THE HEAVYWEIGHT OLYMPICS: METFORMIN WINS GOLD. RIMONABANT-Acomplia DISQUALIFIES ITSELF.

The latest Rimonabant  reports  from USA and UK confirm that there is no place for it for overweight : Rimonabant  produces the same average weight loss as metformin (about 6kg/yr, 0.5kg/month more than placebo) but no study yet shows  that it has the safe benefits of metformin adjusted to tolerated dose (average 2gm/day in Caucasians): halving of new diabetes rates, halving of all deaths and almost halving major common degenerative diseases of aging.
Contrary to the lying blatant adverts promoting it below (still on the internet)  in this  latest  (SERENADE)  trial, serious diverse events  were up to 10fold  more frequent with rimonabant versus placebo: dropout 19.6 vs 10.7%; discontinuation 9.4 vs 2.1%; adverse psychiatric psychiatric event 5.1 vs 0%;  dizziness (10.9% vs. 2.1%), nausea (8.7% vs. 3.6%), anxiety (5.8% vs. 3.6%), depressed mood (5.8% vs. 0.7%), asthenia 3.6 vs 0.7% and paresthesia (2.9% vs.1.4%).    This contrasts with the 80year old plant extract metformin which – in dose simply adjusted to tolerance- has never been shown in dozens of trial for up to 20 years to have any serious adverse effects.  
 
 So like acarbose, there is no long term evidence that rimonabant is any competition for metformin for either obesity weight loss or type 2 diabetes.
The FDA has for these good reasons  (and no doubt also the fact that it is not a USA- but Italian- developed drug), . declined to licence rimonabant in USA.   In UK ie Europe , where it was not surprisingly  first registered and  – without evidence of longterm safety and benefit as has been so well established for metformin –  is most heavily ie indefensibly used instead of metformin, there have been already 5 associated deaths and 720 adverse reaction reports.  After the endless problems with amphetamines, fenfluramine, glitazones and gliptins, prescribers should be prosecuted for believing implausible advertisements for a new drug instead of staying with the proven metformin. It is firmly established that prescribers and dispensers  (not snakeoil marketeers or bureaucratic regulators) are responsible for their choice and issuing of  appropriate prescription drugs. Thats what doctors and pharmacists undergo arduous training and  onerous registration for.  .
Rimonabant’s  intended mechanism- blockade of cannabinoid receptors- naturally gives it the opposite action to cannabis- ie it causes depression  and dizziness in about 10%;  nausea, anxiety;   and  is  potentially epileptogenic,  and theoretically predisposes to other neurodegenerative diseases as well as hypertension, heart disease, stroke, pain  and cancer.
 Thus rimonabant  perhaps lessens  obesity longterm  , arthritis  and diabetes   (there is as yet no evidence for this) but  shows no prospect of benefit on all-cause morbidity and mortality. 
It’s like statins for mild-moderate hypercholesterolemia, acarbose  for obesity/diabetes, or  kava/black cohosh for menopause symptoms: why prescribe drugs that can cause acute hepatitis or worse when there are safer and more effective longterm preventatives?
 
refs:
“June 4, 2008 ” Acomplia linked to deaths in the U.K.;  While the FDA has been slammed by some drugmakers for its too-conservative approach to drug approval, it may have made the right move with Acomplia. But recent findings by the U.K.’s drug regulator show Sanofi’s weight-loss drug has been linked to five deaths and 720 adverse reactions since the company launched it in Britain two years ago.” http://bcbsma.medscape.com/viewarticle/575640
July 2007 http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON2031809 The European Medicines Agency has recommended that Acomplia (rimonabant), a medicine for the treatment of obesity, must not be used by patients with major depression or those being treated with antidepressants, because of the risk of psychiatric side effects.Questions and answers    How many people have been treated with Acomplia?
Acomplia was granted marketing authorisation in the EU in June 2006.  Currently, rimonabant has been launched in 19 countries, including 13 European countries.  Up to the end of May 2007, it is estimated that about 240,000 patients have been treated with Acomplia worldwide.  Approximately 41,000 patients have been treated with Acomplia in the United Kingdom.
How many people treated with Acomplia might develop psychiatric side effects?
The evidence suggests that one in ten people who take Acomplia may develop psychiatric side effects.  The commonest psychiatric side effects are low mood and depression.  Anxiety, irritability, nervousness and sleep disorders may also occur commonly.  Approximately one patient in every hundred may experience suicidal thoughts.Up to the end of June 2007, the MHRA had received a total of 318 cases, from UK sources, of adverse drug reactions which were suspected to have been caused by Acomplia.  The total number of adverse reactions reported in these cases was 921 because some reports described more than one adverse reaction.  Three hundred and sixty-four (364) psychiatric reactions have been reported.  Amongst these, there have been 48 reports of depression, 16 reports of suicidal thoughts and one report of self-injury.
 
