariatric Surgery Criteria by BMI
Begins at BMI > 30
BMI: 35 >40
Underweight Normal Overweight Obesity I Obesity II Obesity III
with Diabetes with ≥1 severe with no
or Metabolic obesity-associated comorbidities
Syndrome comorbidity
with Diabetes or
Metabolic Syndrome
ASMBS Statements/Guidelines | Volume 14, Issue 8, p1071-1087, August 01, 2018
Apovian CM, Aronne LJ, Bessesen D, et al. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62. 9
Why Treat Obesity?
10Designation of Obesity as a Disease
Medical Associations and Societies1 Obesity is a disease:
• American Association of Clinical Endocrinologists leading obesity
• American Academy of Family Physicians groups agree
•
•
American College of Cardiology
American College of Surgeons
June 19
•
•
•
American Medical Association
American Society for Reproductive Medicine
American Urological Association
2013
• The Endocrine Society
• The Obesity Society
• The Society for Cardiovascular Angiography and Interventions
World / National Health Organizations1,2
• World Health Organization
• Food and Drug Administration
• National Institutes of Health
1. ASMBS, TOS, ASBP, AACE Joint Statement. Obesity is a disease: leading obesity groups agree. June 19, 2013.
http://asmbs.org/2013/06/obesity-is-a-disease-leading-obesity-groups-agree/. Accessed September 11, 2013.
2. American Medical Association. AMA Resolution No. 420 (A-13). June 19, 2013.
www.ama-assn.org/assets/meeting/2013a/a13-addendum-refcomm-d.pdf. 11Consequences of Obesity
Memory/cognitive problems
Mental/emotional problems
• Individuals with obesity are at Sleep problems
increased risk for multiple physical Respiratory disease
and psychological morbidities Cardiovascular disease
Hypertension
Type 2 diabetes
• Obesity also has adverse effects
Gastrointestinal Tumors/cancer
on quality of life, disability, and Problems
productivity
• Economic burden of obesity is Fertility problems
Dermatological problems
borne by patients, health care
Osteoarthritis
providers, insurers, and taxpayers
Gout and
rheumatological
problems
Kabiri M, et al. Obesity. 2020;28:429-436. 12All-cause Mortality for Weight Change Patterns
Estimated 12.4% OF EARLY DEATHS
may be attributable to having weight in
excess of the normal BMI range at any
point between early and mid-adulthood
(95% CI, 8.1%-16.5%)
For all participants, maintaining an obese
BMI from early adulthood to midlife
increased the risk of all-cause mortality
vs. stable normal weight, with an HR of 2.17
(95% CI, 1.85-2.53)
• Weight gain from a normal to overweight BMI was
not associated with risk, normal-obese (HR, 1.32;
95% CI, 1.15-1.52)
• Overweight to obese (HR, 1.47; 95% CI, 1.28-1.69)
weight changes were associated with elevated
mortality risks
JAMA Network Open. 2020;3(8):e2013448. 13Why is it so Hard to
Lose Weight?
14Neuronal and hormonal pathways influencing food intake and satiety in the brain Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24. 15
Complex Peripheral Signals are Integrated into CNS
Systems to Regulate Body Weight
PfC
Brain systems (homeostatic and Striatum
reward) receive and integrate NAc
peripheral and other CNS Hypothalamus
VTA
signals (eg, dopamine, Peripheral signals
Hindbrain
serotonin)1,2 are relayed to brain
Leptin, insulin, and ghrelin are integrated systems via blood
directly into hypothalamus and vagus nerve 1,2
Peripheral signals
are released
CNS, central nervous system
by pancreas,
PfC, prefrontal cortex
NAc, nucleus accumbens
gastrointestinal
VTA, ventral tegmental area
PP, pancreatic polypeptide system, and
CCK, cholecystokinin;
GLP-1, glucagon-like peptide 1 adipose tissue1,2
OXM, oxyntomodulin
PYY, peptide YY.
