BUBBLE, BUBBLE, TOil AND TROUBLE!

... The Biguanide Pot is on the Boil Again Gale and Tattersall questioned the use of biguanide therapy in diabetics [see Inpharma No. 60: p7 (30 Ocl J 976)]. These authors agree that-

• 'The incidence of phenformin-associated lactic acidosis isfrightening. · In a South Australian hospital serving SOO,OOO there were 15 cases in 2 years. They estimate the inciden<;e of known cases oflactic acidosis to be 12 per 1000 phenformin treatment years, with a mortality of 62.S % in affected patients.

• It is difficult to screen out patients who might be susceptible, even in biguanide clinics with drug monitoring facilities. • The place of phenformin as a hypoglycaemic agent is questionable . . Its suggested replacement with metformin is soundly

based. In France, with a metformin consumption 3 times that of phenformin, there were 68 cases of phenformin-associated and 4 of met form in-associated lactic acidosis reported to mid-197S. Thus, the relative risk. with metformin is one-fiftieth of that with phenformin. Physiological studies confirm the decreased risk. Finally, they say - 'We also agree that phenformin

should be withdrawn and that metformin should be used if a biguanide is indicated. ' Phillips. PJ. el al.: British Medical Journal I: 234 (22 Jan 1977)

... Yet Another Warning on Phenformin! -This Time from New Zealand A New Zealand Department of Health circular also draws attention to the danger of phenformin causing lactic acidosis. An informal survey of New Zealand hospitals showed 24 cases of lactic acidosis in patients on phenformin, including 7 deaths. It is recommended that phenformin should not be used with impaired renal function, cardiovascular disease, hepatic dysfunction, conditions associated with tissue anoxia, excessive alcohol intake or poor general health. Great caution is needed with diuretics and in patients over 6S. There have been reports suggesting similar problems with other biguanides. New Zealand Medical Journal 85: 2 I (J 2 Jan 1977)

... But let's Not Go Overboard on Metformin Either Comparison of the effects of metformin and phenformin on blood lactate levels after an IV glucose load (2Sg) and on renal NH4 + excretion after oral acid load (ammonium chloride 0.1 g/kg) showed no statistically significant difference between the 2 drugs, although phenformin did have a greater effect. Maturity onset diabetic patients were studied 3 times: while taking their current biguanide. on diet alone, and on the second biguanide. In all but I patient blood lactate after glucose load was higher during biguanide therapy than on diet alone. Phenformin produced a significant reduction (p < 0.02) and metformin a smaller reduction (0.05 < p < O. J) in mean maximal NH4 + excretion.

'We conclude . .. that both drugs could precipitate lactic acidosis. Although this effect is more pronounced with phenformin we suggest that the same caution should be used when prescribing melformin 10 diabetics, particularly in patients with renal, hepatic or cardiac insufficiency. '

Alexander. W.D. and Marples.J.: Lancet I: 191 (22 Jan 1977)

INPHARMA 5th February, 1977 p3