Posts Tagged ‘Actos’

What’s Up with the FDA? Part 3

June 9th, 2011

A new study  finds that  pioglitazone (trade name Actos tm), approved  by the FDA for type 2 diabetes and an alternative to rosiglitazone  trade name Avandia tm),  causes significant weight gain- 3.9 kg or 8.6 lbs. a year.Pioglitazone for diabetes prevention in impaired g… [N Engl J Med. 2011] – PubMed result Rosiglitazone, also approved by the FDA for type 2 diabetes, causes weight gain, 2-3 kg in this study. Comparative effectiveness of pioglitazone and rosi… [Curr Diabetes Rev. 2007] – PubMed result  


It’s no secret that in my opinion the FDA is seriously dysfunctional when it comes to obesity. My focus has been on approval, or the lack thereof, of drugs to treat obesity. The above study, however, highlights another serious defect: the FDA routinely approves drugs which cause weight gain.

In addition to pioglitazone and rosiglitazone, insulin, insulin secretagogues, atypical antipsychotic drugs, (clozapine, olanzapine, risperidone and quetipine) antidepressants including amitriptyline, mirtazapine and some serotonin reuptake inhibitors (SSRIs), Mood stabilizers such as lithium and valproic acid. Antiepileptic drugs including valproate, carbamazepine and gabepentin. Drug-induced weight gain. [Timely Top Med Cardiovasc Dis. 2005] – PubMed result. Also, corticosteroids and antineoplastic agents used in the treatment of breast cancer and migraine prophylaxis. Bodyweight change as an adverse effect of drug tre… [Drug Saf. 1996] – PubMed result. Other drugs causing weight gain include beta-blockers for hypertension. Metabolic sequelae of β-blocker therapy: weighing … [Int J Obes (Lond). 2011] – PubMed result

How much weight gain are we talking about? A 2007 review answered that question, at least in part. Researchers took randomized controlled studies of adult participants compared to placebo and had a duration of at least 3 months. 43 studies were identified covering 25,663 subjects. They found evidence of weight gain for all drugs up to 10 kg (22lbs) at 52 weeks. (Many of these drugs are used for chronic conditions and could be used for many years). They also found that the data on body weight are often not recorded in published clinical trials or is reported in insufficient detail. They conclude, “This side-effect (weight gain) has potentially serious consequences, and should be mentioned to patients.”

Obviously, the FDA does not take weight gain as a serious adverse event and disregards all the evidence on the adverse effect of weight gain. How else to explain the casual acceptance of drugs which cause increase weight and their conduct in discarding drugs with cause weight loss? Of course, were the FDA to treat obesity as a serious chronic disease, they would have to look more closely at those drugs which cause weight gain and consider that in their risk/benefit calculus for the approval or continuation of these drugs.


What’s Up with the FDA? Part 1

May 6th, 2011

Faithful readers will recall that I spent two days last July at the FDA Endocrinologic and Metabolic Advisory Committee reviewing rosiglitizone (Trade name Avandia). Avandia, for type 2 diabetes has been interesting to follow not just because so many persons with obesity develop type 2 diabetes but because, due to its review coming amid the same Advisory Committee’s review of four obesity drugs, provided additional insights, especially into how the FDA evaluated safety concerns.

This became all the more interesting when the FDA decided to keep Avandia on the market, albeit with endhanced warning, but had Abbott Laboratories take sibutramine (trade name Meridia) off the market.  The point was made that Avandia had a number of fatal events, in its intended population while Meridia had no fatal events in a population which was specifically excluded on its label. Yet Meridia was spiked and Avandia was not.

Now comes a meta-analysis of Avandia’s class of drugs, called thiazolidinediones, which also includes pioglitazone, (Trade name Actos). The study, covering 16 studies with 810,000 patients found 170 excess myocardial infactions, 649 excess cases of heart failure and 431 excess deaths for every 100,000 patients who receive Avandia rather than Actos. Probably, this will not be enough for the FDA to take any stronger action against Avandia. See Comparative cardiovascular effects of thiazolidine… [BMJ. 2011] – PubMed result