Obesity Drugs 2010, Which Is the Best?

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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Chemically, Qnexa is made of two medications that individually raise minor red flags – phentermine (from the withdrawn “phen-fen” combo) and topiramate, an epilepsy drug with significant side effects.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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Pharmaceutical analyst who loves blogging about health and medical issues. Has written more than 150 articles and a book on attention deficit disorder. Correctly predicted delayed approval of Bydureon, approval of Provenge by FDA, and the non-approval of Acthar on June 11.

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6 COMMENTS

  1. I believe that Contrave has closer numbers to Qnexa than it does to Lorcaserin regarding % of weight loss. Also another interesting point to raise is that Lorcaserin has shown very low chance of abuse potential, a possible plus for them. Phentermine is close to an amphetamine and abuse does happen with it. Also it is interesting to point out that so far only Qnexa has an advisory panel (meeting July 15th) to discuss it. Some have speculated that this is because they only have questions about Qnexa and the others they plan on rejecting… this however is only rumours nothing more. Also All three drugs do meet the FDA requirements to be classified as obesity reducing drugs. Who really knows what will happen.

    • Yes, I’ve heard that same rumor about Qnexa and the advisory panel – it is very interesting! The exact numbers are hard to get because, to be honest, it has been extremely hard to get medical research articles on these medications, but looking at a piece in the New York Times as well as a few other sources, it seems Contrave is somewhat better than Lorcaserin while still being a significant step below Qnexa.

      The FDA is a difficult beast to understand and only time will tell =)

  2. You guys should perform some more due diligence. Qnexa got a panel review so quickly because the FDA has legitimate concerns about the pharmacodynamics and pharmacokinetics of combining phentermine and topiramate, both compounds with adverse side effects. Combining the two only raises more concerns. The fact Contrave and Qnexa need titration periods is itself an alarm bell. Also, there will be questions about drop outs during the titration period and the cause of those censored data. Add that to the drop out rates (and more importantly, dropout rates due to adverse side effects), and the safety and tolerabllity profiles of both Contrave and Qnexa become even more questionable.

    As for efficacy, all 3 drugs meet the FDA guidances, altho Qnexa had the highest efficacy. But at what cost? Amphetamines can also induce weight loss, but that doesn’t mean they will be approved for weight loss. Investors are forgetting the golden rule of medicine: do no harm.

  3. Your analysis is very accurate and insightful. Fen-Phen killed over 400 women in 1997 because of Cardiac Valvulopathy and Primary Pulmonary Hypertension. Fenfluramine was FDA approved in 1996. The FDA, and Dr Coleman do not want a repeat situation. http://www.pubmed.gov/16144896 There are three issues of weight loss drugs, Efficacy, Safety, and Tolerability. It seems that the FDA’s current thinking is to assure Safety. Please read the FDA’s “2007 Guidance to Industry for Weight Loss Drugs”, also written by Dr Coleman. Faith, Hope, and Charity, and the greatest of these is Safety.

  4. What possible interactions could there be by taking Qnexa & Prozac. I need anti-depressant medication but do not take because i have put on 25 kilos within a 6 month period… could combining the medications assist? im happy to be a guinee pig bc without psychotropic medication my life is suffering, but at same time do not want to become some fat #$%^

  5. Wow, it looks like Contrave has passed through the FDA’s grip!

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