Matching  Patients  to    Weight  Loss  Therapies  

•  Tim  Church  MD  

Key  Takeaways  for  Successful    Weight  Management    

•  Discuss  body  weight  with  patients  using  BMI  and  risk  

factor  values  

•  Engage  patients  in  decision  making  regarding  goals  

and  therapy  

•  Support  and  help  patients  with  lifestyle  modification  

•  Support  with  weight  loss  medications  when  necessary    

•  Engage  patient  lifelong  for  success  and  satisfaction  

Provider Communication Activates

Patients to Lose Weight Patients  advised  to  lose  by  their  

physician  lost  weight  up  to  1  yr  

later,  n>90,000  (Berning  2015)  

PCP’s  underutilize  weight  

management  interventions,  

n>90,000  (Booth  2015)  

Patient  Activation  Improves  

Outcomes,  Reduces  Costs,  

n>32,000  (Greene  2015)  

–  More  activated  patients  =  

Better  health  outcomes  

–  As  patient  activation  increased  =  costs  decreased  

–  If  patient  activation  decreased  =  costs  increased  

–  If  patient  activation  increased  =  costs  decreased  

Patient Activation and Engagement Include Shared Decision Making

Provider  Educates  

•  Medical information •  Patient-friendly •  Uses Aid

Patient  Shares  

•  Concerns •  Values •  Preferences

Decision  Mutual  

•  Care plan •  Follow-up

KEY: SDM Aid and Mobile App

Welcome to PEPtalkTM, a program of PEPeducation.net

PEPtalk clinician downloadable apps provide points-of-care opportunities to engage patients in shared decision-making discussions in your office.

PEPtalk aids are listed by medical problem. Each program can be used on a computer, tablet or smart phone.Patient Aid

Clinician App

PEPtalk is your source for personalized patient education and engagement programs that can activate your patients to improve their health outcomes and reduce costs.

TM

The value of PEPtalk:• Saves time by explaining complicated medical conditions using engaging animated video• Explains therapy options, risks, and side affects in patient friendly terms• Solicits patient values, concerns, and preferences in a private, safe environment• Documents patient input and action• Produces a printable ACTION PLAN for engagement in mutual discussion and decisions

How PEPtalk works:Using two formats, PEPtalk supports Shared Decision-Making efforts between you and your patients. Programs like PEPtalk help patients choose behaviors, adhere to therapy, and be more satisfied with their care.

1. Identify patients with specific therapeutic needs and disease states.2. Send them the PEPtalk SDM Aid link to review and complete.3. Use the PEPtalk Mobile App in your office when reviewing therapeutic options. This SDM tool reinforces learning and engagement.

 How  confident  are  you  that  you  can  support    weight  loss  efforts  in  your  patient    

population?  

•  Very  

•  Somewhat  

•  Not  at  all  

Denise  !  A  39-­‐year-­‐old  African  American  female  

!  Hypertension  for  5  years.    

!  Former  high  school  athlete  

!  Concerned  about  her  weight  gain  after  

having  3  children  (she  has  had  tubal  ligation)  

and  wants  to  get  “back  in  shape.”  

!  Tried  various  diets  without  enduring  results  

!  Concerned  about  her  lack  of  energy.  

Medications:    

•  HCTZ  12.5  mg,  1  tab  daily    

•  Amlodipine  5  mg  daily    

•  Paroxetine  20  mg  daily  

"  Weight:    180  lbs.  

"  Height:    63  in.  

"  BMI:      31.7  kg/m2  

"  WC:      36  in.  

"  BP:      138/88  mmHg  

"  A1C:      5.9%  

"  FBG:      101  mg/dL  

"  TC:      218  mg/dL  

"  TG:      247  mg/dL  

"  LDL-­‐C:    145  mg/dL      

"  HDL-­‐C:    43  mg/dL  

"  Non-­‐HDL-­‐C:    175  mg/dL  

"  TSH:    2.14  miu/mL  

"  Fasting  Insulin:    23  u/mL  

Body  Weight  

Pressure  to  Eat  More  

Pressures  to  Be  Less  Physically  Active  Biology

Behavior Ein Eout

Portion  Sizes,    Soft  drinks/junk  food    Variety    High  Energy  density  food,  Convenience  High  glycemic  index,  Added  Sugar  ,  Great  Taste  Low  Cost,  Easy  food  access,  Ads/marketing    

Sedentary  workplaces/schools/  entertainment  Activity  “unfriendly”  community  design  Drive-­‐through  conveniences  Elevators/escalators  Remote  controls  Labor-­‐saving  devices  Television/computer  

Components of an Effective Obesity Management Program

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

Surgery  or  Medications  

Physical  Activity  

Behavior  Modification  

Diet  

Why  is  5%-­‐10%  Weight  Loss  the  Goal?  

