The flush also occurs occasionally in those taking tolbutamide, acetohexamide and tolazamide, and it occurs rarely in those taking second generation agents.
There are no reports of SIADH for acetohexamide, tolazamide, glipizide or glyburide (which have mild diuretic effects).
The study subjects were 55 consecutive patients with NIDDM, 50 men and 5 women, who manifested secondary failure to a first-generation sulfonylurea, ie, cholorpropamide or tolazamide, control during the 6 months between January and June 1992 while they were attending the diabetes clinic at the VA Medical Center in Phoenix, Arizona.
Nineteen subjects were receiving chlorpropamide, and 36 subjects were treated with tolazamide before the change to a second-generation agent.
Finally, no significant alterations in these metabolic values were noted even when the glipizide and glyburide groups were further subdivided according to the specific first-generation drug used, ie, chlorpropamide in 19 subjects and tolazamide in 36 subjects.
The overall frequency of side effects for first-generation agents, however, ranges between 3% and 4% for tolbutamide, acetohexamide, and tolazamide, and 9% for chlorpropamide, as compared with a side-effects frequency of 6% to to 7% for both glyburide and glipizide.
Therefore, we believe that substitution with second-generation sulfonylurea agents in NIDDM subjects following onset of secondary failure to first-generation drugs irrespective of the specific compound, eg, tolbutamide, chlorpropamide, or tolazamide, may be a futile, expensive, and time-wasting maneuver, an opinion also voiced in several reports.[12,13,22] Instead, adjunctive therapy with newer drugs belonging to other classes with alternative modes of action, such as metformin and acarbose, or with insulin[28-33] appears to be an appropriate management option in these subjects who manifest secondary failure to sulfonylurea agents.
All subjects were being treated with oral sulfonylurea agents in maximum daily recommended dosages, ie, tolazamide
, 1000 mg (Tolinase, The Upjohn Company, Kalamazoo, Mich); glyburide, 20 mg (DiaBeta, Hoechst-Roussel Pharmaceuticals, Inc, Somerville, NJ); and glipizide, 40 mg (Glucotrol, Roerig Division of Pfizer, Inc, New York, NY).