The effect of phenformin on “prediabetes”.

Observations are presented on the cortisone glucose tolerance test in 568 relatives of diabetic patients. Twenty-one per cent showed a positive cortisone glucose tolerance curve, including 4.4 per cent who were regarded overtly diabetic from the conventional glucose tolerance curve. A double-blind study was carried out, on the effect of a 6 week course of phenformin on cortisone-induced glucose intolerance in 60 non-diabetic relations of diabetic persons. Following placebo administration, there was a progressive decline in the number of subjects whose cortisone glucose tolerance curve was rendered normal, to 42 per cent 1 year after discontinuing the agent. With phenformin there was a progressive rise to 71 per cent. The phenformin effect was statistically significantly greater than placebo (0.05 > p > 0.02). These subjects were comprised of 2 groups. In subjects designated “prediabetics,” the conventional glucose tolerance curves were entirely normal. In “probable diabetics,” the conventional glucose tolerance curve showed some abnormality, but not sufficient to be regarded as overt diabetes. In the probable diabetes group, 1 year following placebo marked deterioration of cortisone glucose tolerance occurred, while in the phenformin treated there was improvement. The differences were highly statistically significant 0.005 > p > 0.001). Not 1 of 7 phenformin treated persons became overtly diabetic, whereas 3 of 5 placebo treated showed overt diabetes after 1 year. Following 1 year of observation, no change occurred in the mean values of the cortisone glucose tolerance curve in a group of prediabetics. (p > .0.9). One year after placebo administration a slight fall occurred. (0.05 > p > 0.02), but following phenformin a marked and highly significant drop was observed (p < 0.001). Placebo appears to exert a significant but progressively wanning influence on the glucose intolerance of prediabetes, and no effect on probable diabetes. Phenformin results in marked amelioration of the cortisone-induced glucose intolerance of both prediabetes and probable diabetes, and appears to exert a retarding effect on the development of the diabetic syndrome.