Modest  weight  loss  (5-­‐10%)  can:  

10  1.  Hamman  RF,  et  al.  Diabetes  Care.  2006;29(9):2102-­‐2107.  2.  Look  AHEAD.  www.lookaheadtrial.org/public/bibliography.pdf

DPP1  

-­‐10  

-­‐8  

-­‐6  

-­‐4  

-­‐2  

0  

Weigh

t  los

s  

Years  from  baseline  

Look  AHEAD2  

Diabetes  Support  and  Education  

Intensive  Lifestyle  Intervention    

•  Prevent T2DM1

•  Improve glycemic control in T2DM •  Reduce need for anti-diabetic

agents •  Reduce blood pressure •  Reduce triglycerides •  Increase HDL-C •  Reduce CRP •  Improve symptoms of sleep apnea •  Improve markers of NAFLD

11  

Low  Glycemic  

Low  Fat  

Low  CHO  

Low  Calorie  

Weight and Metabolic Outcomes After 2 Years on a Low CHO vs. Low-Fat Diet A Randomized Trial

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.

12  

Most  Popular  Commercial  Programs    

13  

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  

Provides  food  and  telephone  counseling  

~$280-­‐$370  per  month  

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

Provides  food  and                            in-­‐person  or  telephone  counseling  

~$500-­‐$650  per  month  

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

Internet  Online  Programs  

14  

Exercise  

The Lifestyle Approach

16  

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

Ener

gy E

xpen

ditu

re (M

ETS)

Time (hours)

Sedentary Exercise

Lifestyle Activity

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

Tracking Physical Activity

17  

JawBone Accelerometer Nike FUEL

Fitbug Fitbit BodyMedia

Self-monitoring

Water  Intake  

19  

Look AHEAD Research Group. Arch Intern Med. 2010;170:1566-1575.

How  Much  Weight  Does  the  State-­‐of-­‐the-­‐Art  Lifestyle  Intervention  Produce?  

-­‐0.63   -­‐0.93   -­‐0.92  -­‐1.01  0.00  

-­‐8.5  

-­‐6.35  -­‐5.04  

-­‐4.66  

-­‐9  -­‐8  -­‐7  -­‐6  -­‐5  -­‐4  -­‐3  -­‐2  -­‐1  0  

Year  0   Year  1   Year  2   Year  3   Year  4  

Mean  weight  loss  (%)  from  baseline  by  year  

Diabetes  support  and  education  

 %  W

eigh

t  cha

nge    

P<.0001

Denise  

•  Returns  3  months  later  

having  lost  only  5  lbs.  

•  States  stressful  lifestyle  

leads  to  constant  hunger  

and  stress  eating  

•  Asks  about  weight  loss  

medications  

Current  Medications:    

•  HCTZ  12.5  mg,  1  tab  daily    

•  Amlodipine  5  mg  daily    

•  Paroxetine  20  mg  daily  

Food  Intake  is  Not  Merely  a    Cognitive  Function  

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, oxyntomodulin

Why  Do  We  Need  Drugs    for  Weight  Loss?  

Address  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  loss  

Indications  for  Pharmacotherapy  

•  FDA  prescribing  criteria  

– Adjunct  to  diet  and  increased  physical  ac3vity  for  

adults  with  an  ini3al  BMI  ≥30  kg/m2  or  ≥27  kg/m2  

in  the  presence  of  at  least  one  weight-­‐related  

comorbid  condi3on  

– Chronic  weight  management  

You  decide  that  it  is  reasonable  to  consider  intensifying  treatment  and  add  adjunctive  pharmacotherapy.    Based  on  your  level  of  comfort,  what  is  your  next  step?  

1.  Prescribe  orlistat  

2.  Prescribe  phentermine  

3.  Prescribe  phentermine/topiramate  

4.  Prescribe  lorcaserin  

5.  Prescribe  bupropion/naltrexone  

6.  Prescribe  liraglutide  

7.  Refer  to  an  obesity  medicine  specialist  

8.  Unsure  

Recent  Addi*ons  to  Pharmacotherapy  

ER:  extended  release;  GABA:  gamma-­‐aminobutyric  acid;  NDA:  new  drug  approval;  SR:  sustained  release.    1.  Qsymia  (phentermine  and  topiramate  extended-­‐release)  Prescribing  Informa3on.  Mountain  View,  CA:  VIVUS,  Inc.;  2013.    2.  Belviq  (lorcaserin)  Prescribing  Informa3on.  Woodcliff  Lake,  New  Jersey:  Eisai  Inc.;  2012.  3.  h]p://clinicaltrials.gov/show/  NCT01601704.  Accessed  July  8,  2014.  4.  h]p://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm413896.htm.  Accessed  September  16,  2014.  5.  h]p://clinicaltrials.gov/show/NCT01272219.  Accessed  July  8,  2014.  6.  h]p://novonordisk.com/include/asp/exe_news_a]achment.  asp?sA]achmentGUID=D57A8F09-­‐21EA-­‐4D84-­‐84FE-­‐E2C38B41E25F.  Accessed  September  16,  2014.  

