Transcript Pharmacotherapy - Dr. Moulton

Pharmacotherapy
Obesity Pharmacotherapy Outline
•
•
•
How to apply drug trial data to clinical practice
Principles of obesity medication use in clinical practice
Medications approved for long-term use
–
–
•
Medications approved for short term use
–
–
•
phentermine
others rarely used: mazindol, diethylpropion
Medications for use in special patients
–
–
–
•
sibutramine (Meridia)
orlistat (Xenical)
the depressed obese patient – bupropion (Wellbutrin) and venlafaxine
(Effexor)
type 2 diabetes – metformin , pramlintide (Symlin), exendin-4 (Exenatide)
patients with neuropsychiatric problems - topiramate (Topamax) and
zonisamide (Zonegran)
Medications in development
Applying Pharmacotherapy Trials to
the Practice Setting – 6 Tips
Note
units
Mean responses describe how patients fare on average.
The weight loss curves describe the tempo of weight loss.
The placebo response indicates the strength of the behavioral
approach.
Treatment Month
Mean Change in Weight (%)
1.
2.
3.
0
1
2
3
4
5
6
7
8
9
10
11
12
0
–2
–4
–6
–8
Note
plateau
Placebo response
indicates behavioral
program
Placebo
Drug
Applying Pharmacotherapy Trials to
the Practice Setting – 6 Tips
4.
Categorical responses indicate the chance an individual patient
has of meeting key response levels, 5% and 10%.
Significance levels and n’s are important.
5.
†
80
†
†
70
Placebo (n=87)
Drug (n)
†
60
Patients (%)
Chances of
response
50
†
40
*
†
†
30
†
20
1 mg (95)
5 mg (107)
10 mg (99)
15 mg (98)
20 mg (96)
30 mg (101)
*
10
0
5% Responders
*P < 0.01 vs placebo
†P < 0.001 vs placebo
10% Responders
note
Applying Pharmacotherapy Trials to
the Practice Setting – 6 Tips
6. There is no placebo effect in weight loss studies. The placebo represents the
effect of the behavioral intervention.
Study
or Subcategory
WMD (Random)
95% CI
Author 1, 1998*
Author 2, 1998
Author 3, 1999
Author 4, 2000
Author 5, 2000
Author 6, 2000
Author 7, 2000
Author 8, 2002
Author 9, 2002
Total (95% CI)
-10
-5
0
5
10
Metanalyses use placebo-subtracted weight loss and demonstrate the
effect of the medication independent of behavioral intervention.
Principles of Obesity Medication Use
•
Lifestyle interventions are the foundation of medicating for obesity
•
The behavioral approach should be implemented with knowledge of
the medication’s mechanism of action
–
–
Orlistat with 30% fat diet
Sibutramine with meal plan that takes advantage of its satiety
promotion
•
Obesity medications do not cure obesity, just as antihypertensives
do not cure hypertension
•
Not all patients respond to a weight loss medication.
–
•
If the drug’s use is not associated with weight loss within four weeks, it
should be stopped
Medications work as long as they are used
–
Weight gain occurs on stopping medications, although there is some
evidence in support of efficacy of intermittent medication
Obesity Pharmacotherapy
Outline
• How to apply drug trial data to clinical practice
• Principles of obesity medication use in clinical practice
• Medications approved for long-term use
–
–
sibutramine (Meridia)
orlistat (Xenical)
• Medications approved for short term use
–
–
phentermine
others rarely used: mazindol, diethylpropion
• Medications for use in special patients
–
–
–
the depressed obese patient – bupropion (Wellbutrin) and
venlafaxine (Effexor)
type 2 diabetes – metformin , pramlintide (Symlin), exendin-4
(Exenatide)
patients with neuropsychiatric problems - topiramate (Topamax)
and zonisamide (Zonegran)
• Medications in development
Antiobesity Drugs Approved for
Long-Term Use: How They Work
Sibutramine
Orlistat
• FDA approved 1997
• FDA approved 1999
• Induces feeling of satiety