Nonclinical Overview: CNS Toxicity with Rimonabant        CNS Toxicity. Rimonabant blockade of CB1 receptors appears to influence the anti-convulsant tone of ECS; Rimonabant induced http://www.fda.gov/ohrms/dockets/ac/07/slides/2007-4306s1-09-FDA-Bruno.ppt
 
Continuing on the theme of unexpected toxicity landmines, I wanted to take a look at a highly anticipated obesity drug from Sanofi. Rimonabant is a small
pipeline.corante.com/archives/2004/07/20/worries_about_rimonabant.php – 55k –
 

From Wikipedia, the free encyclopedia 19/8/2008

Rimonabant (also known as SR141716, Acomplia,  is an anorectic anti-obesity drug. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite.

Side effects Shortly after market introduction, press reports and independent studies suggest that side effects occur stronger and more commonly than shown by the manufacturer in their clinical studies. Reports of severe depression are frequent. This is deemed to result from the drug being active in the central nervous system, an area of human physiology so complex that the effects of a drug are extremely difficult to predict or anticipate.[5]

Because the drug has the opposite effects of cannabinoid receptor agonists such as tetrahydrocannabinol (THC, one of the substances found in marijuana), which is neuroprotective against excitotoxicity,[6] it can be theorized that Rimonabant promotes the development of neurodegenerative diseases of the central nervous system such as Multiple sclerosis, Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and Huntington’s disease in persons who are susceptible.[7] The reported development of previously clinically silent multiple sclerosis in one patient taking Rimonabant suggests that any patients with an underlying neurological condition should not take Rimonabant, given the neuroprotective role of the endocannabinoid system in many experimental paradigms of neurological disease.

In June 2007[8]  the US FDA  voted not to recommend the drug’s approval because of concerns over suicidality, depression and other related side effects associated with use of the drug.

The risk benefit ratio on the usage of Rimonabant is not yet established. 

 

 

Rimonabant and the FDA    By Richard N. Fogoros, M.D., http://heartdisease.about.com/b/2008/04/02/rimonabant-and-the-fda.htm April 2, 2008

Rimonabant, the long-awaited weight-loss and smoking-cessation drug that is available in most Western countries except the U.S., took another blow this week at the American College of Cardiology Scientific Sessions in Chicago, where the results of the STRADIVARIUS trial were presented. In this trial, obese patients randomized to receive rimonabant lost significantly more weight and more inches from their waists than patients on placebo, and in addition they had significantly improved HDL, triglyceride, and CRP levels. But unfortunately, the volume of their atherosclerotic plaques (the primary endpoint of the study) was not significantly improved over the placebo group. Furthermore, patients on rimonabant had a significantly higher incidence of psychiatric effects, mainly depression and suicidal ideation. This study may prove to be the final nail in the coffin for rimonabant in the U.S. American doctors and patients who have been anxious for the approval of rimonabant, and who may wonder why the FDA would refrain from approving a drug that significantly improves weight loss, smoking cessation, and lipid and inflammation profiles, should read this article on rimonabant and the FDA.

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com

                     

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One response to “THE HEAVYWEIGHT OLYMPICS: METFORMIN WINS GOLD. RIMONABANT-Acomplia DISQUALIFIES ITSELF.

  1. Pingback: INDEX OF RECENT MAIN TOPICS « Healthspanlife – the Official Life! Blog

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