Transcript www.wmshp.net

WEIGHT MANAGEMENT:
A TEAM APPROACH
Crystal Whitman, PharmD, BCACP
Aleda E. Lutz VA Medical Center
Saginaw, MI
OBJECTIVES
1. Evaluate the current guidelines for the
management of overweight and obesity in adults.
2. Identify the components of a high-intensity,
comprehensive-lifestyle intervention program.
3. Review treatment options that may aid patients
in their weight loss goals.
CASE 1

MK is a 32 y.o. hispanic female with body mass
index (BMI) of 32. She has a diagnosis of
hypertension (HTN) and hypothyroidism. She
discusses her and her spouse’s desire to become
pregnant within the next year and her
frustrations with her current weight. She reports
‘trying really hard at home’ without success.
What is your recommendation?
A. phenteramine/topiramate (Qsymia)
B. diethylpropion
C. a comprehensive lifestyle intervention
program
D. bariatric surgery
WHAT DO WE KNOW?
HTN
Cancer:
endometrial,
breast,
prostate, and
colon
Sleep apnea &
respiratory
problems
Dyslipidemia
Type 2
diabetes
(T2DM)
Obesity and
overweight
increase the risk
of morbidity from
Coronary
heart disease
(CHD)
Osteoarthritis
Gallbladder
disease
Stroke
Obesity Trends* Among U.S. Adults
BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
No Data
<10%
10%–14%
15%–19%
20%–24%
www.cdc.gov/obesity/downloads/obesity_trends_2010.ppt
BRFSS: Behavioral Risk Factor Source Surveillance System
25%–29%
≥30%
STATISTICS

More than one-third of
U.S. adults (35.7%) are obese


31.0%
33.3%
Normal
Overweight
Obese
The estimated annual medical cost of obesity in
the U.S. was $147 billion in 2008 U.S. dollars


Overweight (BMI>25)= 69%
35.7%
$99.2 billion in 1995
The medical costs for people who are obese were
$1,429 higher than those of normal weight
http://www.cdc.gov/obesity/data/adult.html
NIH, NHLBI. Clinical Guidelines on the identification, evaluation, and treatment of overweight
and obesity in Adults. The evidence report. NIH Publication No. 98-4083, 1998.
WHO RESPONDED?
 National
Heart, Lung, Blood Institute
(NHLBI) in cooperation with the National
Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK)

Identification, Evaluation, and Treatment of
Overweight and Obesity In Adults (1998)
Examined the evidence of benefits
 Assessment/classification: BMI, waist circumference
 Goals of weight loss and management (1-2 lbs/week)
 Strategies for weight loss and management





Pharmacotherapy
Bariatric Surgery
Diet therapy (500 to 1000 kcal/d deficit)
Physical Activity (30 min moderate intensity most days)
TIME FOR AN UPDATE

2013 American Heart Association
(AHA)/American College of Cardiology (ACC)/The
Obese Society (TOS) Guideline for the
Management of Overweight and Obesity in
Adults
2008 NHLBI initiated
 June 2013 began collaboration with ACC/AHA
 Other ACC/AHA 2013 guidelines

Assessment of cardiovascular (CV) risk
 Lifestyle modifications to reduce CV risk
 Blood cholesterol

2013 OVERWEIGHT/OBESITY
GUIDELINES
 Differ


from other ACC/AHA guidelines
More limited in scope
Focus on select critical questions (CQ) based
on the highest quality evidence available
 Recommendations



derived
Randomized trials
Meta-analyses
Observational studies evaluated for quality
 Evidence
not considered beyond 2011
2013 OVERWEIGHT/OBESITY
GUIDELINES
 Panel
began with 23 possible CQ
 Excluded CQ

Examples: genetics, binge, pharmacotherapy, cost
effectiveness
 Panel’s

Develop evidence statements (ES) and
recommendations for 5 CQs to assist clinicians
in primary care
 Our


ultimate goal
goal today
Discuss summary of recommendations
Discuss 4 CQ and selected ES
2013 OVERWEIGHT/OBESITY
GUIDELINES: CQ
CQ1: address the expected health benefits of
weight loss
CQ2: (i) address the health risk of
overweight and obesity (ii) determine if
waist circumference/BMI cutpoints
appropriate across all subgroups
CQ3: which dietary intervention strategies
are effective for weight loss efforts
CQ4: determine the efficacy and
effectiveness of a comprehensive lifestyle
approach on weight loss and maintenance
CRITICAL QUESTION 1 (CQ1)