Primarily based on data from animal studies. Appetite Stimulating
Appetite Suppressing
1. Yu JH et al. Diabetes Metab J. 2012;36(6):391-398.
2. Mendieta-Zerón H et al. Gen Comp Endocrinol. 2008;155:481-495. Adapted with permission from Mendieta-Zerón H et al.2 16Obesity Associated with Hypothalamic
Injury in Rodents and Humans
• Rodent models of obesity, induced by consuming high-fat diet (HFD), are
characterized by inflammation both in peripheral tissues and hypothalamic areas
critical for energy homeostasis
• Unlike inflammation in peripheral tissues, which develops as a consequence of
obesity, hypothalamic inflammatory signaling was evident in both rats and mice
within 1 to 3 days of HFD onset, prior to substantial weight gain
• Both reactive gliosis and markers suggestive of neuron injury were evident in the
hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding
• Evidence of increased gliosis in the mediobasal hypothalamus of obese humans,
as assessed by MRI
Findings suggest obesity is associated with neuronal injury
in a brain area crucial for body weight control
in both humans and rodent models
Thaler PT, et al. J Clin Invest. 2012 Jan 3;122(1):153-62. doi: 10.1172/JCI59660. Epub 2011. 17Translation of Defense of the
Body Weight Set Point:
• 2009, 50 obese men and women
• Men 233 lbs/average
Women 200 lbs/average
• Extreme low-calorie diet
• Optifast shakes + 2 cups of low-starch
vegetables
• Total 500-550 kcal/d for eight weeks
• At 10 weeks: 30-lb ave. weight loss
At year one: 11-lb ave. weight regain
• Reported feeling more hungry and preoccupied Body continues to fight
against weight loss long
with food than before the weight loss after dieting has stopped
Sumithran P et al. N Engl J Med. 2011;365:1597-1604. 1814% Weight Loss Produced Changes in
Eight Hormones That Encourage Weight Regain
Mean fasting and postprandial levels of some peripheral signals at baseline and 62 weeks
Reduced Increased 10-week, lifestyle-based
weight loss intervention in
Leptin - 65% Ghrelin healthy overweight and obese
Peptide YY Pancreatic polypeptide adults (n=34)
Cholecystokinin Gastric inhibitory
Insulin polypeptide Led to sustained elevations
Amylin in appetite stimulating
hormone(s) and decreases
Measures of appetite in appetite suppressing
hormones
Sumithran P et al. N Engl J Med. 2011;365:1597-1604. 19Long-Term Persistence of Hormonal
Adaptations to Weight Loss
Changes in Weight
11-lb
from Baseline to GAIN
Week 62
30-lb
LOSS
10 week
weight-loss
program
Sumithran P et al. N Engl J Med. 2011;365:1597-1604. 20Obesity Guidelines
212013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and The Obesity Society July 1, 2014 J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023. 22
2013 Guidelines: Recommendations 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults • Use BMI to identify risk; advise patients of their risk • Use waist circumference to identify risk; advise patients of their risk • 3%-5% sustained weight loss reduces risk factors and risk of diabetes • Prescribe set number of calories per day • There is no ideal diet • Advise obese adults who meet criteria that surgery may be an option J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023. 23
Obesity Guidelines: Recommendation 3
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
Prescribe a diet to achieve reduced calorie intake for obese or
overweight individuals who would benefit from weight loss, as part
of a comprehensive lifestyle intervention. Any one of the following
methods can be used to reduce food and calorie intake:
• 1,200–1,500 kcal/d for women
Prescribe 2021
• 1,500–1,800 kcal/d for men
(adjust for individual’s body weight); SET NUMBER OF
• 500 or 750-kcal/d energy deficit CALORIES/DAY
• Prescribe one of the evidence- Flexitarian
based diets that restricts certain Diet
Choose an
food types (such as high-carb flexible and vegetarian
foods, low-fiber foods, or high-fat
evidence-based diet – Best for weight loss
foods) in order to create an energy there is NO IDEAL DIET
deficit by reduced food intake
J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults 24Where
Obesity Appetite Suppressing
DRUGS
Treatments Hypothalamus
Work
LAGB surgery
Stomach
DRUG:
Lipase Inhibitors (Orlistat)
Intestines
Gastric Bypass, BPD
Gastric Sleeve surgeries
Intestines
Source of photo: Mendieta-Zerón H1, López M, Diéguez
C.Gen Comp Endocrinol. 2008 Feb 1;155(3):481-95. 25Problem: Treatment Gap in Mid-BMI Range
How to fill this gap?
