Obesity,

Cardiac
Health, and
Bupropion/
Naltrexone
THE DREAM AND THE
NIGHTMARE

Obesity
One-third of the US population is obese
One-third of the US population is overweight
Associated with a plethora of medical complications

T2DM
CVD
HTN
Depression
CAD
Stroke
Some cancers

American Journal of Preventive Medicine

Obesity
Obesity-related morbidity leads to increased
hospitalization and greater mortality
Second to smoking as the leading cause of preventable
death
Estimated medical costs of obesity > $100 billion per
annum
Few drugs available due to efficacy and safety concerns
Fen-phen

Lifestyle modification has long been considered a

mainstay of therapy for obesity, but his intervention has
produced only modest weight loss and no reduction in
major adverse cardiovascular events (MACE). (JAMA)

Obesity Pharmacology
Agents that stimulate POMC signaling
However, direct melanocortin agonists associated with
side effects
Monotherapeutic drug approaches have been modest at
best with a therapeutic plateau
Most likely due to negative feedback from -endorphin
Synergy with two drugs?

Two Drugs
Bupropion (BUP)
DA and NE reuptake inhibitor
Used clinically for depression and smoking cessation

Naltrexone (NAL)
Opioid receptor antagonist
Approved as treatment for opioid and alcohol dependency

Both are associated with minimal weight loss

Conclusion
BUP + NAL combination treatment worked in synergy to
reduce food intake
Effect likely due to increased POMC firing rates
Next step?

Conclusions
BUP + NAL coadministration leads to a weight-reducing
anorectic effect
Longer term studies needed to show divergence
between BUP + NAL and BUP + P
Phase 3 clinical trial run, but the FDA deferred approval
due to increases in blood pressure and heart rate

Conclusions
It is not possible to assess noninferiority due to early
trial termination
Cardiovascular safety of this treatment remains
uncertain and will require evaluation in a new
adequately powered outcome trial.

My conclusion
Perhaps temperance would be best.

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