Among overweight and obese (O/O) adults, does
achievement of reduction in body weight with
lifestyle and pharmacological interventions affect
cardiovascular disease (CVD) risk factors, CVD
events, morbidity and mortality?
Weight loss and risk of diabetes
 Weight loss and impact on cholesterol/lipid profile
 Weight loss and hypertension risk

CQ1 (DM)
Weight loss and risk of diabetes (DM)
ES: O/O adults at risk for T2DM


2.5 to 5.5kg weight loss at > 2 years achieved w/
lifestyle intervention (+/- orlistat) reduced risk of
developing T2DM by 30-60%
ES: O/O adults with T2DM
2 to 5% weight loss in 1-4 years (lifestyle +/- orlistat)
lowered HgbA1c by 0.2-0.3%
 5-10% weight loss at 1 year (lifestyle +/- orlistat)
associated with HgbA1c reductions of 0.6-1% and ↓
DM medications

Strength of Evidence: High
CQ1(DM)-MORTALITY
ES: O/O adults with T2DM

Intentional weight loss of 9 to13 kg had a 25%
decrease in mortality rate vs. weight stable controls

Observational cohort studies
Strength of Evidence: Low
CQ1(LIPID)
 Weight
loss and impact on lipid profiles
ES: O/O adults +/- elevated CVD risk

Dose-response relationship between amount of
weight loss (lifestyle) and the improvement in lipid
profile
 Weight loss
<3 kg: more modest/variable improvements in
triglycerides (TG) , high-density lipoprotein (HDL)
cholesterol, and low-density lipoprotein (LDL) cholesterol
 3kg: decrease TG at least 15 mg/dL
 5 kg to 8 kg
 Decrease LDL by ~5 mg/dL
 Increase HDL by 2 to 3 mg/dL

Strength of evidence: High
CQ1(HTN)
 Weight
loss and hypertension (HTN) risk
ES: O/O adults with +CVD risk (including
T2DM/HTN)

Dose-response relationship between the amount of
weight loss achieved at up to 3 years (lifestyle +/orlistat) and the lowering of blood pressure (BP)
 5% weight loss: mean reduction observed
3 mm Hg systolic BP
 2 mm Hg diastolic BP


<5% weight loss: more modest/variable BP reductions
Strength of evidence: High
SUMMARY-CQ1

Counsel O/O adults with CV risk factors
that lifestyle changes that produce even
modest, sustained weight loss of 3%-5%
produce clinically meaningful health
benefits

Greater weight losses = greater benefits


NHLBI grade: A (strong)
ACC/AHA: IA
CRITICAL QUESTION 2 (CQ2)
• Are the current BMI cutpoint values for O/O vs. normal
associated with ↑ CVD risk?
• Are the current waist circumference cutpoints associated
with ↑ CVD risk? How do they compare**
• Are differences across population subgroups (in relation to
BMI/waist circumference and ↑ CVD risk/mortality)
sufficiently large to warrant different cutpoints? **
• What are the associations between maintaining weight
and weight gain with ↑ CVD risk in normal weight,
overweight, and obese adults?**
**Not enough evidence to answer
CLASSIFICATION OF OVERWEIGHT AND OBESITY
BY BMI, WAIST CIRCUMFERENCE AND ASSOCIATED
DISEASE RISK*
Disease Risk* Relative to Normal
Weight and Waist Circumference
BMI (kg/m2)
Obesity
Class
Men: < 102 cm (< 40 in)
Women: < 88 cm (< 35 in)
> 102 cm (> 40 in)
> 88 cm (> 35 in)
Underweight
<18.5
—
—
Normal
18.5 –24.9
—
—
Overweight 25.0 – 29.9
Obesity
Extreme
Obesity
Increased
High
30.0 – 34.9
I
High
Very High
35.0 – 39.9
II
Very High
Very High
> 40
III
Extremely High
Extremely
High
* Disease risk for T2DM, HTN, and CVD
NIH, NHLBI. Clinical Guidelines on the identification, evaluation, and treatment of overweight and obesity in Adults. The
evidence report. NIH Publication No. 98-4083, 1998.
CRITICAL QUESTION 2 (CQ2)
ES: Current BMI cutpoint - O/O vs. normal
Associated with ↑ risk of combined fatal and nonfatal
coronary heart disease (CHD)
 Associated with ↑ risk of fatal CHD in both sexes