Sleeve gastrectomy
Gastric
DIET AND Lap Band Bypass BPD
LIFESTYLE
& DRUGS BARIATRIC SURGERY
NOT EFFECTIVE
enough Treatment
for many people TOO RISKY
Gap for many people
0% 5% 10% 15% 20% 25% 30% 35%
Weight Loss
After Aronne L. FDA EMDAC 2010. 26Anti-obesity
Medications
27Rationale for Obesity Pharmacotherapy
• Obesity causes more than 200 other medical disorders
that affect entire organ systems
• Accounts for ~4 million deaths worldwide and a high
cardiovascular disease burden
• Prevalence is rapidly increasing
Highlights the immediate need for
early recognition and treatment
in the context of the
existing available therapeutic armature
Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24. 28Medical Treatment for Obesity vs T2DM
50%
Adults in the U.S.
U.S. Adult Population (%)
45%
Indicated Treated
40%
35%
30%
25%
20%
15%
10%
5%
0%
Obesity Type 2 Diabetes
CDC, National Center for Health Statistics, Division of Health Interview Statistics, data from the National Health Interview Survey.
Cowie CC, et al. Diabetes Care. 2009 Feb;32(2):287-94.
Samaranayake NR, et al. Ann Epidemiol. 2012 May;22(5):349-53. 29Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline January 15, 2015 Apovian CM, Aronne LJ, Bessesen D, et al. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62. 30
FDA Approval Criteria: Anti-obesity Drug
• Standard guidelines were issued in the mid-1990s
• A new drug must induce statistically significant placebo- adjusted
weight loss of:
• >5% at 1 year or
• >35% of patients should achieve >5% weight loss
(which must be at least twice that induced by placebo)
• In addition, the medication is required to show evidence of
improvement in metabolic biomarkers, including blood pressure,
lipid levels and glycemic control
www.fda.gov/downloads/Drugs/Guidances/ucm071612.pdf 31FDA Approves New Drug Treatment for Chronic
Weight Management, First Since 2014
• Approved June 04, 2021
• Indicated for chronic weight management in patients with
BMI > 27 kg/m2 with at least one weight-related ailment or
BMI > 30 kg/m2
• Works by mimicking GLP-1, targeting areas of the brain
that regulate appetite and food intake
• Dosing must be increased gradually over 16 to 20 weeks to 2.4 mg
once weekly to reduce gastrointestinal side effects
• N = >2,600 patients up to 68 weeks in four studies with
>1,500 patients receiving placebo
https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 32FDA Approves New Drug Treatment for Chronic
Weight Management, First Since 2014
Trial of pts without diabetes:
• 46 years average age Adverse Effects
• 74% female nausea, diarrhea,
• 231 lbs (105 kg) average body weight vomiting, constipation,
abdominal pain,
• 38 kg/m2 average BMI headache, fatigue,
• Lost average of 12.4% initial body weight vs. placebo dyspepsia, dizziness,
abdominal distension,
Trial of pts with type 2 diabetes: eructation,
hypoglycemia) in
• 55 years
patients with type 2
• 51% were female diabetes, flatulence,
• 220 lbs (100 kg) gastroenteritis,
gastroesophageal
• 36 kg/m2 average BMI reflux disease
• Lost 6.2% of initial body weight vs. placebo
https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 33Effects of Once-Weekly
Semaglutide vs. Placebo,
on Body Weight
• Significant reduction in body
weight from baseline
• –14.9% semaglutide group vs.
–2.4% placebo group
• Greater mean weight loss
• –15.3 kg semaglutide group vs.
