Those were the instructions for marketing given to Upjohns salespeople. As indicated by the FDA application, Orinase had been demonstrated "not to be effective in severe diabetes, but only in milder cases of the disease. ": 93  Orinase was one of a new class of drugs (including treatments for hypertension and hypercholesterolemia) aimed at providing marginal benefits over existing treatments for patients who had not previously been a target market for pharmaceuticals. As blood sugar testing for diagnosis of diabetes became more widespread, a curious side effect occurred: because blood sugar testing is not absolutely definitive in diagnoses of diabetes, more  people were receiving borderline tests regarding their glycemic status. These borderline persons could be considered as being at risk for diabetes – prediabetic. Prediabetic patients have elevated blood sugar, but normal levels of sugar in their urine (glycosuria). Upjohn saw an opportunity to benefit and definitely market to a yet-greater expansion of the diabetic population, beyond even the "hidden diabetics" revealed by earlier public health campaigns. Upjohn also found a new use for Orinase: as a diagnostic. Orinase Diagnostic was added to the Orinase product line and, by 1962, was being sold as means of detecting prediabetes in that an abnormal response to Orinase following administration of cortisone in a "stress test" could be taken to indicate prediabetes. Orinase thus not only served to detect a previously hidden patient population, but also detected a patient population most likely to be interested in Orinase as a treatment for their newly diagnosed prediabetes.
Tolbutamide is a first-generation potassium channel blocker, sulfonylurea oral hypoglycemic medication. This drug may be used in the management of type 2 diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas. It is not routinely used due to a higher incidence of adverse effects compared to newer, second-generation sulfonylureas, such as Glibenclamide. It generally has a short duration of action due to its rapid metabolism, so is safe for use in older people. It was discovered in 1956. Side effects
Hypoglycemia
Weight gain
Hypersensitivity: cross-allergicity with sulfonamides
Drug interactions (especially first-generation drugs): Increased hypoglycemia with cimetidine, insulin, salicylates, and sulfonamidesSalicylates displace tolbutamide from its binding site on plasma binding proteins which lead to increase in free tolbutamide concentration, thus hypoglycemic shock. History
Orinase was developed by Upjohn Co. at a time when the primary medical treatment for diabetes was insulin injections. Eli Lilly had a lock on the market for insulin production at the time. Orinase, like other treatments for drugs detected by so-called paraclinical signs rather than clinically observable signs or patient-reported symptoms, benefitted from an increased sensitivity and availability of blood glucose testing. Milton Moskowitz (editor in 1961 of Drug and Cosmetic Industry) claimed the introduction of Orinase, "expanded the total market by bringing under medical care diabetics who were formerly not treated." It did this by changing the mindset about diabetes even more than insulin had.