ES: All-cause mortality

The current category for overweight


NOT associated with ↑ risk of all-cause mortality
BMI at or above the current cutpoint for obesity

IS associated with an ↑ risk of all-cause mortality vs.
normal weight
Strength of Evidence: Moderate
SUMMARY-CQ2
(IDENTIFY PATIENTS WHO NEED TO LOSE WEIGHT)

Calculate BMI at least annually
NHLBI grade: expert opinion
 ACC/AHA: IC


Use current cutpoints:
For O/O to identify adults who may be at ↑risk of CVD
 Obesity to identify adults who may be at ↑ risk of
mortality from all causes

NHLBI grade: A (strong)
 ACC/AHA: IB

SUMMARY CQ2
(IDENTIFY PATIENTS WHO NEED TO LOSE WEIGHT)

Advise O/O adults that greater BMI= greater risk
of CVD, T2DM, and all-cause mortality
NHLBI grade: A (strong)
 ACC/AHA: IB


Measure waist circumference at annual visits or
more frequently in O/O adults

Greater waist circumference= greater risk of CVD,
T2DM, and all-cause mortality
NHLBI grade: expert opinion
 ACC/AHA: IIB

CRITICAL QUESTION 3 (CQ3)
• During weight loss or weight
maintenance after weight loss, what are
the comparative health benefits or harms
of the above diets and other dietary
weight loss strategies?
• In O/O adults, what is the comparative
efficacy/effectiveness of diets of differing
forms and structures OR other dietary
weight loss strategies in achieving or
maintaining weight loss?
SUMMARY: CQ3
(DIETS FOR WEIGHT LOSS)
 Prescribe
a diet to achieve reduced calorie
intake for O/O individuals who would
benefit from weight loss, as part of a
comprehensive lifestyle intervention.

Prescribing options:
1,200–1,500
kcal/d for
women &
1,500–1,800
kcal/d for men
500 kcal/day
or
750 kcal/day
energy
deficit
Evidencebased diet
that restricts
certain food
types
NHLBI grade: A (strong)
ACC/AHA: IB
SUMMARY: CQ3
(DIETS FOR WEIGHT LOSS)

Prescribe a calorie-restricted diet, for O/O
individuals based on the patient’s preferences
and health status and preferably refer to a
nutrition professional for counseling

Variety of dietary approaches = weight loss
NHLBI grade: A (strong)
 ACC/AHA: IB

CRITICAL QUESTION 4 (CQ4)
• Among O/O adults, what is the efficacy/effectiveness of
a comprehensive lifestyle intervention program (CLIP)
in facilitating weight loss or maintenance of lost
weight?
• What characteristics of delivering comprehensive
lifestyle interventions are associated with greater
weight loss or weight loss maintenance?
• Frequency and duration of treatment
• Individual vs. group sessions
• Onsite vs. telephone/email contact
CRITICAL QUESTION 4 (CQ4)

ES: The principal components of an effective
high-intensity, on-site CLIP include
Reduced
calorie
diet
•Physical activity >150
min/week
•200-300 min/week to
maintain/minimize
gain
Increased
physical
activity
Behavioral
therapy
Strength of evidence: High
•Food intake
•Physical activity
•Weight
SUMMARY CQ4
(LIFESTYLE INTERVENTION AND COUNSELING)

Advise O/O
individuals to
participate for ≥6
months in a CLIP that
assists participants in
adhering to the
principal components
NHLBI grade: A
(strong)
 ACC/AHA: IA