–2.6 kg placebo group
• Greater weight loss of at least 5%
• 86.4% in semaglutide group vs.
placebo (31.5%)
Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989. 34Efficacy of Current Anti-obesity Drugs
Semaglutide (Wegovy)
(Wilding et al. 2021) 2.4 mg once weekly injection for 68 wks
Phentermine/topiramate ER
(Gadde et al. 2011) 7.5/46 mg for 1 year
Phentermine
(Aronne et al. 2013) 15 mg daily for 28 wks
Naltrexone SR/bupropion SR
(Greenway et al. 2010) Maximum dose for 56 wks
Liraglutide (Saxenda)
package insert 2014 3.0 mg for 56 wks
Orlistat 120 mg thrice
(Aronne et al. 2013) daily for 1 year
0 1 2 3 4 5 6 7 8 9 10 11 12 13
% Estimated weight loss (drug minus placebo)
Indicated to be used as adjuncts to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a BMI ≥30 kg/m2 or
those with a BMI ≥27 kg/m2 who have at least one weight-related comorbid condition such as diabetes mellitus, hypertension, hyperlipidemia or sleep apnea
Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.
Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989. 35Current Obesity Pharmacotherapy for Long-term Use
Mesolimbic Reward System
Naltrexone/bupropion
µ-opioid antagonist +
DA/NE reuptake inhibitor Hypothalamus
Mesolimbic
Reward System
Hypothalamus
Phentermine/topiramate Dorsal Vagal
Sympathomimetic amine + antiepileptic Hypothalamus Complex
Dorsal Vagal
complex Orlistat
Liraglutide and Lipase inhibitor
NEW Semaglutide Hypothalamus
GLP-1 receptor agonist Intestines
5-HT2c=serotonin; DA=dopamine; GLP-1=glucagon-like peptide-1; MOA=mechanism of action; NE=norepinephrine.
1. Yanovski SZ et al. JAMA. 2014;311:74-86. 2. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342-362.
3. Kim GW et al. Clin Pharmacol Ther. 2014;95:53-66. 4. Dietrich MO et al. Nat Rev Drug Discov. 2012;11:675-691. 37Pharmacotherapy Increases Magnitude
and Likelihood of Weight Loss
PBO ORL LOR PHEN/TPM ER BN LIRA
80 75 73
72 70
67 67
Patients with ≥5% WL
64
60 54
47 48 50
45 45 45 44
41
40
30 27 28
25 22
20 21 19
20 16 17 16 17
0
BLOOM
COR-BMOD
BLOOM-DM
SEQUEL*
XENDOS
CONQUER
COR-D
BLOSSOM
COR-II
SCALE Maintain
EQUIP
COR I
SCALE Obesity
Astrup et al (2012)
Pucci A, et al. Can J Cardiol. 2015;31(2):142-152. Astrup A, et al. Int J Obes (Lond). 2012;36(6):843-854. 38NEW –
borrowed from
Long-term Ongoing Therapy Needed for Ivania Rizo
Obesity Treatment
AOM
stopped
Schalles, et al. Visc Med. 2016, figure adapted by Ania Jastreboff, MD, PhD. 39Medications: Assessing Efficacy and Safety
Effective Ineffective
Loss of ≥5% body weight Loss ofAdding
Pharmacotherapy
to Bariatric Surgery
41Surgery: Better Weight Loss than Lifestyle and Medical Mngt
The Diabetes Surgery Study Randomized Clinical Trial
7.3%
Difference, 17%
95% CI, 13-20%
23.8%
Ikramuddin S, et al. Lancet Diabetes Endocrinol. 2015 Jun;3(6):413-22. 42Surgery: Best Long-term Weight Loss Results
% Weight Change: -18% mean change in body weight over 20 years
Nonadjustable or Adjustable
Vertical Banded Gastroplasty
Gastric Bypass
Sjöström L. J Intern Med. 2013 Mar;273(3):219-34. 43Resolution or Improvement in Comorbidities
Varies by Type of Surgery
90
Band Sleeve Bypass
% Resolution or Improvement
80
82 78
70
60 65 68
62 60
50 58
55
50
40
40
30 35 35
20
10
0
Diabetes HTN Sleep Apnea GERD
N = >28K x 3 years
Hutter et al. Ann Surg. 2011 Sep;254(3):410-20; discussion 420-2. 44Bariatric Surgery Procedures
Sleeve Gastrectomy Gastric Bypass Gastric Band
(LAP-BAND)
• Average weight loss: • Average weight loss:
• Not commonly performed as
