For those of you who missed the first obesity therapeutics talk on day 1
of ENDO2013, you certainly missed a great review on the past, present, and exciting
future of obesity treatment. It was wonderful to hear about the history of
where obesity treatment has come from. It started with the first sympathomimetic medications and
progressed to present day treatments. Because obesity was first thought of as a
problem of will power and less as an organic disease, most of the treatments
were only designed for a short-term duration. Today, we certainly know much
more about obesity. It is much more than a short-term problem and a problem of
will power! Despite knowing so much more about the molecular pathophysiology,
there are not a lot of therapeutic options for the pharmacologic
treatment of obesity. This is in contrast to type 2 diabetes, for which there
are a multitude of choices. Interestingly, it was pointed out that safety is an
even more significant factor for the dearth of obesity drugs because of
the large numbers of patients that suffer from obesity. Three
relatively new medications were discussed in some detail.
1.)
Lorcaserin (Belviq) - A serotonin 2C receptor agonist which was developed
out of the failure of Fen-phen. Thus far it has shown impressive results with 2
published, randomized, placebo controlled trials (BLOOM trial N Engl J Med
2010;363:245-56./Blossom trial J Clin Endocrinol Metab, October 2011,
96(10):3067–3077.)
2.) Phentermine/topiramate (Qsymia) - The combination of phenteramine (sympathomimetic)
and topiramate (anti-seizure and migraine medication) that has shown >10%
weight loss in 2 randomized studies. One does have to keep in mind birth defect and tachycardia risks.
3.) Bupropion/naltrexone (Contrave) - The mixture of bupropion, a dopamine/norepinephrine reuptake inhibitor used for depression and smoking
cessation, and naltrexone, an opiate antagonist, has also shown great promise
as a weight loss medication. It is currently in phase 3 trials. Hypertension is
a known side effect with bupropion and the FDA has required a study of
cardiovascular safety outcomes prior to approval because of prior concerns for an increase in cardiovascular mortality.
As already described, there is not much else out there, except
maybe metformin, which has limited results and its own side
effects. Pharmaceutical companies are logically very interested in
developing drugs because of the huge potential population and a
few examples were discussed. There seems to be a lot
of excitement around a GLP-1/glucagon mixed agonist and will hopefully
see them on the shelves in the near future.
In closing, as a pediatric endocrinologist, I have even less tools
in the treatment toolbox compared to adult providers. None of the new
treatments are currently available for children and the statistics for children
are no better than for adults. In fact, approximately 1 in 3 children in the US are
overweight or obese and there is data that the damage in terms of
cardiovascular risk is done far earlier than we first thought. As a result,
I eagerly await the results of trials on younger patients so that we can do more than diet and exercise counseling for treatment
for pediatric obesity.
Updates from pediatric endocrinology to come...
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