Monthly Archives: September 2010

BANNING THE PRESCRIPTION OF THE GLITAZONE ANTIDIABETIC DRUGS

 neil.burman@gmail.com

This was a bad month for Actos (Takeda-Rly Lilly)  and Avandia (Glaxo), another good month for metformin.

As indicated in this week’s NEJM, the glitazone  class of drugs sold commercially as Avandia and Actos, has now belatedly  been suspended,  restricted or black boxed  by the European – EU and the  USA- FDA- regulators  (after shocking prevarication pandering to Big Pharma), because of  promoting  heart failure, let alone visual loss- macular oedema, osteoporosis fractures,  fatal hepatitis (troglitazone deaths), and adiposity –weight gain and  cancer.; with consequently and unsurprisingly no significant reduction in all-cause mortality ..

Regulators like our own MCC  must now surely suspend ie ban the current  glitazone drugs in view of the long-accumulating list of their serious adverse effects and related deaths.. There never was or is compelling clinical reason for their prescription any more than there is or was allowing eg  the soon- banned Mandrax, Ponderax, practolol, stilbestrol, cerivastatin or the original glitazone troglitazone Rezulin on the market.

The current glitazones have  been in use scarely a decade; and  are not necessary let alone essential since:

-metformin remains the best drug ever discovered against all major common degenerative diseases including type 2 diabetes and overweight, with zero serious adverse effects in the longest (20year) randomized controlled trial ever conducted,

– with 1/3 reduction in all mortality and major chronic degenerative disease, halving of heart attacks in type 2 diabetics due to metformin’s unique combination in titrated clinical use of antioxidant, anti-lipidemic, vasodilator antihypertensive, anticancer, anti-aging, appetite- and adiposity-controlling, anti-hepatitis, antimicrobial, insulin-sensitizing, pro-fertility and fibrinolytic benefits, protecting all organ systems;

and at least halving of new diabetes in major preventative trials in “prediabetics” on four continents; and provided the dose of metformin is simply started low- at most 250mg/day

– and provided the starter dose is titrated weekly up to comfortable safe tolerance and desired effect- as must naturally be done with all chronic drugs.

In contrast to the glitazones, the latest studies  October 2010 by Evans ea   from Tayside Scotland and by MacDonald ea in the UK as a whole, showed that compared to sulphonylurea and other antidiabetics, metformin alone or combined with sulphonylurea  in +-75year old diabetics with congestive heart failure lowered all-cause mortality by 41% after 1 years and by about 30% longterm – the same outcome as in the UKPDS trial 30year followup.

From France Mouchiroud ea Sept 2010  discuss why global lifespan has risen from about 46 to 65years accross the 20th century, and how metformin (as dietary restriction mimetic) shares with rapamycin and resveratrol the slowing-down of age-related diseases.  And Li ea Sept 2010  show in experimental stroke in rats how chronic prevention with metformin was neuroprotective  via nitric oxide.

A careful population study in USA by Wertz ea Sept 2010  could find no difference in the 4.15% incidence of heart attack, heartfailure or death in  rosglitazone or pioglitazone users aged 18years or older;   and a careful study by Kaiser Permanente  Sept 2010 of all published glitazone trials confirms Pubmed search, that  after ten years of massive marketing  trials and massive unjustified use, there is  still no evidence that  the glitazones reduce all-cause mortality as metformin does, nor statistically reduce the primary usual glitazone trial endpoint of major cardiovascular event or death. 

How can glitazones have such benefits of metformin  when glitazones  are not dietary restriction mimetics but actually increase adipocytes and thus obesity and hence  cancer?  

 Instead of protecting drug companies’ and their lobbyists’  interests,  will the Regulators everywhere, including the “experts” at the  Universities – medical schools-  now act against these  unnecessary, risky,  fattening antidiabetic glitazones to protect patients?

Or will the leading medical schools and governments  continue ruthlessly  to put their massive monetary support from Big Pharma ahead of  truth, evidence and patients’ interests?

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SIMPLE SAFE LOWCOST RISK MEASUREMENT AND CORRECTION: THE SOCIOECONOMIC IMPACT OF OSTEOPOROSIS

  neil.burman@gmail.com

Already just since April 2010, Pubmed (the on-line catalogue of peer-reviewed medical journal papers)  reveals four reviews – from USA, Mexico, Ireland and Cambridge UK-  on the huge socioeconomic impact of neglect  of long-available safe cheap measurement  and prevention of osteoporosis in aging populations. Especially that osteoporosis is underdiagnosed, and hence the need for improved use of diagnosis screening and preventatives.