– 25% of total weight – 30% of total weight weight loss results have not
• Surgery takes about 60 minutes • Surgery takes about 90-120 minutes been optimal in the long-term
• 1 day in hospital • 1-2 days in hospital • Our team will consider this
• Limits ingestion of food and • Limits ingestion of food and changes operation on a case-by-case
changes hunger signals hunger signals basis
• Non-reversible • Reversible in extreme cases
45The Problem
Patients who undergo bariatric
surgery often have:
– Inadequate weight loss
(Phentermine and Topiramate Reduce the
Occurrence of Rapid Weight Regain after RYGB
Phentermine and
topiramate, used
individually or in
combination, can
significantly reduce
WR after RYGB
N= 760
350 (46.1%) used AOMs
• 119 (34.0%) phentermine
• 74 (21.1%) topiramate
• 154 (44.0 %) combination
of phentermine and
topiramate
Istfan NW, Apovian CM, et al. Obesity (Silver Spring). 2020 Jun;28(6):1023-1030. 47Utility of Weight Loss Medications After Weight Loss Surgery
Design N=319 patients
• Retrospective study 2000-2014 • RYGB = 258
• Sleeve gastrectomy = 61
Setting
• 2 Academic Institutional Practices
Patients and Other Participants
• Patients who had undergone Roux-en-Y gastric bypass (RYGB) or a
vertical sleeve gastrectomy (VSG) who were subsequently placed on
weight loss pharmacotherapy post-operatively
• Of the 5110 charts reviewed, 319 met inclusion criteria
Interventions
• Weight loss pharmacotherapy: 15 FDA and non-FDA approved meds
Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500. 48Utility of Weight Loss Medications After Weight Loss Surgery
Results
• 54%, n=172 of all study patients lost ≥ 5% of their total body weight with
post-surgery weight loss pharmacotherapy
• High responders:
• 30.3% (n=96) lost ≥ 10% of their total body weight
• 15% (n=49) lost ≥15% of their total body weight
• Topiramate – the only medication demonstrating statistically significant
weight loss with patients being twice as likely to lose at least 10% of their
weight (OR=1.9, p=0.018)
• RYGB patients were significantly more likely to lose ≥ 5% of their total body
weight with the aid of weight loss medications vs. VSG patients (regardless
of postop BMI)
• Total body weight loss from surgery plus weight loss pharmacotherapy
• 26.8% (SD=10.5) [4.3-60.2%] patients starting meds after weight regain
• 32.3% (SD=11.4) [8.3-56.3%] patients starting meds at their weight plateau after
bariatric surgery (p=0.486)
Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500. 49Demonstration of the utility of weight loss mediation after bariatric surgery in a RYGB patient Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500. 50
Keys for Long-term
Success
51Long-term Weight Loss Long-term treatment with regular support can be effective1-5 Weight must be managed on an ongoing basis5-9 1. Elmer PJ, et al. Annals of Internal Medicine, 144:485–495, 2006. 2. Wadden TA. Annals of Internal Medicine, 119(7):688–693, October 1993. 3. Tate DF. JAMA, 289(14):1833–1836, April 9 2003. 4. Tate DF, Wing RR, Winett RA. JAMA 285(9):1172–1177, March 7 2001. 5. Ness-Abramof R, Nabriski D, Apovian CM. The Israel Medical Association Journal, 6:760–765, December 2004. 6. Wadden TA, Brownell KD, Foster GD. Journal of Consulting and Clinical Psychology, 70(3):510–525, 2002. 7. Wadden TA, Foster GD, Letizia KA. Journal of Consulting and Clinical Psychology, 62(1):165–171, 1994. 8. Wadden TA, et al. Archives of Internal Medicine, 161:218–227, 2001. 9. Wadden TA, et al. NEJM, 353(20):2111–2122, November 2005. 52
