Medicine cost

Three weight-loss pills are going up for FDA approval this year, 2010 – Qnexa, lorcaserin, and Contrave.  Here we present the state of the field for weight-loss pills and analyze each treatment.

Currently, there are not that many treatments for obesity right now in terms of medication.  The main three that are commonly used now are sibutramine, orlistat and phentermine.

These medications have minimal efficacy, reducing weight by somewhere around 6-10 pounds over a year.  This is not that great performance and takes a long time to do so.

The amphetamines are extremely effective at reducing appetite but are not used for weight loss due to their very high risk of abuse and addiction.

The three main mechanisms of action for an obesity treatment: 1) appetite suppression 2) reduce absorption of nutrients 3) modify metabolism.  No current treatment commonly used works by increasing metabolism.

There are three treatments heading for FDA approval.

Qnexa: This treatment is so effective that it is scary, causing something like 10% placebo adjusted weight loss.  We’re talking about 25 pounds of weight loss over 6 months.  It’s hard to explain but, while there is nothing we’ve found so far that is a serious issue with this medication, it just gives us bad juju.

One analyst argued that Qnexa might be not allowed for use in people who just aren’t that fat as it is so effective it could cause wasting.

Chemically, Qnexa is made of two medications that individually raise minor red flags – phentermine (from the withdrawn “phen-fen” combo) and topiramate, an epilepsy drug with significant side effects.

That said, it seems that the phentermine is safe and possible that its stimulatory effects will lessen the relaxant/depressant effects of topiramate.  While phentermine is related to amphetamines, it does not seem to have similar dopaminergic effects, meaning less risk of dependence.

As if its weight loss effects weren’t enough, Qnexa may also help with sleep apnea and improve certain markers of cardiac health.

The doses in Qnexa of both treatments is low to try to minimize side effects while getting the benefits of synergy.

We have not been able to attain much scientific data on Qnexa or access much of the scientific papers written on it.  If a reader would be able to help us find some, we would be glad to pay $5.

Contrave: This treatment causes somewhere around 3-6% placebo adjusted weight loss.  It is composed of Wellbutrin combined with Naltrexone.  The theory is that the action of Wellbutrin on the important POMC pathway in the brain will reduce appetite and induce weight loss.

Naltrexone is there to reduce tolerance to that effect.

The dose of Wellbutrin used in Contrave is high and, based off our research, likely to cause serious side effects.  Wellbutrin as monotherapy does not have impressive weight loss effects, and the addition of naltrexone doesn’t seem to make it that much better.

Supporting this claim, on certain measures of efficacy, Contrave did not show statistical superiority to Wellbutrin monotherapy.

As if that weren’t bad enough, Orexigen, the company who is developing Contrave, accidentally overstated how effective their drug is.  Not sure how that happened, but when the news was released, its shares dropped 11% – much more than the amount of weight loss it’s likely to induce.

Lorcaserin: This treatment causes somewhere around 3-4% placebo adjusted weight loss.  This is not that effective.  It is a serotonergic drug that works on 5-HTc receptors contained within the brain to promote satiety.

The second we saw this treatment alarms went off in our head.  The phentermine from “phen-fen” is safe, sure, but the fenfluramine isn’t.  And the reason it was dangerous was that it acted on 5-HT receptors in the heart.

But don’t worry – all is well.  Lorcaserin is 100x more potent to the C receptor than the scary B receptor, and studies to date have not shown significant toxicity.

In terms of efficacy, Lorcaserin is not so great.  In one study we looked at, on the highest dose, 10mg twice daily, about 31% of people on it for just 2 and a half months lost more than 5% of their body weight.

The Quick ‘n Easy

Qnexa: works so well there has to be something scary we don’t know about.

Contrave: works decently but its data was overstated.  Not to mention the significant side effects.

Lorcaserin: not so great efficacy, possibly good for low side effects.  Acts on serotonin receptors that are unpleasantly close to those that led to disaster in the past.

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