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Principles of Pharmacotherapy in the Management of Obesity
Drugs Approved by FDA for Treating Obesity
Effect of Continuous and Intermittent Phentermine Therapy on Body Weight
0
Time (weeks)
8
24
28
Munro JF et al. Brit Med J 1:352, 1968
Weight Loss (lbs)
36
4
12
16
20
32
Alternate Phentermine
and Dummy
Continuous Phentermine
Continuous Dummy
Orlistat Prevents Fat Digestion and Absorption by Binding to Gastrointestinal Lipases
TG=triglyceride; MG=monoglyceride; FA=fatty acid.
Mucosal Cell
Intestinal Lumen
Orlistat
TG
LIPASE
LIPASE
LIPASE
Bile Acids
Micelle
MG
FA
Effect of Orlistat Dose on Fecal Fat Excretion
Zhi et al. Clin Pharmacol Ther 1994;56:82.
Fecal Fat Excretion (% intake)
Orlistat Daily Dose (mg)
0
200
400
600
800
1000
1200
Effect of Long-term Orlistat Therapy on Body Weight
0
Weeks
52
Torgenson et al. Diabetes Care 2004;27:155
Change in Weight (kg)
104
156
208
P<0.001 vs placebo
-4.1 kg
-6.9 kg
Placebo
Orlistat
Meta-analysis of RCTs Evaluating Effect of Orlistat Therapy on Weight Loss at 1-Year
Padwal et al. Int J Obes 2003;27:1437
*All subjects had type 2 diabetes
WMD=weighted mean difference
Favours Treatment
Favours Control
-10
-5
0
10
5
Independent Effect of Orlistat on Plasma LDL-Cholesterol
Weight Loss Category (%initial body weight)
Change in Plasma LDL-Cholesterol Concentration (mmol/L)
Segal et al. FASEB J. 1999;13:A873.
*P < 0.01 vs placebo. Data pooled from 5 trials (N = 1773).
0 - 5
5 – 10
10 – 15
>15
*
*
*
*
Orlistat Inhibits Dietary Cholesterol Absorption
Cholesterol Absorbed (% ingested)
*P<0.05 vs baseline.
Mittendorfer et al. Obes Res 2001;9:599.
Baseline
Orlistat
*
Gastrointestinal Side Effects of Orlistat Therapy
Sjostrom et al. Lancet 1998;352:167.
Values are percentage of subjects.
Case Report of Effect of Orlistat on Blood Cyclosporin A Concentration
Blood Cyclosporin A Concentration (ng/mL)
Le Beller et al. Transplantation 2000;70:1541.
Time (d)
0
100
200
300
400
Orlistat Start
Switch to Neoral
Sibutramine Blocks Neuronal Monoamine (Serotonin, Norepinephrine, Dopamine) Reuptake
X
= Monoamine
S
S
= Sibutramine
Effect of Continuous vs Intermittent Subutramine Therapy on Body Weight
Body Weight Change (kg)
Wirth and Krause. JAMA 2001;286:1331.
Sibutramine dose=15 mg/d.
Time (wk)
0
4
8
12
16
20
24
28
32
36
40
44
48
Placebo
Intermittent sibutramine
Continuous sibutramine
Run-in
period
Weight Loss
Initial Responders to Sibutramine Can Maintain Long-term Weight Loss
James et al. Lancet 2000:356:2119.
Randomization at 6 months in those with >5% weight loss.
Body Weight (lb.)
Month
2
0
6
4
10
8
14
12
18
16
20
22
24
Placebo
Sibutramine 10-20 mg/d
Weight Maintenance
Use of Sibutramine within a Health Maintenance Organization Enhances Weight Loss
0
Weeks
Porter et al. Am J Manag Care 2004;10:369
Weight Change (kg)
26
52
No drug therapy
Sibutramine therapy
Meta-analysis of RCTs Evaluating Effect of Sibutramine Therapy on Weight Loss at 1-Year
Padwal et al. Int J Obes 2003;27:1437
All subjects had hypertension
WMD=weighted mean difference
Adverse Effects of Sibutramine Therapy
Meridia? Package Insert, 2001.
Blood Pressure and Pulse Rate After 1 Year Sibutramine Therapy in Patients with Controlled Hypertension
McMahon et al. Arch Intern Med 2000;160:2185.
*P<0.05 vs placebo.
Additive Effects of Behavior and Diet Therapy with Pharmacotherapy for Obesity
Weight Change (%)
Wadden et al. Arch Intern Med 2001;161:218.
*P<0.05 vs medication alone.
Time (months)
0
2
4
8
12
10
6
Medication alone
Medication and behavior modification
Medication, behavior modification and meal replacements
*
*