Pharmacological intervention: the antidiabetic approach.
Impaired glucose tolerance (IGT) progresses to non-insulin-dependent diabetes mellitus (NIDDM) in many but not all IGT subjects. It remains unsettled whether long-term antidiabetic (i.e. antihyperglycaemic) pharmacotherapy delays the development of NIDDM, and whether such treatment influences macrovascular morbidity and mortality. This report summarizes the results from long-term (> 4 years) antihyperglycaemic interventions addressing these issues. In an American study, tolbutamide (0.5 g 2-3 times daily) promoted a 4-year improvement of glucose tolerance in young, non-obese, mildly diabetic asymptomatic subjects who apparently comprised a mixture of IGT and NIDDM. In a Swedish 5-year study on 178 survivors of myocardial infarction, of whom 79 had intravenous IGT, tolbutamide treatment was associated with improved glucose tolerance, reduced triglyceride levels, and improved 18-month survival. A British 5-year study on a subgroup of about 200 middle-aged men from the Whitehall cohort indicated that phenformin (50 mg once daily) did not influence the deterioration of glucose levels. In a 10-year British study, 241 middle-aged men and women were 4-square randomized to control, weight reduction, placebo and tolbutamide (0.5 g twice daily). A non-lasting reduction of arterial disease was recorded in those on tolbutamide. No reduction of NIDDM development was seen. In a Swedish 10-year study on middle-aged men with IGT, follow-up comprised 59 controls, 98 on diet advice with or without placebo, and 23 on tolbutamide (0.5 g three times daily) added to diet advice. A total of 29% developed NIDDM among controls and 13% in the diet group. In contrast, no subject maintaining tolbutamide treatment developed NIDDM. Moreover, the tolbutamide-treated subjects had reduced blood pressure, triglyceride and cholesterol levels, as well as fewer macrovascular complications. Recently, a lower mortality rate at 22 years after the start of tolbutamide treatment has been recorded. To summarize, treatment with insulin-releasing drugs might help to reduce the development of NIDDM and macrovascular disease in IGT subjects. However, further studies are needed to verify or refute this notion.
Department of Community Medicine, Malmö University Hospital, Sweden.
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Melander
D018849:Controlled Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D003927:Diet, Diabetic; D015444:Exercise; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010629:Phenformin / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D014044:Tolbutamide; D010629:Phenformin