• Reduces absorption of
~30% dietary fat
– Less preoccupation, feeling
satisfied with less food
– Greater control of food
intake
– Need to monitor BP early in
program
• Once daily with or without
food
– Fat in diet passes
undigested
– Facilitates weight loss
– GI side effects
• 3 times daily with meals
and a vitamin supplement
recommended
Mechanisms of Action
Sibutramine’s Active Metabolites Block
Serotonin and Norepinephrine Reuptake
S
S
Reuptake
S
Serotonin
S = sibutramine
 = norepinephrine
 = serotonin
S
S
Reuptake
Norepinephrine
S
Ryan DH et al. Obes Res. 1995;3(suppl 4):553S.
Other SNRIs
• Venlafaxine (Effexor)
– Widely used in depression
– Similar side effect profile to sibutramine, small blood
pressure increases
– Produces some weight loss
Rudolph RL, Derivan AT. J Clin Psychopharmacol. 1996;16(suppl 2):54S.
Sibutramine Key Facts
• Multiple large clinical trials demonstrating:
− Dose-related weight loss occurs for 6 months
− Amount of weight loss related to intensity of behavioral
approach
− Efficacy in weight loss maintenance demonstrated ≥ 2
years
− Weight loss produces benefits in lipids, body composition
and is associated with mean blood pressure decrease
− Trials in patients with hypertension and diabetes
• Favorable side effect profile:
− No abuse potential
− No valvuloplasty, no PPH
• Cautions
− Blood pressure should be monitored
− Should not use with MAOIs, erythromycin, ketoconazole
Sibutramine Produces DoseRelated Weight Loss
Mean Weight Change (lb)
0
Placebo (n = 84)
Sibutramine, mg (n)
1 (92)
–5
*
–10
*
*
*
*
–15
–20
0
3
6
9
12
15
18
21
5 (103)
10 (95)
Approved
dose
range
15 (94)
20 (89)
30 (96)
24
Week
Bray GA et al. Obes Res. 1999;7:189.
**10 and 15 mg are recommended doses
The Amount of Weight Loss with
Sibutramine Is Related to the Intensity
of the Behavioral Intervention*
% Weight Change at 6 months
0
Sibutramine
Sibutramine
+ Group
Sessions
Sibutramine
+ Group Sessions
+ Meal
Replacements
-2
-4
-6
-5.2
-8
-10
-12
-11.5
-14
-16
-18
-20
* Weight loss at 6 months
Wadden TA et al. Arch Intern Med 2001;161:218-227.
-17.1
STORM: 77% (ITT) Achieved > 5%
Weight Loss at Six Months
Weight Loss
230
Weight Maintenance
Body Weight (lb)
Placebo
225
220
215
210
205
200
Sibutramine
195
0
2
4
6
8
10 12 14 16 18 20 22 24
Month
*Same diet, exercise for sibutramine, placebo;
P  0.001, sibutramine vs placebo for weight maintenance
James WPT et al. Lancet. 2000;356:2119.
STORM: Sibutramine Promotes
Weight Loss Maintenance*
Weight Loss
230
Weight Maintenance
Body Weight (lb)
Placebo
225
220
215
210
205
200
Sibutramine
195
0
2
4
6
8
10 12 14 16 18 20 22 24
Month
*Same diet, exercise for sibutramine, placebo;
P  0.001, sibutramine vs placebo for weight maintenance
James WPT et al. Lancet. 2000;356:2119.
Following VLCD, Sibutramine
Promotes Additional Weight Loss and
Weight Loss Maintenance
Mean Weight (lb)
233
229
224
220
217
211
207
202
Placebo
198
194
–1
Sibutramine
0
1
2
3
4
5
6
7
8
9
10 11 12
Treatment Month
P < 0.001 for months 1 to 12, sibutramine vs placebo
= very low calorie diet (VLCD)
Adapted with permission from Apfelbaum M et al. Am J Med. 1999;106:179.
Three Sibutramine Studies
Percent Achieving Meaningful Weight Loss
84
% Achieving Weight Loss
90
80
≥ 5%
≥ 10%
67
67
70
54
60
50
40
63
35
30
20
10
0
1Bray
6 months
treatment
1
12 months
treatment 2
GA et al. Obes Res. 1999;7:189.
M et al. Am J Med. 1999;106:179.
3James WPT et al. Lancet 2000;356:2119-2125.
2Apfelbaum
24 months
treatment 3
P  0.001 vs placebo
Weight Loss with Sibutramine Is Associated
with Improvements in Lipids
(STORM Data)
5
Triglycerides
5
0
VLDL-Cholesterol
0
Placebo
–5
% Change
% Change
–5
–10
†