Agents   Ac*on   Approval  

Phentermine/  topiramate  ER1  

•  Sympathomime3c  •  An3convulsant  (GABA  receptor  modula3on,  carbonic  

anhydrase  inhibi3on,  glutamate  antagonism)  •  2012  

Lorcaserin2     •  5-­‐HT2C  serotonin  agonist  •  Li]le  affinity  for  other  serotonergic  receptors   •  2012  

Naltrexone/  bupropion  SR3-­‐4  

•  Dopamine/noradrenaline  reuptake  inhibitor  •  Opioid  receptor  antagonist   •  2014  

Liraglu3de5-­‐6   •  GLP-­‐1  receptor  agonist   •  2014  

Management  Decision  Making  

" Was  my  patient  represented  in  the  pivotal  trials?  

" What  are  the  exclusions/contraindications?  

" What  is  the  effectiveness  of  treatment  (weight  loss)  if  

my  patient  stays  on  the  drug  for  at  least  1  year?  

" What  are  the  side  effects/risks?  

" When  can  I  determine  if  my  patient  is  responsive  to  

treatment?  

Newer  Medications  

Trial   Age  (yrs.)  

BMI  kg/m2  

Co-­‐morbidities   Warnings/Contraindications  

Phentermine-­‐topirimate  ER        Equip        Conquer  

18  –  70  18  –  70    

≥  35  27  -­‐  45  

Metabolic  abnl  Metabolic  abnl  

History  of    nephrolithiasis,  recurrent  major  depression,    suicidal  behavior,  tricyclic    antidepressants    

Lorcaserin      BLOOM      BLOOSOM  

18  –  65  18  –  65      

27  –  45  27  –  45  

Metabolic  abnl  Metabolic  abnl  

Mod/severe  MR,  mild/severe  AR  Depression.  Use  of  SSRI  

Bupropion-­‐  Naltrexone        COR  I      COR  II  

18  –  65  18  –  65  

27  –  45  27  –  45  

Metabolic  abnl  Metabolic  abnl  

History  of  seizures,  serious  psychiatric  illness  Chronic  opioid  use  

Liraglutide      SCALE  Studies   ≥18     ≥27  with  

comorbidity  or  ≥30  

Metabolic  abnl  History  of    pancreatitis  or  FH  of  medullary  thyroid  cancer  or  MEN  II  

Reducing  Body  Weight  by  %  Categories  at  1  Year  with  Adjunctive  Medication  Among  those  who  Complete  

Treatment*  

0.00  

10.00  

20.00  

30.00  

40.00  

50.00  

60.00  

70.00  

80.00  

90.00  

100.00  

Phen/TPM  7.5/46   Phen/TPM  15/92    lorcaserin  10  BID   bupropion/naltrexone  32/360  

liraglutide  3.0  

5%  weight  loss   10%  weight  loss  

*combined  with  lifestyle  modification;  Data  are  from  largest  Phase  III  trial  

%  

Patient  Decision:  Medication  or  No  Medication    (Both  groups  received  Intensive  Behavior  

Modification)  

0  

10  

20  

30  

40  

50  

60  

70  

≥5%   ≥10%   ≥15%  

Participa

nts  (%

)  Placebo   NB32  

Weight  Loss  at  Week  56  

NB32, naltrexone SR 32 mg/d + bupropion SR 360 mg/d Wadden TA, et al. Obesity. 2011;19:110-120.

Newer  Medications:  Side  Effects  and  Considerations  

Trial   Most  Common  Side  Effects  

Considerations  

Phentermine-­‐Topirimate  ER   Dry  mouth                                                            (13.5%)  tingling                                                                        (13.7%)  constipation                                                      (15.1%)  altered  taste                                                      (7.4%)  

MAOIs;  Acute  Myopia  and  Secondary  Angle  Closure  Glaucoma,  hyperthyroidism,  oxalate  kidney  stones,  teratogenic    

Lorcaserin   Headache                                                              (16.8%)  Constipation                                                    (8.3%)    dizziness                                                                    (8.5%)  

