Oral Hypoglycaemic Agents: The First Thirty Years

A series of 1,333 patients with non-insulin dependent diabetes (NIDDM) treated with oral hypoglycaemic agents (OHAs) between 1956 and 1988 is described. In addition there were 137 patients with insulin dependent diabetes (IDDM). When last on OHAs 51% of the patients with NIDDM were free from symptoms and satisfactorily controlled; 262 patients are known to have died, 223 have had to be changed to insulin and in 41 patients it has been possible to stop OHAs as no longer being needed, usually owing to better dietary compliance. Over the 32 years, 606 patients have been lost to follow-up; this represents 6.3% per year. The rate of development of secondary failure between the first and 20th year of treatment has been about 5% per year. Patients with NIDDM treated with OHAs have been more likely to develop clinically significant neuropathy and peripheral vascular disease; they also had a higher incidence of coronary artery disease than those treated with insulin. OHAs were used in the treatment of 110 patients with IDDM in the early stages of the disease; 44% achieved satisfactory blood glucose control for at least 12 months and a few patients for as long as 10 years. Of those with IDDM treated with OHAs, 44 were under 30 years of age; 55% had well controlled blood glucose levels for more than 12 months (median 2.8 years). Side effects have not been a real problem; 27 patients reported episodes of mild hypoglycaemia, skin rashes occurred in 1% of patients on sulphonylureas, and gastrointestinal symptoms in about 4% of those on biguanide. Attention is drawn to the occurrence of hyponatraemia in patients treated with chlorpropamide. It is concluded that the OHAs have now an established place in the treatment of NIDDM, the biggest problem being the tendency to continue to use them when, although symptom free, the patient has hyperglycaemia; to reduce the risks of complications these patients should really be changed to insulin.