Prescribe on site,
high-intensity CLIP in
individual or group
sessions by a trained
interventionist (TI)†
NHLBI grade: A
(strong)
 ACC/AHA: IB

† Trained internationalist (reviewed studies) included mostly health professionals (ie. RN,
psychologist, exercise specialists, or health counselors).
SUMMARY CQ4
(LIFESTYLE INTERVENTION AND COUNSELING)

Electronically
delivered weight loss
programs (+ telephone) that
include personalized
feedback from TI can
be prescribed but may
result in smaller
weight loss vs. face-toface
NHLBI grade: B
(moderate)
 ACC/AHA: IIaA


Some commercialbased programs that
provide a CLIP can be
prescribed, provided
there is peer-reviewed
published evidence of
safety and efficacy
NHLBI grade: B
(moderate)
 ACC/AHA: IIaA

SUMMARY CQ4
(LIFESTYLE INTERVENTION AND COUNSELING)

Use a very low calorie diet (defined as <800
kcal/day)
ONLY in limited circumstances
 ONLY when provided by trained practitioners in a
medical care setting
 Medical supervision required (more discussion ahead)

NHLBI grade: A (strong)
 ACC/AHA: IIA


Advise O/O individuals who have lost weight to
participate long-term (≥1 year) in a CLIP
NHLBI grade: A (strong)
 ACC/AHA: IA

SUMMARY CQ4
(LIFESTYLE INTERVENTION AND COUNSELING)

For weight loss MAINTENANCE
Prescribe face-to-face or programs that provide
regular contact (> monthly)
 With a trained interventionist who

Engage in high levels of physical activity
 200-300 minutes/week
 Monitor body weight regularly
 Weekly or more frequent
 Consume a reduced-calorie diet (maintain lower body wt)



NHLBI grade: A (strong)
ACC/AHA: IA
COMPREHENSIVE LIFESTYLE +
MEDICALLY SUPERVISED PROGRAMS

Veteran’s Administration

MOVE!(Managing Overweight and/or Obesity for
Veterans Everywhere).
Evidence-based weight management program
 Largest/most comprehensive weight management program
 Individual, group, and activity sessions


MOVE! Intensive

Designed extreme obesity who have NOT been successful in
MOVE!
MOVE! INTENSIVE
12 day on-site program focus: diet, exercise and
behavior
 Criteria


BMI >35 w/ comorbid conditions or BMI >40


Failure to achieve/maintain a 5-10% weight loss with
standard MOVE!
Must be
Independent with all ADL’s
 Able to walk 100 feet unassisted
 Willing to complete health appraisal and sign behavioral
agreement

MOVE! INTENSIVE

Team







Dietician
Nurse practitioner
Pharmacist
Physical therapist
Behavioral
psychologist
Recreational therapist
Chaplain

