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• The influence of sulfonylurea drugs in enhancing the effect of endogenous insulin is well documented. Furthermore, combination therapy with sulfonylurea and insulin is effective in the treatment of type II diabetes mellitus. Therefore, to assess the efficacy of this type of combination therapy in type I diabetes, we conducted a double-blind clinical trial with tolazamide and insulin in 15 subjects with type I diabetes. The diagnosis of type I diabetes was confirmed by previous episodes of diabetic ketoacidosis and undetectable C-peptide levels in serum samples from blood drawn from patients two hours after breakfast. During the study protocol, placebo or tolazamide was randomly added to insulin and the combination therapy was continued for three months. In the placebo group, levels of fasting plasma glucose (FPG) and hemoglobin A 1c (HbA 1c ) did not alter significantly at the end of the study period. However, in the tolazamide group, levels of FPG and HbA 1c markedly improved after administration of tolazamide (FPG levels before therapy, 10.8±0.9 mmol/L [mean±SEM]; after therapy, 6.7±0.4 mmol/L; HbA 1c levels before therapy, 10.9%±0.6%; after therapy, 9.6%±0.5%). Therefore, adjuvant therapy with tolazamide and insulin may be beneficial in achieving adequate metabolic control in type I diabetes mellitus. ( Arch Intern Med 1988;148:1745-1749)

To the Editor.— Since the recent ban on the use of phenformin hydrochloride by the Food and Drug Administration, we have observed two major adverse drug reactions in patients being switched to tolazamide (Tolinase). Report of Cases.— Case1.—An 83-year-old man was previously treated with phenformin hydrochloride (DBI-TD), 50 mg orally three times a day for four years. Four days after changing to tolazamide, 250 mg orally three times a day, he came to the emergency room of the Medical Center Hospital of Vermont with a history of profuse diaphoresis, confusion, slurred speech, and severe shaking (possibly grand mal seizure, although verification is lacking). While being transported to the emergency room, rescue squad attendants gave the patient a glucose solution to drink. On arrival, the patient was oriented with irregular pulse of 88 beats per minute and blood pressure of 250/120 mm Hg. Monitoring by ECG showed frequent premature ventricular

To the Editor.— The appearance of asymptomatic, bilateral parotid enlargement is widely recognized as a relatively frequent clinical occurrence. It has been noted in Mikulicz syndrome associated with sarcoidosis, in Reiter syndrome, and in several other disorders. However, it is not generally appreciated that this interesting physical finding can also be associated with diabetes mellitus. Report of a Case.— A 50-year-old woman's condition was first diagnosed as adult-onset diabetes mellitus at age 46. After evaluation at another hospital, she was placed on an American Diabetes Association diet and a daily dose of approximately 100 mg of tolbutamide. During the succeeding four years, the patient demonstrated poor diabetic control on numerous occasions and was eventually switched to tolazamide, 500 mg daily. On the day of admission to our hospital, the patient was complaining of dizziness, weakness, and faintness. She gave a history of diabetes, and a blood glucose level determined at

John Garvie, MD, Junior Assistant Resident, Jewish Hospital of St Louis, Department of Medicine: A 46-year-old man with a two-year history of diabetes mellitus controlled with tolazamide treatment and hypertension that responded to methyldopa therapy was admitted for evaluation of episodic palpitations, weakness, and syncope. Two days prior to admission, after eating a large breakfast and taking 100 mg of tolazamide, the patient fainted for a few seconds; he recovered but he felt weak for the remainder of the day. He also related a one-year history of recurrent short-lived episodes of palpitations, chest fullness, headaches, tinnitus, dizziness, nausea, dyspnea, and diaphoresis. There was no history of seizures, documented hypoglycemia, or ketoacidosis. Outpatient plasma glucose levels ranged between 170 and 210 mg/ 100 ml. Medication for the month prior to admission consisted of 250 mg of methyldopa twice a day, 50 mg of imipramine hydrochloride at bedtime, and 100 mg of

• Using a double-blind crossover design, we studied the effect of tolazamide, an orally administered sulfonylurea, in 11 patients with non—insulin-dependent diabetes mellitus, poorly controlled on 40 units/day or more of insulin; all had previously failed to respond adequately to oral hypoglycemic agents and diet. In addition, six nondiabetic sex-, age-, and weightmatched controls were studied. Tolazamide significantly lowered fasting plasma glucose level from 272 ±21 to 222±31 mg/dL, increased fasting C peptide concentration from 0.09 ±0.03 to 0.28±0.10 pmole/mL (controls, 0.23±0.2 pmole/mL), and increased integrated C peptide concentration during a test meal (area under the curve) from 42 ±18 to 95 ± 22 pmole/mL x min (controls, 94 ± 8 pmole/mL x min). These data show that addition of tolazamide markedly increased fasting and meal-stimulated insulin secretion and modestly lowered fasting plasma glucose concentrations. We conclude that some patients who cannot achieve satisfactory control with oral hypoglycemic agents and diet may benefit from combined therapy with oral sulfonylurea agents plus insulin. ( Arch Intern Med 1986;146:673-676)