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.
In any case, spironolactone has been found to reduce the bioavailability of oral estradiol, which could be due to induction of estradiol metabolism via CYP3A4. Spironolactone has also been found to inhibit UGT2B7. Spironolactone can also have numerous other interactions, most commonly with other cardiac and blood pressure medications, for instance digoxin.Licorice, which has indirect mineralocorticoid activity by inhibiting mineralocorticoid metabolism, has been found to inhibit the antimineralocorticoid effects of spironolactone. Moreover, the addition of licorice to spironolactone has been found to reduce the antimineralocorticoid side effects of spironolactone in women treated with it for hyperandrogenism, and licorice hence may be used to reduce these side effects in women treated with spironolactone as an antiandrogen who are bothered by them. On the opposite end of the spectrum, spironolactone is useful in reversing licorice-induced hypokalemia. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to attenuate the diuresis and natriuresis induced by spironolactone, but, not to affect its antihypertensive effect.Some research has suggested that spironolactone might be able to interfere with the effectiveness of antidepressant treatment. As the medication acts as an antimineralocorticoid, it is thought that it might be able to reduce the effectiveness of certain antidepressants by interfering with normalization of the hypothalamic–pituitary–adrenal axis and by increasing levels of glucocorticoids such as cortisol. However, other research contradicts this hypothesis and has suggested that spironolactone might actually produce antidepressant effects, for instance studies showing antidepressant-like effects of spironolactone in animals.