And another study  from France reviews the deadly potential cutaneous (let alone gastrointestinal and other) risks of bisphosphonate and strontium drugs  prescribed for osteoporosis . Their  risk of serious adverse effects  may be <1:10 000 – but no study has ever been done comparing such $billion raincheck designer drugs with simple balanced lowcost safe combination of the score of natural supplements (some 7 vitamins, about 8 minerals and 5 human biologicals- costing as little as about US$10 a month) that are proven to prevent and heal osteoporosis let alone have major benefit on most major chronic diseases. .

The analogy is so simple- one does not treat :

anything but major pain with opioids or risky non-steroidal drugs  (or a sore throat with antibiotics) when simple safe modest-dose non-addictive analgesics and local therapy suffice; or

overweight,  or type 2 diabetes , or common mild to moderate hypercholesterolemia with any designer drug but metformin until control (with diet, lifestyle, supplements including metformin and appropriate other hormone adjustments)  is no longer good enough; or

 mild to moderate  hypertension requiring drug therapy with anything but perfectly safe lowdose reserpine plus lowdose amilozide – which suffice in almost 90% of mild to moderate cases- when more modern designer drugs (eg betablockers, angiotensin-converting – enzyme inhibitors and even the older methyldopa and calcium channel blockers) and newer drugs  both have infrequent but serious adverse effects, and are   less effective (they do not have the long duration and safety record of reserpine plus amilozide that makes it so effective even with erratic use) .

The socioeconomic model that measures the impact of a therapy only on one disease eg osteoporosis obviously also by intent supports the global profiteering and job-creation interests of Big Pharma and their well-rewarded allies – Government, Regulators, Universities, Research, Corporations and private practice. For these big-money industries, the use of a safe shotgun of unpatented and nonprescription supplements that more than halves the incidence, premature disability and mortality of both fractures AND all the common major aging degenerative diseases is anathema, since it reduces the Aging Diseases Industry from a $trillion goldmine in the aging who still vote, travel and earn, to a $billion expense when it matters far less- in the very old.

Hence Big Pharma is fighting a global war to abolish free choice of foodstuffs and supplements, conspire with governments to dictate what sources of foodstuffs must be eaten, and put all micronutrient supplement under doctors’ prescription! and above all else, suppress comparisons of designer prescription drugs with the gold standard old drugs and highly effective safe combinations of supplements.

This column has regularly published the growing irrefutable proof that high technology appliances and drugs are simply not needed to measure, prevent and treat common fragility fracture risk or any of the associated linked common chronic degenerative aging diseases.

And Guglielmi ea from Italian and Singapore Universities recently published another landmark review  confirming the voluminous evidence,  recent reviews from UK, that quantitative ultrasound QUS scan has replaced Dual Xray DXA bone mass density BMD  scan as the goldstandard fracture risk measurement test in common practice . Portable lowcost and therefore far more widely available QUS avoids the irradiation risk of costly centralized DXA, and the increasing overreading of bone density and hence risk score with aging due to accumulating calcification over the lower spine and hips.

It is of course intuitively and logically obvious that QUS devices that fix the target bone at a standardized site between the QUS heads as with eg the heelbone in eg the Norland CUBA footbox will eliminate most performer technique variation with a manually moved contact as in eg the Sunlight Beammed system.

Southampton University UK has also just published a study showing good correlation between peripheral QUS measurement and direct bone density measurement of excised fractured femoral heads from elderly hip replacement patients. .  .

And a Madrid team has just published a survey showing good correlation in children between 5 and 12 years between QUS measurements  and calcium-vitamin D intake.

CONCLUSION:  Safe and lowcost QUS can and thus should be used for bone risk measurement at all ages and locations – including schools and even the bedside;  in contrast to DXA which must not be used in those who are pregnant or not  at least post reproductive if not post-middle-aged.

Even in    the chronically frail or mentally dependent, periodic QUS screening is as crucial as eg bloodpressure screening since eg hypertensive , elderly, dementing or stroke patients share so many risk factors, and are thus are even more prone to osteoporosis- and incidental osteoporotic fracture easily converts the walking wounded  from needing supervised care to being totally wheelchair- or- bed- dependent.