Long-term treatment with the dual antithromboxane agent picotamide decreases microalbuminuria in normotensive type 2 diabetic patients.

Picotamide both inhibits thromboxane synthetase and acts as a thromboxane antagonist at the receptor level. We investigated the long-term effect of picotamide on urinary albumin excretion (UAE) at rest and induced by exercise in 30 type 2 diabetic patients who were normotensive and had microalbuminuria while at rest. The subjects of our study had a mean age of 52.5 +/- 1.6 years, BMI of 28.5 +/- 0.7 kg/m2, diabetes duration of 9.1 +/- 1.8 years, and HbA1c of 7.0 +/- 0.8%. The study was a randomized double-blind placebo-controlled trial. The patients were randomly allocated to receive for 1 year either picotamide, 300 mg, 3 tablets/day, or placebo, 3 tablets/day. The patients were asked to visit our outpatient clinic after 1, 3, 6, 9, and 12 months of treatment. At all times, blood pressure, microalbuminuria at rest, blood glucose, serum creatinine, serum picotamide, and creatinine clearance were measured; at baseline and after 6 and 12 months, all patients underwent submaximal physical exercise. After 6 months of picotamide, baseline and exercise-induced microalbuminuria were significantly decreased (up to one-third) as compared with the baseline and placebo level, with no further drops at month 12 of picotamide treatment. On placebo treatment, UAE at rest and after exercise was slightly increased compared with baseline values. The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control. Our study is the first long-term intervention trial in type 2 diabetes showing that an antithromboxane agent is able to decrease microalbuminuria, which in this disease is a dual marker of macro- and microangiopathy. Our findings suggest an important role for thromboxane in the pathophysiology of microalbuminuria in diabetes; moreover, we hypothesize that antithromboxane agents may have a place in the treatment/prevention of both macro- and microvascular complications in type 2 diabetic patients.

Effect of long-term administration of picotamide on baseline and exercise-induced urinary albumin excretion in patients with type II diabetes mellitus and incipient nephropathy.

The present pilot study investigated the effect of long-term treatment with picotamide on baseline and exercise-induced urinary albumin excretion levels in normotensive patients with type II diabetes mellitus. Six patients with type II diabetes were studied: four patients (two men and two women; mean age, 52 +/- 11 years) were treated for 9 months with picotamide (300 mg, TID) and two patients who did not receive the study medication served as controls. Three of the picotamide-treated patients were given a cycloergometric exercise test at baseline and after 3 and 6 months of therapy to evaluate the effects of the drug on exercise-induced microalbuminuria. Microalbuminuria at rest was measured in all patients at baseline and after 3, 6, and 9 months. At the end of the study, all the picotamide-treated patients demonstrated a significant decrease in microalbuminuria at rest (from 41.7 +/- 12.7 micrograms/min at baseline to 11.8 +/- 3 micrograms/min after 9 months) and after exercise (peak at baseline 103 +/- 36 micrograms/min vs 65.8 +/- 11 micrograms/min after 6 months). Conversely, in the two controls, microalbuminuria at rest increased from 45.1 +/- 0.9 micrograms/min at baseline to 151 +/- 59 micrograms/min at the end of the 9-month study period. (All values given as mean +/- SEM.) In conclusion, long-term administration of picotamide was effective in reducing abnormal exercise-induced microalbuminuria and albuminuria at rest. These findings suggest that long-term treatment with picotamide of normotensive patients with type II diabetes mellitus and incipient nephropathy may slow the progression of the nephropathy in its early stages.