Clearance by primary
care provider (PCP) +/





Mental health
Cardiac
Pulmonary
Hematology
GI/liver
Nephrology, etc
MOVE! INTENSIVE
Medication adjustments
Diabetes
Blood Pressure
Additions
•Discontinue
•Short acting insulin
•Orals causing
hypoglycemia
•Cut in half
•Intermediate, longacting insulin
•Continue/adjust
•Metformin/DPP-4
•Case-by-case
•GLP-1/TZDs
•ACE/ARB
•Multi-vitamin
•Discontinue
•Constipation
•Diuretics
•Non-rx
•Discontinued
•Reduced in HF or excess
fluid
MOVE! INTENSIVE
Diet
•800 calorie diet
•Cooking
•Shopping
Exercise
•Two 1-hour gym sessions
daily
•Walking
•Tai Chi
•Wii fitness
Behavior
•Journaling (sleep,
emotions, etc.)
•Food Records
•Blood pressure/blood
sugar records
•Group & individual
therapy
•Health assessment
•Goal setting
MOVE! INTENSIVE
WEEK 1
MONDAY
6:00 AM
6:30 AM
7:00 AM
Breakfast
7:30 AM
8:00 AM
TUESDAY
FRIDAY
SATURDAY
SUNDAY
Weigh In
Walk/Wheel
Weigh In
Walk/Wheel
Weigh In
Walk/Wheel
Weigh In
Walk/Wheel
Weigh In
Walk/Wheel
Weigh In
Walk/Wheel
Breakfast
Journaling
Breakfast
Journaling
Breakfast
Journaling
Breakfast
Journaling
Breakfast
Journaling
Breakfast
Journaling
Wii Games
Wii Games
Orientation CLC Fitness Center
WEDNESDAY THURSDAY
Fitness Center Fitness Center Fitness Center
8:30 AM
9:00 AM
9:30 AM
Behavior
Change
Counseling CLC1
DR
10:00 AM
Physical Therapy
10:30 AM
11:00 AM
11:30 AM
12:00 PM
Wii Games
Educational
DVD
Behavior Change
Counseling CLC1
DR
Educational DVD
(room)
Diet Preview
(room)
Pharmacy
Review
Lunch
Supersize Me
Lunch
CLC1 DR
Lunch
Nutrition ClassPortion
Educational
DVD
Chaplain
Nutrition
Class:
Grocery
Shopping
Tour
Behavior
Fitness Center
Change
Counseling CLC1
DR
Wii Games
Free Time
Fitness Center
Free Time
Healthy Shopping
Health Class
Free Time
MOVE
Support
Group ( rm
2315)
Lunch
Free Time
Free Time
Educational DVD Educational DVD
Enjoy Nutrition (1)
Food Matters
Lunch
Lunch
Lunch
Menu Planning
Wii Games
Wii Games
Fitness Center
Free Time
12:30 PM
1:00 PM
1:30 PM
2:00 PM
2:30 PM
3:00 PM
3:30 PM
Control/Label Reading Overweight &
CLC1 DR
Obesity
Fitness Center Fitness Center
Orientation
CLC2
Dexascan
Free Time
4th floor Molly
4:00 PM
Home Exercise
Chapel
Fitness Center Fitness Center Fitness Center
MyHealtheVet
Educational
DVD
Class (CLC 1)
Forks over
Knives
Tai Chi (rm 2315)
Tai Chi (rm
2315)
4:30 PM
Video /Walk
5:00 PM
Supper
Supper
Free Time
Educational DVD
Tai Chi CLC2
Enjoy Nutrition (2)
Home Exercise
Free Time
dining room
Free Time
Video /Walk
Supper
Supper
6:00 PM
Walking
8:00 PM
Journaling
Walking
Journaling
Walking
Journaling
9:00 PM
Snack
Snack
Snack
Supper
Supper
Walking
Journaling
Supper
Walking
Journaling
Walking
Journaling
Walking
Journaling
Snack
Snack
Snack
Snack
MOVE! INTENSIVE

Discharge
1200 calorie diet
 Group or individual classes (dietician)
 With most current medication adjustments


Follow-up within 2 weeks clinical pharmacist/PCP
MOVE! INTENSIVE
Data (8/2012-4/2014)
Average BMI: 42.41

Average MOVE! IOP % Body Weight Lost
8
7
% Body Weight Lost

6
5
4
3
2
6.94
4.94
6.38
5.76
5.56
5.53
4.82
1
0
Post-IOP (n=104) 1 month (n=94) 3 month (n=83) 6 month (n=81) 9 month (n=55) 12 month (n=65) 18 month (n=15)
Time
PHARMACOLOGY
Withdrawn…

Fenfluramine (Pondimin,1973)

Dexfenfluramine (Redux, 1996)

Provider-initiated reports of
valvular heart disease

Still hanging on…

Diethylpropion HCL and ER
(Tenuate, 1960)


Withdrawn September 1997

Off-label use of “Fen-phen”
Indication (C-IV)

Contraindications (CI)


Sibutramine (Meridia,1997)
 SCOUT trial: 16% ↑ in risk
of major adverse CV events

Withdrawn: October 2010
Short-term adjunct (diet) for
weight loss







Pulmonary HTN
Advanced arteriosclerosis
Hyperthyroidism
Glaucoma
Severe HTN
Agitated states
History drug abuse
MAOI within 14 days
PHARMACOLOGY
Still hanging on…

Phentermine (Adipex-P, 1959)

