Traditional pharmacological management of non-insulin-dependent diabetes

Most traditional hypoglycemic treatments for non-insulin-dependent diabetes mellitus (NIDDM) are of considerable antiquity. What we would now call a low-carbohydrate diet was first used in 1796; insulin was introduced in 1922; the (toxic) biguanide synthalin was used sparingly from 1926 until the Second World War; and tolbutamide and chlorpropamide were marketed in the late 1950s. Amphetamine was available as an anorectic agent in the 1950s. Hence, representatives of all our present treatments for NIDDM have been available for over 30 y, but there is still great uncertainty about how to use them best. This uncertainty is reflected in major variations in prescription rates from country to country. In spite of this formidable pharmacological armamentarium, we have to face the fact that glycemic control is unsatisfactory in the majority of patients with NIDDM; irrespective of the mode of treatment, less than a quarter have a normal glycated hemoglobin. We clearly need new approaches to control glycemia in NIDDM. Furthermore, in addition to high blood glucose, many patients with NIDDM also have hypertension, hyperlipidemia, and other atherogenic abnormalities that need to be tackled if mortality (predominantly from atherosclerotic vascular disease) is to be reduced. It seems improbable that a single drug will be found to cure the many metabolic abnormalities. Polypharmacy thus seems inevitable for many patients.