–15

*

*

–10

–15
Sibutramine
*

–20


‡
§







–20
Placebo
Sibutramine
–25
–25
0
6
12
18
Month Assessed
24
0
25
6
HDL-Cholesterol
*

20
% Change

Weight loss = months 1–6;
Weight maintenance = months 7–24;
*P < 0.001; †P = 0.002; ‡P = 0.005;
§P = 0.001 vs placebo
12
18
Month Assessed
*



15
Placebo
10
5


Adapted with permission from James WPT
et al. Lancet. 2000;356:2119.
Sibutramine
0
0
6
12
18
Month Assessed
24
24
Weight Loss with Sibutramine Is Associated with
Improvement in Waist Circumference
(STORM data)
Waist Circumference (in.)
44
43
Placebo
42
41
40
Sibutramine
39
38
0
2
4
6
8
10
12
14
16
18
20
22
Month
NB: Same diet and exercise for both sibutramine and placebo
James WPT et al. Lancet. 2000;356:2119.
24
Sibutramine and Blood Pressure
•
Labeling instructions:
Warning.
Blood pressure and pulse. MERIDIA SUBSTANTIALLY
INCREASES BLOOD PRESSURE IN SOME PATIENTS.
REGULAR MONITORING OF BLOOD PRESSURE IS
REQUIRED WHEN PRESCRIBING MERIDIA. In placebocontrolled obesity studies, MERIDIA 5 to 20 mg once daily was
associated with mean increases in systolic and diastolic blood
pressure of approximately 1 to 3 mg relative to placebo…
Dose Related Effects of Sibutramine
on Systolic Blood Pressure (SBP)
Placebo
Change in SBP (mmHg)
10
n=1944
Sibutramine
Sibutramine Sibutramine
Sibutramine
n=1318
n=1924
n=128
10 mg
15 mg
20 mg
n=1126
30 mg
8
6
+3.8
4
+2.6
+1.0
2
0
-1
-0.1
Data on file, Abbott Laboratories.
-0.1
*
*
*
* p < 0.05 compared
to placebo
Maximum BP Changes vs. Baseline
30
Post hoc analysis of 21 randomized placebo controlled trials of ≥ 12 weeks duration
3419 overweight and obese patients with normal or controlled blood pressure
Sibutramine 10-15 mg n=1898; placebo n= 1521
Control (n=1,521)
Sibutramine (n=1,898)
Patients (%)
25
20
15
10
5
0
No
> 0 – < 5 5 – < 10 10 – < 15 15 – < 20 20 – < 25 25 – < 30 30 – < 35 35 – < 40
increase
SBP or DBP increase (mmHg)
Adapted from Sharma AM et al. NAASO 2003.
> 40
STORM: Change in Vital Signs
Baseline to 24 Months in
Sibutramine Treatment Group
Mean Change
BP, mm HG
Systolic
Diastolic
Pulse rate (bpm)
Sibutramine
Placebo
0.1
2.3
4.1
- 4.7
- 1.6
- 1.9
In STORM most subjects reached 20 mg per study
design
James WPT et al. Lancet. 2000;356:2119.
Blood Pressure is Lowered with
Weight Loss Using Sibutramine
Placebo (n = 2255)
Change in SBP (mmHg)
3
Sibutramine (n = 4536)
2
1
0
22%
78%
53%
6%
23%
47%
-1
-2
-3
-4
% of treatment group
-5
< 5% weight loss
> 5% weight loss
> 10% weight loss
Although weight loss with sibutramine was not associated with equivalent BP reductions as
placebo, a greater proportion of sibutramine treated patients achieved weight loss.
Adapted from Sharma AM, Int J Obes Relat Metab Disord 2001;25 (Suppl 4): S20-S23.
The Reality of Sibutramine’s BP Effects
•
Mean BP changes in recommended dose range is
increase
•
A few, < 5%, have unacceptable blood pressure increases while on
sibutramine
•
Significant weight loss, > 5%, is associated with mean BP decrease
on sibutramine
•
BP effects of sibutramine are blocked by beta blockers1
•
BP effects of sibutramine are blocked by exercise program2
•
In addition to peripheral effects, sibutramine may have central
“clonidine-like” sympatholytic effects1
1.
2.
Birkenfeld AL et al. Circulation 2002;106: 2459-2465
Berube-Parent S et al. IJO 2001;25: 1144-1153
~ 1 mm Hg
Tips for Managing Patients on
Sibutramine
• Start at 10 mg once daily
• Prescribe a sensible diet –
–
–
Meal replacements for two meals and two snacks + one
sensible meal per day
Portion controlled diet with at least three meals per day
• Follow –up:
–
–
4 pounds weight loss in first 4 weeks helps predict success