MAOIs;  Warning  –  SSRIs,  SNRIs,  triptans  

Bupropion-­‐  Naltrexone     Nausea                                                                        (32.5%)  constipation                                                      (19.2%)    headache                                                                (17.6%)    vomiting                                                                  (10.7%)    dizziness                                                                    (9.9%)    insomnia                                                                    (9.2%)  

MAOIs;  Seizure  disorders,  chronic  opioid  use,  suicidal  thinking,  anorexia  nervosa  or  bulimia,  other  bupropion-­‐containing  products  

Liraglutide   Nausea                                                                        (39.3%)  diarrhea                                                                    (20.9%)  constipation                                                      (19.4%)    vomiting                                                                  (15.7%)  headache                                                                (13.6%)  

Potential  risk  of  medullary  thyroid  carcinoma  (MTC),  pancreatitis,  gall  bladder  disease  

Determining  Responsiveness  

Medication   Responsiveness  Criteria  

Phentermine/topiramate   If  <3%  weight  loss  at  3  months  on  7.5/46  mg  dose,  can  increase  to  15/92  mg  dose.  If  <5%  weight  loss  at  6  months,  discontinue  

Lorcaserin   If  <5%  weight  loss  at  3  months,  discontinue  

Bupropion/naltrexone   If  <5%  weight  loss  at  3  months,  discontinue  

Liraglutide   If  <4%  weight  loss  at  4  months,  discontinue  

Denise  

•  After  7  months  of  monthly  visits  and  encouragement  she  

lost  27  lbs  (15%  of  original  body  weight)  

•  She  is  feeling  great  and  wants  to  lose  another  20  lbs  and,  

most  importantly,  keep  it  off.      

•  Concerned  she  has  not  lost  at  all  this  month  

•  Asks  what  to  do  and  is  this  a  plateau  she  has  heard  about?  

Great  Expectations!!    Patient  Expectations  for  Weight  Loss  

66.5  61.4  

68  74.2  

81.9  

0  

25  

50  

75  

100  

Current  Goal  

Dream  Weight  

Happy  Weight  

Acceptable  Weight  

Disappointed  Weight  

Mea

n  Weigh

t,    kg  

Foster GD, et al. J Consult Clin Psychol. 1997;65:79-85.

≈  33%  loss  

≈  38%  loss  

≈  31%  loss  

≈  25%  loss  

≈  17%  loss  

What  is  a  weight  “plateau”??  A  state  of  energy  balance,    

with  intake  equaling  expenditure,    

where  rate  of  weight  change  is  zero  

What  Causes  Plateau?  

•  There  is  no  “plateau”  

•  Decreased  expenditure  

•  Dietary  adherence  

Plateau:  Weight  loss  first  2  years  

Hall  KD,  et  al.  Lancet  2011;378:826-­‐37.  

What  Causes  Plateau?  

•  There  is  no  “plateau”  

•  Decreased  expenditure  

•  Dietary  adherence  

Energy  Expenditure  Changes  As  Weight  Changes  

Liebel  R,  et  al.  NEJM  1995.  

What  Causes  Plateau?  

•  There  is  no  “plateau”  

•  Decreased  expenditure  

•  Dietary  adherence  

What  To  Do  

•  Don’t  let  the  patient  give  up  

•  Address  expectations  

•  Address  motivations  and  self-­‐assessment  

•  Don’t  let  yourself  (provider)  give  up  

•  Consider  escalating  therapy  

Additive  Effects  of  Treatments  

Wadden  T,  et  al.  Arch  Intern  Med  2001;161:218-­‐227.  

Combination  Pharmacotherapy  

Aronne,  2013.  

Key  Takeaways  for  Successful    Weight  Management    

•  Discuss  body  weight  with  patients  using  BMI  and  risk  

factor  values  

•  Engage  patients  in  decision  making  regarding  goals  

and  therapy  

•  Support  and  help  patients  with  lifestyle  modification  

•  Support  with  weight  loss  medications  when  necessary    

•  Engage  patient  lifelong  for  success  and  satisfaction  

How  confident  are  you  that  you  can  support  weight  loss  efforts  in  your  patient    

population?  

•  Very  

•  Somewhat  

•  Not  at  all  

You  decide  that  it  is  reasonable  to  consider  intensifying  treatment  and  add  adjunctive  pharmacotherapy.    Based  on  your  level  of  comfort,  what  is  your  next  step?  

1.  Prescribe  orlistat  

2.  Prescribe  phentermine  

3.  Prescribe  phentermine/topiramate  

4.  Prescribe  lorcaserin  

5.  Prescribe  bupropion/naltrexone  

6.  Prescribe  liraglutide  

7.  Refer  to  an  obesity  medicine  specialist  

8.  Unsure