Diabetics need insulin injections to live. But what about “prediabetics,” typically older and heavier individuals, who have none of the symptoms and do not feel sick, but who, over the years, become diabetic? Today, we call them type 2 diabetics. To treat or not to treat was the challenge facing diabetes experts in the 1950s. For Upjohn, manufacturer of Orinase, the answer was obvious.
Insulin injections provide the insulin that cannot be manufactured by the diabetic’s pancreas. Orinase, like insulin, lowers increased blood sugar levels, but it is not an oral insulin and does not help all diabetics. It works by stimulating the release of insulin, which the pancreas must first manufacture.
Orinase (tolbutamide), the first member of the sulfonylurea class of oral antidiabetic drugs and chemically related to sulfanilamide, was approved for marketing in the United States in 1957. Type 2 diabetics did not have to suffer the pain of injections, exercise, or strict diets; they only had to take a pill. Doctors were happy because the pills lowered their patients’ blood sugar and supposedly reduced their long-term risks of diabetic complications, including heart disease, strokes, impaired vision, and kidney failure.
The story does not conclude on a happy note. In 1970, a ten-year study comparing the effectiveness of tolbutamide with a placebo unexpectedly found that tolbutamide-treated patients had a 2.5-fold greater risk of dying of heart disease. The results of this University Group Diabetes Program (UGDP) study was embraced by the Food and Drug Administration and the American Medical Association but savaged by the American Diabetes Association, many physicians using Orinase to treat their patients, and the pharmaceutical manufacturer, Upjohn.
Interpretation of the results of the UGDP study has been subject to criticism, and more than four decades later, a clear picture of Orinase’s effect on the heart has yet to emerge. However, since 1984, all sufonylurea antidiabetic drugs must bear the warning of “increased risk of cardiovascular mortality.” Although Orinase is no longer marketed, generic tolbutamide still is.
SEE ALSO Insulin (1921), Sulfanilamide (1936), Placebos (1955), Glucophage (1958), Human Insulin (1982), Avandia (2010).
Type 2 diabetes is becoming increasingly common in young people, probably due to lack of exercise and obesity, the latter resulting in part from excessive consumption of soft drinks. One twelve-ounce can of a popular cola beverage contains forty grams (about 9.4 teaspoons) of sugar!