Monitor blood pressure. Use clinical judgement about
continuing
• Increase dose to increase weight loss, provided BP is
well controlled. Decrease dose or discontinue for BP
concerns
• Stay within recommended dose range of 5 to 15 mg
• Encourage long term use
Antiobesity Drugs Approved for
Long-Term Use: How They Work
Sibutramine
Orlistat
• FDA approved 1997
• FDA approved 1999
• Induces feeling of satiety
• Reduces absorption of
~30% dietary fat
– Less preoccupation, feeling
satisfied with less food
– Greater control of food
intake
– Need to monitor BP early in
program
• Once daily with or without
food
– Fat in diet passes
undigested
– Facilitates weight loss
– GI side effects
• 3 times daily with meals
and a vitamin supplement
recommended
Orlistat Prevents Fat Digestion by
Binding to Gastrointestinal Lipases
Intestinal Lumen
Orlistat
Mucosal Cell
TG
FA
MG
Bile Acids
Micelle
TG=triglyceride; MG=monoglyceride; FA=fatty acid
Orlistat: Key Facts
• Multiple large clinical trials demonstrating
− Weight loss occurs for 6 months
− Efficacy in weight loss maintenance demonstrated
≥ 4 years
− Weight loss produces benefits in glycemic control,
lipids, waist circumference, BP
− Trials in persons with diabetes and hypertension
− Independent action on LDL cholesterol
• Favorable side effect profile
− No abuse potential
− No valvulopathy, no PPH
• Cautions
− Vitamin supplement required for long term use
− May interfere with cyclosporin absorption
• Likely to be available over the counter in 2006
Orlistat: 2-Year Efficacy
60
Placebo + diet
51.6
% of Patients
50
40
Orlistat + diet
36.4
27.3
30
15.4
20
10
0
> 5%
> 10%
% of Weight Lost
Meta-analysis of data derived from 4 clinical trials
Xenical® [package insert]. Nutley, NJ: Roche Laboratories, 1999.
Effect of Long-Term Treatment With
Orlistat (The XENDOS Study)
Weight change (kg)
Completers Data
0
Placebo + lifestyle
Orlistat + lifestyle
(n=557)
(n=853)
-3
-4.1 kg
-6
-6.9 kg
-9
-12
0
52
104
156
208
Week
p < 0.001 vs placebo
Torgerson JS et al, Diabetes Care 2004; 27(1): 155-61.
Change in Plasma
LDL-Cholesterol Concentration
(mmol/L)
Independent Effect of Orlistat on
Plasma LDL-Cholesterol
0.0
-0.1
-0.2
-0.3
-0.4
*
-0.5
*
-0.6
-0.7
*
-0.8
-0.9
Placebo
Orlistat
*P < 0.01 vs placebo
*
-1.0
0–5
10 – 15
> 15
5 – 10
Weight Loss Category (% initial body weight)
Segal et al. FASEB J 1999;13:A873.
Data pooled from 5 trials (N=1773)
Orlistat: Effect on Lipids and Waist
Circumference
Placebo
0
15
-0.5
13
11
-1
-1.5
-1.6
-2
-2.5
-3
-2.6
Waist Circumference
% Change
Change (in)
Orlistat 120 mg TID
12.8
9.3
9
7
5
2.9
3
1
1.34
HDL-C
Xenical® [package insert]. Nutley, NJ: Roche Laboratories, 1999.
TG
Orlistat: Effect on Blood Pressure in
At-Risk Patients
Systolic
(ISH, SBP  140 mm Hg)
mm Hg
Diastolic
(DBP  90 mm Hg)
mm Hg
0
0
-1
-2
-2
-4
-3
Orlistat + diet
-4
-6
Placebo + diet
-5
-8
-6
-7
-10
-8
-12
P = 0.032
Data on File (Ref 038-001).
-9
P = NS
Orlistat: Safety
Adverse Events (AEs) at 1 Year
35
31%
Placebo, n = 340
Orlistat, n = 343
30
25
20%
20
%
18%
15
10%
10
7%
7%
5%
5
3%
1%
0%
0
Fatty/Oily Stool
Increased
Defecation
Oily Spotting
• There is concern about fat-soluble vitamin absorption
Sjöström L et al. Lancet. 1998;352:167.
Fecal Urgency
Fecal
Incontinence
Tips for Managing Patients on
Orlistat
• Discuss potential bowel effects and mechanism with
patient
• Start at 120 mg before each meal
• Prescribe a moderate fat diet –
–
•
•
•
•
Caution patients about high fat meal or snack
Metamucil has been shown to reduce bowel effects
For long term use, prescribe a multivitamin
Orlistat can interfere with cyclosporin absorption
Encourage long term use.