Indication (C-IV)



Orlistat (Alli, Xenical, 1999)







CVD (uncontrolled HTN, CVA,
arrhythmias, CHF)
Hyperthyroidism
Glaucoma
Agitated states
History of drug abuse
MAOI within 14 days
Pregnancy/lactation
Drug interaction (DI)

SSRI: coadministration NOT
recommended
Indication


CI


Short-term adjunct
(exercise/diet/behavior) for
weight loss
Still hanging on…

CI





Weight loss AND maintenance
with diet
Reduce the risk for weight
regain after prior weight loss
Pregnancy
Chronic malabsorption
syndrome
Cholestasis
MVI indicated +/- 2hrs of dose
DI: levothyroxine (+/- 4hrs)
cyclosporine (3hrs after)
PHARMACOLOGY:
THE NEW KIDS ON THE BLOCK
Phentermine/Topiramate
(Qsymia)
Locaserin (Belviq)
PHENTERMINE/TOPIRAMATE (QSYMIA)
THE HISTORY...
2008 reports: providers writing phentermine in
am + topiramate bedtime
 New Drug Application (NDA) 12/2009
phentermine/topiramate (Qnexa)
 July 2010 reviewed by FDA committee



No efficacy issues cited
2 safety concerns
Teratogenic potential
 Detailed plan/strategy to evaluate and mitigate risk
 Provide evidence that ↑heart rate (hr), 0.6 to 1.6 beats/min
(bpm), does not increase the risk for major adverse
cardiovascular events (MACE)
 Results from SEQUEL

PHENTERMINE/TOPIRAMATE (QSYMIA)
THE HISTORY...

SEQUEL


1-year extension study to look at a second year of
exposure of obese subjects with obesity-related
comorbidities
676 subjects enrolled


Mean exposure: 728.5 days
Results
1.6 bpm ↑hr (high dose) + 5.2 mmHg decrease in systolic
BP (SBP)
 Clinical relevance unknown (1−2 bpm increase in HR)
 NO increase in MACE composite hazard ratios vs. placebo


Approved July 2012
10 postmarketing studies mandated
 Potential name confusion

PHENTERMINE/TOPIRAMATE (QSYMIA)

Indication (C-IV)


Adjunct (diet/exercise)
for chronic weight
management with BMI
>30 or 27+ comorbidity
Dose titration
< 3% not achieved: ↑ dose
 < 5% not achieved: d/c


CI
Pregnancy
 MAOI within 14 days
 Glaucoma
 Hyperthyroidism

Caution/Consideration

Cardiac/CV disease








Not studied in HF
Excluded
stroke/MI/unstable CV
disease in previous 6 mo.
Elderly: >65 y.o. only 7%
of subjects
On topiramate
Oral carbonic anhydrase
inhibitor (avoid use)
CNS effects
Renal/hepatic
impairment
PHENTERMINE/TOPIRAMATE (QSYMIA)

Safety

The FDA-approved REMS program
 Purpose
 Increase awareness of congenital malformations
 Prescriber Requirements




Pharmacy Requirements





Encouraged to undergo the training
Counsel women of childbearing potential
Fax/mail universal form + prescription to certified pharmacy
Certified to dispense
Staff must receive training
Medication guide + risk of birth defects brochure
Maintain a list of prescribers
Monitoring

BP, glucose, blood chemistry, mood
LOCASERIN (BELVIQ)
THE HISTORY…

NDA December 2009
2 completed Phase III trials in non-diabetic (>7000 pts)
 Phase III trial (BLOOM-DM) was ongoing


October 2010 FDA responded siting 4 main
issues + updated safety (particularly valvulopathy)
Mammary tumor findings in female rats
 Astrocytoma in male rats
 A request to include data from BLOOM-DM
 Assessment of abuse potential (2 rodent experiments)

LOCASERIN (BELVIQ)
THE HISTORY…

April 2012 briefing document submitted to FDA

Mammary tumor


Astrocytoma


Pathology work group established tumor related to high
dose (24x human exposure)
Extrapolated data: exposure in rat brain at dose level
revealing NO astrocytoma was ~70x estimated level that
10mg bid would produce
Abuse potential


