Comparative effects of phenformin, metformin and glibenclamide on metabolic rhythms in maturity-onset diabetics

Abstract

Twelve hour metabolic rhythms have been performed on six maturity-onset diabetic subjects during successive periods of therapy with phenformin, metformin, and glibenclamide. Moderate control of blood glucose concentration was achieved with phenformin and metformin, the lowest concentrations being found with glibenclamide. Mean blood lactate concentration was grossly elevated during phenformin therapy, moderately elevated with metformin and normal during glibenclamide treatment. Similar patterns were found for the lactate/pyruvate ratio, alanine, glycerol and ketone bodies. Serum triglyceride concentrations were significantly higher during phenformin treatment than with the other two regimes. Serum insulin concentration was higher on glibenclamide than with either biguanide. Most of these effects of the biguanides could be accounted for by an inhibitory effect on hepatic gluconeogenesis. It is concluded that the use of biguanides as hypoglycaemic agents in diabetes is associated with the production of multiple metabolic abnormalities.

Blood lactate and pyruvate levels in diabetic patients treated with biguanides with and without sulphonylureas

“…Sulphonylurea therapy did not affect blood lactate thus confirming in patients on long-term therapy the findings of Nattrass and colleagues in short-term studies [10,13]. Sequential studies to show the effect on blood lactate of the addition of sulphonylurea therapy to biguanide-treated patients are not available but our results, by comparison of these groups, suggest that no improvement would occur.…”

“…The increase found was much less than that which occurs in the syndrome of lactic acidosis secondary to biguanide therapy (5-35 mmol/l [5,9] but is similar to that reported in small groups of asymptomatic patients by other workers [10,11]. The range of values in our patients (0.2-4.4 mmol/l) did not overlap with the range of values reported in severe lactic acidosis.…”

Role of metformin in treatment of diabetes mellitus

“…Phenformin is associated with far more cases of lactic acidosis than metformin (14,45,50,51). Metformin, although as effective as phenformin in treating patients with NIDDM, has lesser effects on lactate metabolism (42,53,54).…”

The effects of diabetes mellitus, exercise, and single doses of biguanides upon lactate metabolism in man.

“…Varma et al (1972) found elevated fasting plasma lactate concentrations in diabetics after treatment with phenformin, whereas Jaillard (1974) observed no effect after either phenformin or metformin. Nattrass et al (1977) compared metabolic rhythms in diabetics during treatment with glibenclamide, phenformin or metformin in a cross-over study and found that, although mean fasting lactate did not change, mean concentrations over 24 h (where food was allowed and gentle exercise encouraged) were elevated by both biguanides, especially phenformin, but not by glibenclamide. We cannot rule out the possibility that, had our diabetics been fed prior to receiving phenformin, our findings might have been different.…”