Obesity Pharmacotherapy Outline
• How to apply drug trial data to clinical practice
• Principles of obesity medication use in clinical practice
• Medications approved for long-term use
–
–
sibutramine (Meridia)
orlistat (Xenical)
• Medications approved for short term use
–
–
phentermine
others rarely used: mazindol, diethylpropion
• Medications for use in special patients
–
–
–
the depressed obese patient – bupropion (Wellbutrin) and
venlafaxine (Effexor)
type 2 diabetes – metformin , pramlintide (Symlin), exendin-4
(Exenatide)
patients with neuropsychiatric problems - topiramate (Topamax)
and zonisamide (Zonegran)
• Medications in development
Drugs Approved by FDA for
Short Term Use in Treating Obesity
Generic Name
Trade Names
DEA Schedule
Diethylpropion (1959)
Tenuate
IV
Phentermine (1959)
Adipex-P, Ionamin
IV
Benzphetamine* (1960) Didrex
III
Phendimetrazine (1959) Bontril
III
Methamphetamine
Desoxyn
II
Mazindol* (1973)
Mazanor
IV
Physicians’ Desk reference 59th Edition, 2005.
*not listed in PDR, but available
FDA Approved Drugs for
Short Term Use
• Use of schedule II or III drugs for weight management is
not recommended.
• These agents are sympathomimetic as reflected by the
side effect profile (restlessness, insomnia, increase in
pulse, increase in blood pressure and others).
• Intermittent use is the only means to abide by
prescribing guidelines.
• The medications promote appetite reduction. They
should be used with an energy deficit diet.
• Weight loss with these medications averages 5 - 7%
above placebo.
Weight Loss with Continuous and
Intermittent Phentermine
0
0
5
16
10
15
32
0
4
8
12
16
20
Time in Weeks
Munro JF, et al. Br Med J 1968; 1:352-354.
24
28
32
36
Weight loss (lbs)
Weight loss (kg)
Continuous Phentermine
Alternating Phentermine and Placebo
Continuous Placebo
Obesity Pharmacotherapy Outline
• How to apply drug trial data to clinical practice
• Principles of obesity medication use in clinical practice
• Medications approved for long-term use
–
–
sibutramine (Meridia)
orlistat (Xenical)
• Medications approved for short term use
–
–
phentermine
others rarely used: mazindol, diethylpropion
• Medications for use in special patients
–
–
–
the depressed obese patient – bupropion (Wellbutrin) and
venlafaxine (Effexor)
type 2 diabetes – metformin , pramlintide (Symlin), exendin-4
(Exenatide)
patients with neuropsychiatric problems - topiramate (Topamax)
and zonisamide (Zonegran)
• Medications in development
Medicating the Depressed
Obese Patient
• Many antidepressants produce weight gain
• Antidepressants associated with weight loss:
– Bupropion (Wellbutrin)1
– Venlafaxine (Effexor)2
• Antidepressant associated with initial weight
loss at higher doses, followed by weight regain:
– Fluoxetine (Prozac)3
1. Anderson Obes Res 2002:10:633.
2. PDR Edition 29, 2005.
3. Darga et al, AJCN, 1991.
Treatment with Bupropion
0
Weight loss (%)
Placebo
-5
SR 300
-10
SR 400
-15
0
10
20
30
Weeks of Treatment
Anderson Obes Res 2002:10:633.
40
50
Fluoxetine 60 mg and Weight Loss*
Weight Loss (kg)
0
N = 23
Placebo
-2
-4
N = 16
-6
-8
N = 22
N = 14
-10
Fluoxetine
-12
-14
-16
1 3 5 7 9
13
17
21
29
37
Week number
Darga et al, AJCN, 1991.
45
53
Medicating the Patient with
Type 2 Diabetes
• Weight gain is associated with use of
thioglitazones, sulfonylureas and insulin.
• Metformin is associated with small amounts of
weight loss.
• Pramlintide is associated with weight loss.
Weight Change with Metformin
in DPP Trial
Weight Change (Kg)
+1
Placebo
0
-1
Metformin
-2
-3
-4
0
6
DPP NEJM 2002.
12
18
24
30
36
Months in study
42
48
Pramlintide
• Pramlintide injection approved by FDA 3/2005.
