One in 4,000 patients taking phenformin
develops lactic acidosis (J.
Several other more potent biguanides were also developed, including phenformin
and buformin, but these were discontinued in many countries by the late 1970s secondary to the development of lactic acidosis (6, 7).
Metformin and phenformin
block the peripheral antinociception induced by diclofenac and indomethacinon the formalin test.
In a new study, a team of scientists at the Salk Institute for Biological Studies has found that phenformin
, a derivative of the widely-used diabetes drug metformin, decreased the size of lung tumors in mice and increased the animals' survival.
It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin
, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.
One study revealed that biguanides, phenformin
and metformin were associated with embryo death, although metformin was observed to be less toxic than phenformin
in mouse whole embryo culture (8).
According to the number of cases reported, drugs are grouped in classes I to III: Class I (> 20 published reports): didanosine, asparaginase, azathioprine, valproic acid, pentamidine, mercaptopurine, oestrogen, opiates, tetracycline, steroids, trimethoprim, sulfadiazine, furosemide; Class II (> 10 published reports): rifampin, lamivudine, octreotide, carbamazepine, acetaminophen, phenformin
, interferon [alpha]2b, enalapril, hydrochlorthiazide, cisplatin, erythromycin, cyclopenthiazide; Class III (all medications reported to be associated with pancreatitis).
The differential diagnosis of an anion gap metabolic acidosis includes the presence or ingestion of methanol, uremia, diabetic ketoacidosis, phenformin
, paraldehyde, ischemia, isoniazid, iron, lactate, ethylene glycol, ethanol, salicylates, starvation ketosis, or solvents (the traditional MUDPILES mnemonic).
The FDA pulled phenformin
off the shelves in the 1970s because it had toxic side effects.
About the same time, the FDA ordered four California supplement distributors to recall herbal compounds that illegally contained glyburide or phenformin
, prescription drugs that lower blood sugar levels.
In another case, he said there was evidence that a banned drug, Phenformin
, has been put into the supplements.
Wolfe: Raw milk, aspirin and Reye's Syndrome, tampons and toxic shock, Phenformin
and lactic acidosis, Posicor and Duract are all instances where there was clear, unequivocal data at the FDA showing harm, but where the FDA failed to either ban a product or require necessary labeling.