Tag Archives: glitazone



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?


    Association of pioglitazone treatment with decreased bone mineral density

In this Danish trial in just 16 weeks, pioglitazone associated with 1 to 1.4% loss of bone density compared to placebo. http://jcem.endojournals.org/cgi/content/abstract/jc.2007-2249v1

Is this surprising considering that this group of drugs has never been shown to have the safe anabolic benefits of metformin?- which reduces fat mass and increases lean mass, and growth in teenagers with polycystic ovary syndrome.

Metformin reduces lipidemia, new diabetes by half and in diabetics almost halves mortality and all major chronic degenerative diseases. By contrast, like sulphonylureas, gliptins, appetite suppressants and other wannabe metformin substitutes the glitazones and statins have never been shown to have global benefit long term on all-cause mortality and all common aging degenerative diseases – let alone the incredible safety of metformin when used sensibly. Nor has insulin when added as last-ditch therapy in resistant type 2 diabetes.

So it is increasingly medical negligence to prescribe anything but metformin to tolerance early on and permanently in the overweight, including in common maturity-onset diabetics and those with common lipidemia and hypertension, if lifestyle, diet and a blend of natural supplements (including appropriate parenteral sex hormone replacement in men and women with such imbalance) that reduce insulin resistance are inadequate.
There are no long term contraindications to metformin adjusted to tolerance with sensible monitoring.


Health headlines from BBC the past week are ironically contradictory,  profits  or  prophets of gloom.

Sugar- including cane sugar and excess fruit sugar- and cooked/processed fat – are perhaps the greatest slow “foodstuff” poisons commercialised and concentrated by “civilization”.
The industrial society and it’s omnipresent (TV- cellphone) media deliberately ruin children’s health by introducing them early to profitable sweeteners, cooked fats, fast food, TV and computer addictions, instead of natural fresh foods, exercise, playing and books. The inevitable tidal wave of obesity and chronic degenerative disease then becomes further wealth- The Disease Industry for whom Only Disease Pays. .

Obesity may thus be partly genetic, but is not inevitable with sensible habits:
A new twin study from UK found that “Becoming overweight as a child is more likely to be the result of genes than lifestyle”. http://news.bbc.co.uk/2/hi/health/7230065.stm.

But as the Child Growth Foundation says: “Even if someone has a gene which predisposes them to obesity, it doesn’t mean they will become obese if they work hard to eat healthily” . The National Centre for Eating Disorders carefully analyses how much can be done by the individual to reduce genetic risk http://www.eating-disorders.org.uk/docs/obesity.doc .

The only safe intense sweeteners are those which are both plant-sourced and which reduce insulin resistance – eg stevia. The artificial sweeteners that have been proven 100% safe are cyclamate-saccharine – but they do not reduce insulin resistance.

The only OBESITY “drug” that has been proven in major trials and long term follow up to reduce all major chronic diseases and premature deaths – by 1/3- and HALVE new diabetes (and thus cholesterol-lipid- problems) when started well before overweight and hypertension are established, is the 80year old plant extract METFORMIN. This is THE ONLY widely available low cost prescription drug that safely produces an average of 8% weight loss sustained for as long as it is taken consistently at tolerated dose.
In Canadian experience, metformin halves all deaths in type 2 diabetics followed up for a decade; and in preventative trials, it approximately halves the incidence of new type 2 diabetes. Metformin is 100% safe provided it is started at low dose eg ~125mg/day- and increased gradually over 2 weeks to the maximum dose that is well tolerated without excessive diarrhoea, nausea, abdominal bloating or pain. This dose averages about 2.5gms a day in westerners, but (due to genetic variation) may be as low as 250mg/day. It should always be stopped briefly with any acute symptoms or acute illness, and resumed at a tolerated lower dose. It must thus always be taken in consultation with a health professional.
It is understandably rarely promoted by the Disease Industry because it is out of patent, too cheap- and it work too well. For this profitable Industry, Only Disease Pays! So only expensive new drugs are heavily promoted.

Due to the destructive combination of stressful indolence- hours spent every day watching TV instead of playing outside/ sport- and stress (cortisol) and fast food stuffed with sugar and fat, even preteen children (never mind adults at all ages) suffer increasingly from overweight and teenage type 2 diabetes, and girls from polycystic ovary- infertility-hairiness problems.

Synthetic patent weight-reducing and anti-diabetic drugs eg sbutramine, orlistat, the glitazones, have major adverse effects, and have none of the global long term advantages of metformin. The only reason for their prescription is the intensive drug industry marketing imperative.

Apart from correcting the causes outlined above, preventing and treating overweight and diabetes can be easily achieved with a permanent safe low cost natural multicombination of supplements like appetite- and insulin-resistance reducing agents eg vitamins, minerals and biologicals eg metformin/galega, 5HTP, and fish oil tailored to individual tolerance. http://www.ajcn.org/cgi/content/full/83/6/S1499?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&title=n-3+fatty+acids+and+the+metabolic+syndrome.&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

Health advisors who argue against this are rarely un-informed, they have usually chosen ( for profit) to promote drug industry new drugs rather than healthy truth. The Disease Industry will never invest in trials to prove the obvious, since the supplements are not patentable ie not profitable. So they pay cynical lobbyists to argue loudly that such evidence-based natural safe supplements must first be proven in vast longterm trials – although such trial proof is not required for new designer drugs by the Regulators eg the FDA, Medicines Control Councils who are funded by the drug industry! And politicians, governments don’t argue because the drug industry is a huge creator of jobs and revenue.

Modern drugs for chronic disease allowed by the FDA to be freely prescribed are withdrawn only when enough people die: The Americans have just had to stop the glitazone arm of the massive ACCORD trial in diabetics after 25% more deaths occurred on Avandia than in controls. http://www.msnbc.msn.com/id/23029191/. But- lo and behold- there is still no announcement yet about the withdrawal of the unnecessary glitazones that have no overall longterm health benefit except for the investors!.

Thursday, 31 January 2008, 10:27 GMT
Obesity drug use rises eight-fold
Obesity levels are increasing
More than 1m prescriptions are made for obesity drugs a year – eight times the number dispensed seven years ago. The majority of these were for two treatments – sibutramine and orlistat.

Friday, 1 February 2008, 00:14 GMT
Gout surge blamed on sweet drinks