• Indication: as an adjunct treatment in patients with
T1DM or T2DM who use mealtime insulin therapy and
have failed to achieve desired glucose control despite
optimal insulin therapy, with or without a concurrent
sulfonylurea agent and/or metformin.
• Synthetic analog of human amylin, designed to replace
reduced amylin secretion that accompanies beta cell.
• Patients in clinical trials used less mealtime insulin and
also had a reduction in body weight compared to
patients taking insulin alone.
Exenatide
• Exenatide is an incretin mimetic
• Exenatide exhibits many of the same effects
as the human incretin hormone GLP-1
– Improve blood sugar
– Weight loss
• The FDA’s action date for exenatide is
April 30, 2005
Medicating the
Neuropsychiatric Patient
• Many antiepileptics and antipsychotics produce
weight gain.
• Two agents are associated with weight loss,
topiramate and zonisamide.
• These agents are not approved for weight loss and
are associated with substantial tolerability and
toxicity issues that make them unacceptable for
weight management in primary care.
• When medicating for neuropsychiatric disorders, a
favorable weigh profile should be taken into account
in choosing a medication.
Weight Loss with Topiramate
0
-1
Weight Loss (%)
-2
-3
-4
-5
Placebo
64 mg/d
96 mg/d
192 mg/d
384 mg/d
-6
-7
-8
-9
-10
0
2
4
6
8
10
12
14
16
Weeks of Treatment
Bray et al Obes Res 2003 in press.
18
20
22
24
Zonisamide versus Placebo
0
Placebo
Weight loss (kg)
-2
Zonisamide
-4
-6
-8
0
Gadde IJO 2002 (Abs).
2
4
6
8
10
Week
12
14
16
18
Medications Noted in ACP 2005
Pharmacotherapy Guidelines
Data
Source
Weight Loss
Period for
Weight
Change
Mean
Weight
Change
95% CI
Sibutramine
29 RCTs
52 weeks
4.45 kg
(5.29 - 3.62 kg)
Orlistat
22 RCTs
52 weeks
2.75 kg
(3.31 - 2.20 kg)
Phentermine
9 RCTs
2 - 24 weeks
3.6 kg
(6.0 - 0.6 kg)
Diethylpropion
13 RCTs
6 -52 weeks
3.0 kg
(11.5 - 1.6 kg)
Bupropion
3 RCTs
24 - 52 weeks
2.77 kg
(4.5 - 1.0 kg)
--
Range -14.5 to
+0.4 kg
Fluoxetine
9 RCTs
52 weeks
Annals Internal Medicine 2005;142:523-546.
Obesity Pharmacotherapy Outline
• How to apply drug trial data to clinical practice
• Principles of obesity medication use in clinical practice
• Medications approved for long-term use
–
–
sibutramine (Meridia)
orlistat (Xenical)
• Medications approved for short term use
–
–
phentermine
others rarely used: mazindol, diethylpropion
• Medications for use in special patients
–
–
–
the depressed obese patient – bupropion (Wellbutrin) and
venlafaxine (Effexor)
type 2 diabetes – metformin , pramlintide (Symlin), exendin-4
(Exenatide)
patients with neuropsychiatric problems - topiramate (Topamax)
and zonisamide (Zonegran)
• Medications in development
Van Gaal et al. Lancet 2005;365:1389-97.
Rimonabant Weight Loss and
Waist Change over 1 year
• Mean weight loss 4.8
kg greater than placebo
• Improvements in HDL,
TG, Insulin and HOMAIR greater than with
weight loss alone
• Side effect profile
favorable
Van Gaal et al. Lancet 2005;365:1389-97.
Obesity Pharmacotherapy: What
Does the Future Hold?
• Epidemic of obesity and comorbidities is unabated.
• Understanding of biology underlying obesity continues to
expand.
• New drugs are coming on market – rimonabant 2006.
• Look AHEAD, SOS are evaluating mortality benefit of
weight loss.
• Obesity pharmacotherapy is gaining legitimacy.
Obesity Pharmacotherapy: What
Does the Future Hold?
• Medicating for obesity will follow the paradigm
of other chronic diseases (HTN, DM).
• Medications for obesity will not cure obesity.
• Weight loss of 5-10% will be seen with new
medications.
• Lifestyle will remain a cornerstone of
medicating.