Frequent Patient Follow-up is Key
All patients prescribed weight loss medications:
JAN FEB MAR APR MAY JUNE JULY AUG SEPT OCT NOV DEC
At least monthly Then at least
for first 3 months every 3 months
Centers for Medicare & Medicaid Services coverage:
Month 1 Four visits (1 per week) 15 visits per year
Months 2-6 One visit per month
if 3 kg (6.6 lbs) lost, then:
Month 7-12 One visit per month
www.cms.gov Decision Memo for Intensive Behavioral Therapy for Obesity (CAG-00423N). 53Bariatric Surgical Patients Require Lifelong Follow-up Visits
Encourage All patients are encouraged to drink water long-term
Consumption of lean protein sources is encouraged
Vitamin and mineral supplementation should be reinforced at every visit
to avoid micronutrient deficiencies
Routine exercise should be encouraged
• Walking is an appropriate way to start exercising
• Patients with degenerative joint disease may benefit from aquatic exercise to reduce joint pain
Discourage Caffeinated beverages should be avoided because of the diuretic effect
Processed snack foods and sweetened beverages are discouraged because
they increase calorie intake unnecessarily
Carbonation and straws because of the risk of gastric bloating
https://www.uptodate.com/contents/bariatric-surgery-postoperative-and-long-term-management-of-the-uncomplicated-patient 54Successful Long-term Weight Loss
National Weight Control Registry: Lifestyle Changes
• 10,000 registrants Ten Year NWCR Data
• Maintaining 66 lb loss for 5 years • N=2886 who lost 31 kg
maintained for 5 years
• Eat 1800 kcal/day with 27% fat
• Regain at end of 10 years but
• Perform 2700 kcal/week exercise still lost 30% total body
weight then gained to 22.6%
• 40% weigh themselves daily total weight loss
• 20% weekly • 10 year loss = 23 kg (50.6 lbs)
• Reduced TV watching • Weight regain levels out from
• Limit diet variety 5 years to 10
• 78% eat breakfast • 85% of registrants lost 20%
• Eat fast food once per week • 40% of registrants lost 30%
• Use more artificially sweetened • If exercise decreased by 500
kcal per week they regain 9 kg
beverages than others of normal weight
• If exercise is maintained they
• They are VIGILANT regain only 4.5% or 4.5 kg
National Weight Control Registry http://www.nwcr.ws/ Thomas JG, et al. Am J Prev Med. 2014 Jan;46(1):17-23. 55Maintaining Weight Loss http://www.nwcr.ws/
National Weight Control Registry
Better long-term outcomes with:
N=2886
• Larger initial weight losses
• Longer duration of maintenance
Greater weight REGAIN associated with:
• Decreases in leisure-time physical
activity
• Decreases in dietary restraint
Mean weight loss: • Decreases in self-weighing frequency
Baseline: 31.3 kg (95% CI=30.8, 31.9) • Increases in percent of intake from fat
5 Years: 23.8 kg (95% CI=23.2, 24.4) and disinhibition
10 Years: 23.1±0.4 kg (95% CI=22.3, 23.9)
>87% were estimated to be maintaining >10% weight loss at Years 5 and 10
Thomas JG, Bond DS, Phelan S, Hill JO, Wing RR. Am J Prev Med. 2014 Jan;46(1):17-23. 56Percentage Weight Loss by Minutes of Physical
Activity (calories per week)
Total n=170
= >1000 kcal/wk)
= >2000 kcal/wk)
maintained 3x
the weight loss
vs. those at 150 min/wk
Wadden TA, et al. Circulation. 2012;125:1157-70. 57Adherence - Not Diet - Predicts Success
• Consistent finding in four
2012 meta-analyses, each
summarizing 13 to 24 trials:
adherence was most strongly
associated with weight loss1-4
• Meta-analysis 2014: 48 trials,
n = 7,286; conclusion:
