1. 1
Treatment of Obese Patients with Comorbidities
Medication MOA Efficacy Dosing Adverse Effects
Diabetes Mellitus
Metformin -Biguanide: reduces
hepatic glucose
production, decreases
intestinal glucose
absorption from the
GI tract, and enhances
insulin sensitivity
- Diabetes Prevention
Program (double-blind
placebo controlled): loss
at 2.8 years metformin
group 2.9 kg vs. placebo
group 1.04 kg
- Weight loss is directly
related to adherence
-Weight loss persisted
during the eight year
follow up period in the
most adherent patients
-Initiate 500 mg QD-
BID
-Titrate by 500 mg/day
weekly
-Max dose 2,550 mg/day
-Max effective dose in
diabetes 2,000 mg/day
-Diarrhea
-Nausea and
vomiting
Pramlintide -Synthetic form of
amylin
-Reduces caloric
intake through
centrally-mediated
appetite suppression
- A six month clinical
trial showed additive
weight loss when
added to phentermine.
-Initiate 60 mcg SC
immediately prior to
major meals
-Increase dose to 120
mcg after 3 days
-Decrease dose to 60
mcg with severe nausea
-Nausea
-Hypoglycemia
-Anorexia
Byetta (exenatide) -Glucagon-like
peptide-1 receptor
agonist
-Slows gastric
emptying
-Decreases food intake by
19%
-Systematic review showed
a weight loss of 2.37 kg for
all GLP-1 agonists
-1.44 kg vs.placebo; 4.76
kg vs.insulin
-26 week randomized
control trial resulted in
weight loss of 2.3 kg for the
exenatide group vs.a 1.8 kg
gain in insulin glargine
group.
Immediate Release
-Initiate 5 mcg BID 60
min prior to meals
-Increase to 10 mcg BID
based on diabetic
response
Extended Release
-2 mg once weekly
-Headache
-Nausea and
vomiting

2. 2
Victoza (liraglutide)
Saxenda (liraglutide)
-Glucagon-like
peptide-1 receptor
agonist
-Saxenda is FDA
approved for weight
loss
-20 week European
trial evaluated various
daily doses and weight
loss effect: 1.2 mg (4.8
kg), 1.8 mg (5.5 kg),
2.4 mg (6.3 kg), 3.0
mg (7.2 kg) vs. 2.8 kg
in the placebo group
vs. 4.1 kg in the orlistat
group
-76% of 3.0 mg
treatment group
achieved >5% weight
loss
Chronic Weight
Management:
-Initiate 0.6 mg SC QD
for one week
-Increase dose by 0.6 mg
weekly to a target 3.0
mg
Diabetes Treatment:
-Initiate 0.6 mg SC QD
for one week
-Increase to 1.2 mg QD
-Max 1.8 mg QD
-Headache
-Nausea and
vomiting
Depression, Epilepsy, Migraine
Bupropion
-Inhibitor of
norepinephrine and
dopamine reuptake
-Reduces food intake
by acting on
adrenergic and
dopaminergic
receptors in the
hypothalamus
-Reduced body weight
by 6.2% (300 mg/day)
and 7.2% (400
mg/day)
-Dose varies based on
comorbidity and salt
form
-Tachycardia
-Headache
-Agitation
Topiramate
-Reduces appetite by
enhancing GABA
activity
-n=385 patients
randomized to five
groups (64 mg/d, 96
mg/d, 192 mg/d, 384
mg/day, or placebo)
resulted in weight loss
of 7.3% of initial
weight at six months
-Weight loss is dose
related
-Dose varies based on
comorbidity
-Used in combination
with phentermine for
weight loss:
Phentermine/Topiramate
3.75/23 mg (initial),
7.5/46 mg
(recommended), 15/92
mg (max)
-Paresthesias
-Somnolence
-Difficulty with
concentration,
memory, and
attention