Repeated animal studies
Package insert
 Human abuse potential study in recreational drug abusers,
doses of lorcaserin (40 and 60 mg)
 2- to 6-fold increases on measures of “High”, “Good Drug
Effects”, “Hallucinations” and “Sedation” vs. placebo
 Similar to those produced by zolpidem and ketamine
LOCASERIN (BELVIQ)
THE HISTORY…

Briefing (continued)

Safety update (valvulopathy)
BLOOM
Valvulopathy, n (%)
Rel. Risk (95% CI)
BLOSSOM
Lorcaserin
n=1278
Placebo
n=1191
Lorcaserin
n=1208
Placebo
n=1153
Lorcaserin
n=210
Placebo
n=209
34 (2.7)
28 (2.4)
24 (2.0)
23 (2.0)
6 (2.9)
1 (0.5)
1.13 (0.69, 1.85)
Pooled Rel. Risk

1.00 (0.57, 1.75)
1.16 (0.81, 1.67)
Approved June 2012

BLOOM-DM
6 postmarketing studies mandated
5.97 (0.73, 49.17)
LOCASERIN (BELVIQ)

Mechanism of action: serotonin 2C receptor
agonist


Indication (C-IV)


Believed to decrease food consumption and promote
satiety
Adjunct (diet/exercise) for chronic weight
management with BMI >30 or 27+ comorbidity
Dose: 10 mg twice daily (max)

5% of baseline body weight not lost by week 12 =
discontinue
LOCASERIN (BELVIQ)

CI



Pregnancy
DI
SSRI/SNRI excluded
 2D6 substrate caution


Safety


No REMS
Monitoring

BP, glucose, mood
Caution/Consideration
Serotonin syndrome or
neuroleptic malignant
syndrome
 Valvular heart disease


Not studied CHF
Cognitive impairment;
psychiatric disorders
 Priapism
 Elderly (2.5% >65 y.o.
studied)

HOW DO THEY STACK UP?
10
9
8
diethylpropion
7
phentermine
6
orlistat
5
lorcaserin
4
lorcaserin2
3
Qsymia 7.5/46
2
Qsymia 15/92
1
0
kg weight loss more than placebo
CASE 1

MK is a 32 y.o. hispanic female with body mass
index (BMI) of 33. She has a diagnosis of
hypertension (HTN) and hypothyroidism. She
discusses her and her spouse’s desire to become
pregnant within the next year and her
frustrations with her current weight. She reports
trying really hard at home without success.
What is your recommendation?
A. phenteramine/topiramate (Qsymia)
B. diethylpropion
C. a comprehensive lifestyle intervention
program
D. bariatric surgery
QUESTIONS?
REFERENCES
1.
Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl
J Med 2010;363:245-56.
2.
O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2
diabetes mellitus: The BLOOM-DM study. Obesity 2012;20:1426-36.
3.
Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults:
The BLOSSOM trial. J Clin Endocrinol Metab 2011;96:3067-77.
4.
BELVIQ (lorcaserin hydrochloride) package insert. June 2012.
5.
Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532-46.
6.
Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized
control trial (EQUIP). Obesity 2011;20:330-42.
7.
Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on
weight and associated comorbidities in overweight and obese adults (CONQUER): a randomized, placebo-controlled, phase 3
trial. Lancet 2011;377:1341-52.
8.
Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release
phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study.
Am J Clin Nutr 2012;95:297-308.
9.
Jensen MD, Ryan DH, Apovian CM, et. al. Circulation. 2013 Nov 12. 2013 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.
10.
FDA. FDA Briefing Document
http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm179871.htm (Accessed 30
Apr 2014)
11.
FDA. FDA Briefing Document
http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisory
committee/ucm293908.pdf (Accessed 30 Apr 2014)
12.
Micromedex. [Internet]. Greenwood Village: Truven Health Analytics. [cited 2014 Apr 30]. Available from:
http://www.micromedexsolutions.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/81F8F6/ND_AppPro
duct/evidencexpert/DUPLICATIONSHIELDSYNC/0E5775/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFA
ctionId/pf.HomePage