any diet a patient will adhere
to lose weight is best5
1. Ajala O, English P, Pinkney J. Am J Clin Nutr. 2013 Mar;97(3):505-16.
2. Wycherley TP, et al. Am J Clin Nutr. 2012 Dec;96(6):1281-98.
3. Hu T, et al. Am J Epidemiol. 2012 Oct 1;176 Suppl 7:S44-54.
4. Bueno NB, et al. Br J Nutr. 2013 Oct;110(7):1178-87.
5. Johnston BC, et al. JAMA. 2014;312(9):923-933. 58Barriers to Success
59Drugs That Tend to Promote Weight Gain, Weight
Loss, or Are Weight Neutral
Weight GAIN Weight LOSS or Weight NEUTRAL
Diabetes Treatments Diabetes Treatments
• Insulin • Exenatide, liraglutide, pramlintide
• Sulfonylureas • Sitagliptin
• Thiazolidinediones • Metformin
• Acarbose, miglitol
• Canagliflozin
Psychiatric/Neurologic Psychiatric/Neurologic
• Antipsychotics • Ziprasidone, aripiprazole
• Antidepressants • Bupropion
• Antiepileptics • Topiramate, zonisamide,
• Lithium lamotrigine
Adapted from
Aronne LJ, Segal KR. J Clin Psychiatry. 2003;64(Suppl 8):22-29. Leslie WS, et al. QJM. 2007;100(7):395-404. Messerli FH, et al. Am J Med. 2007;120(7):610-615.60Ultra-processed Foods
May Facilitate Overeating
• Rise in obesity and type 2 diabetes prevalence How Often Food was
Selected as Problematic
occurred in parallel with increasingly industrialized Top 10 of 35
food system
• Large scale production of high yield, inexpensive, Food Ratings Based on
agricultural “inputs” (corn, soy, wheat), refined and 7-point Likert Scale
Not Problematic to Extremely
processed Top 10 of 35
• Highly processed foods, with added amounts of fat
and/or refined carbohydrates (e.g., sugar, white
flour), were most likely to be associated with
behavioral indicators of addictive-like eating
• Additionally, foods with high GL were especially
related to addictive-like eating problems for
individuals endorsing elevated symptoms of “food
addiction”
Poti JM, et al. Curr Obes Rep. 2017 Dec;6(4):420-431.
Schulte EM, et al. PLoS One. 2015 Feb 18;10(2):e0117959. 61Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain
• 20 inpatient adults received ultra-
processed and unprocessed diets
for 14 days each
• Diets were matched for presented
calories, sugar, fat, fiber, and
macronutrients
• Ad libitum intake was ~500
kcal/day more on ultra-processed
vs unprocessed diet
• Body weight changes were highly
correlated with diet differences in
energy intake
Hall KD, et al. Cell Metab. 2019 Jul 2;30(1):67-77.e3. 62Treatment Gap in Mid-BMI Range
New drugs and devices can reduce weight and weight-related comorbidities
Drug options:
Liraglutide
NEW Semaglutide
Combination
Pharmacotherapy
Prior to 2012: Phen/top
Orlistat Nalt/bup Sleeve gastrectomy
Phentermine Gastric
DIET AND
Less Invasive Lap Band Bypass BPD
Procedures
LIFESTYLE Vagal block therapy
& DRUGS Endoscopic sleeve BARIATRIC SURGERY
NOT EFFECTIVE
enough Treatment
for many people TOO RISKY
Gap for many people
0% 5% 10% 15% 20% 25% 30% 35%
Weight Loss
The gap is being filled
After Aronne L. FDA EMDAC 2010. 63Summary
• Overweight and obesity are measured by Body Mass Index (BMI)
• 42.4% of U.S. Adults have obesity
• 30.7% of U.S. Adults are overweight
• Lifestyle interventions can be effective with long-term follow-up
• Bariatric surgery is the most effective form of long-term weight loss
• Weight regain occurs in 17-30% of RYGB patients at two years post-op
• Anti-obesity medications are effective at increasing post-op weight loss
and preventing weight regain
• New GLP-1 agonist, semaglutide, shows promise to help fill BMI-mid-
range treatment gap
64References
• Cowie CC, et al. Diabetes Care. 2009 Feb;32(2):287-94.
• Samaranayake NR, et al. Ann Epidemiol. 2012 May;22(5):349-53.
• https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/obesity-adult.htm
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• ASMBS Statements/Guidelines | Volume 14, Issue 8, p1071-1087, August 01, 2018
• ASMBS, TOS, ASBP, AACE Joint Statement. Obesity is a disease: leading obesity groups agree. June 19, 2013. http://asmbs.org/2013/06/obesity-
is-a-disease-leading-obesity-groups-agree/. Accessed September 11, 2013.