3. 3
Current Drugs Approved for Treatment of Obesity
Medication MOA Efficacy Dosing/Monitoring Adverse Effects
Phentermine
-Phentermine is a
sympathomimetic amine
producing CNS
stimulation.
-The mechanism by
which it produces
weight loss is primarily
by appetite suppression.
-First approved by the
FDA in 1959.
-Weight loss at 6 months
with Phentermine 15 mg
was 4.6% of total body
weight (n=756), and 8.1
+/- 3.9 kg at 12 weeks
(n=37).
Short-term:
-15-30 mg PO QD
-18.75 mg PO BID
-37.5 mg PO BID
-Increased blood
pressure
-Increased heart
rate
-Appetite
suppression
-Xerostomia
-Insomia
-Irritability
-Nervousness
Belviq (lorcaserin)
-Selectively targets
and binds to the
serotonin 2c receptors
(agonist), thereby
promoting satiety and
decreased food intake.
BLOOM, BLOSSOM,
BLOOM-DM enrolled
patients with a BMI of
>/= 27. At 48 weeks,
weight loss was ~10 kg
in the lorcaserin group,
and weight
maintenance was
demonstrated versus
placebo.
-HbA1c decreased by
0.9 +/- 0.06, FBG
decreased by 27.4 +/-
2.5 mg/dL.
-10 mg PO BID
-Discontinue at 12
weeks of therapy if only
</= 5% weight loss
-Contraindicated in
pregnancy.
-Monitoring for potential
development of
valvulopathy.
-Nausea
-Dizziness
-Fatigue
-Heart valve
disorder
-Hypoglycemia
-Suicidal ideation
-Serotonin
syndrome when
used with SSRIs
or MAOIs

4. 4
Qsymia (phentermine/
topiramate ER)
-Dual mechanism of
appetite
suppression/decreased
food intake, and
increased satiety via
enhanced
catecholamine release.
-EQUIP and
CONQUER trial
reported weight losses
approaching 10%, and
maintained weight loss
of 9.3% below baseline
at the end of two years
at 7.5/46 mg. Patients
taking 15/92 mg
maintained 10.7%
weight loss after two
years.
-Improvements in
cardiovascular risk
factors, such as blood
pressure, triglycerides,
and blood glucose.
- 3.75/23 mg QAM for
14 days, then increase to
7.5/46 mg QD.
-Evaluate weight loss at
12 weeks of therapy, and
discontinue or escalate
the dose if <3% weight
loss.
-To escalate the dose
increase phentermine
dose to 11.25/69 mg for
14 days, then 15/92 mg
for 12 weeks.
-If <5% weight loss,
gradually discontinue.
-Paresthesias
-Dizziness
-Dysgeusia
-Insomnia
-Constipation
-Xerostomia
-Negative
pregnancy test
before and during
treatment, as
topiramate is
associated with a
risk of oral cleft in
the developing
fetus.
Orlistat
(tetrahydrolipstatin)
-Orlistat is a selective
inhibitor of lipases in
the stomach and
intestines that
ultimately reduces the
intestinal digestion of
fat.
-539 adolescents
received 120 mg TID
with a mean net weight
loss -2.87 kg (-3.21 to -
2.53) 95% CI.
-120 mg PO TID
(prescription)
-60 mg PO TID (OTC)
-Recommended to eat a
balanced diet containing
at least 30% calories
from fat.
-Fecalfat loss and
increased urge to
defecate
-Small decreases in
fat soluble vitamins
-Rare cases of
idiosyncratic liver
injury.
Contrave
(naltrexone/bupropion)
-Reduction of food
intake by inhibiting
the reuptake of
dopamine and
norepinephrine,
increasing firing in the
appetite control
center.
-Weight loss at one
year with this
combination was
intermediate between
Qsymia and Belviq.
-No increase in
cardiovascular events
to date.
-Initial dose escalation,
naltrexone 8 mg/bupropion
90 mg (1 tablet) PO QAM
for week 1; then 1 tablet
twice daily, QAM and
QPM,for week 2; then 2
tablets QAM and 1 tablet
QPM for week 3;
maintenance dose, week 4
and thereafter,2 tablets PO
BID, for a total daily
dosage of naltrexone 32
mg/bupropion 360 mg
- Daily doses greater than
naltrexone 32
mg/bupropion 360 mg not
recommended.
-Assess weight loss at 12
-Increased blood
pressure
-Increased pulse