• American Medical Association. AMA Resolution No. 420 (A-13). June 19, 2013.
www.ama-assn.org/assets/meeting/2013a/a13-addendum-refcomm-d.pdf.
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• Yu JH et al. Diabetes Metab J. 2012;36(6):391-398.
• Mendieta-Zerón H et al. Gen Comp Endocrinol. 2008;155:481-495.
• Thaler PT, et al. J Clin Invest. 2012 Jan 3;122(1):153-62. doi: 10.1172/JCI59660. Epub 2011.
• Sumithran P et al. N Engl J Med. 2011;365:1597-1604.
• J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023.
• Mendieta-Zerón H1, López M, Diéguez C.Gen Comp Endocrinol. 2008 Feb 1;155(3):481-95.
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65References • www.fda.gov/downloads/Drugs/Guidances/ucm071612.pdf • https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014. • Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989. • Yanovski SZ et al. JAMA. 2014;311:74-86. • Kim GW et al. Clin Pharmacol Ther. 2014;95:53-66. • Dietrich MO et al. Nat Rev Drug Discov. 2012;11:675-691. • Pucci A, et al. Can J Cardiol. 2015;31(2):142-152. • Astrup A, et al. Int J Obes (Lond). 2012;36(6):843-854. • Schalles, et al. Visc Med. 2016, figure adapted by Ania Jastreboff, MD, PhD. • Ikramuddin S, et al. Lancet Diabetes Endocrinol. 2015 Jun;3(6):413-22. • Sjöström L. J Intern Med. 2013 Mar;273(3):219-34. • Hutter et al. Ann Surg. 2011 Sep;254(3):410-20; discussion 420-2. • Istfan NW, Apovian CM, et al. Obesity (Silver Spring). 2020 Jun;28(6):1023-1030. • Stanford FC, Aronne LJ, ET AL. Surg Obes Relat Dis. 2017 Mar;13(3):491-500. • Elmer PJ, et al. Annals of Internal Medicine, 144:485–495, 2006. • Wadden TA. Annals of Internal Medicine, 119(7):688–693, October 1993. • Tate DF. JAMA, 289(14):1833–1836, April 9 2003. • Tate DF, Wing RR, Winett RA. JAMA 285(9):1172–1177, March 7 2001. • Ness-Abramof R, Nabriski D, Apovian CM. The Israel Medical Association Journal, 6:760–765, December 2004. • Wadden TA, Brownell KD, Foster GD. Journal of Consulting and Clinical Psychology, 70(3):510–525, 2002. • Wadden TA, Foster GD, Letizia KA. Journal of Consulting and Clinical Psychology, 62(1):165–171, 1994. • Wadden TA, et al. Archives of Internal Medicine, 161:218–227, 2001. • Wadden TA, et al. NEJM, 353(20):2111–2122, November 2005. 66
References
• www.cms.gov Decision Memo for Intensive Behavioral Therapy for Obesity (CAG-00423N).
• https://www.uptodate.com/contents/bariatric-surgery-postoperative-and-long-term-management-of-the-uncomplicated-patient
• National Weight Control Registry http://www.nwcr.ws/
• Wadden TA, et al. Circulation. 2012;125:1157-70.
• Ajala O, English P, Pinkney J. Am J Clin Nutr. 2013 Mar;97(3):505-16.
• Wycherley TP, et al. Am J Clin Nutr. 2012 Dec;96(6):1281-98.
• Hu T, et al. Am J Epidemiol. 2012 Oct 1;176 Suppl 7:S44-54.
• Bueno NB, et al. Br J Nutr. 2013 Oct;110(7):1178-87.
• Johnston BC, et al. JAMA. 2014;312(9):923-933.
• Aronne LJ, Segal KR. J Clin Psychiatry. 2003;64(Suppl 8):22-29.
• Leslie WS, et al. QJM. 2007;100(7):395-404.
• Messerli FH, et al. Am J Med. 2007;120(7):610-615.
• Hall KD, et al. Cell Metab. 2019 Jul 2;30(1):67-77.e3.
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