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SAFETY, EFFICACY, AND PHARMACOKINETICS OF GLIMEPIRIDE IN DIABETIC PATIENTS WITH RENAL IMPAIRMENT OVER A 3-MONTH PERIOD

The safety, efficacy, and pharmacokinetics of glimepiride were investigated in a multiple-dose, open study in subjects with non-insulin dependent diabetes mellitus (NIDDM) and renal impairment. Glimepiride was given to 19 patients over a 3-month period. NIDDM patients were divided into two groups with creatinine clearance of 30-60 and 10-30 mL/min. The initial daily dose of 1 mg glimepiride was adjusted within the range of 1-8 mg to achieve good glucose control. Safety evaluation and tests were performed before, and 1, 2 and 3 months after start of the trial. Standard safety parameters were observed: vital signs, standard clinical biochemistry and hematology determinations, etc. Adverse events were monitored and recorded throughout the study. Glimepiride was well tolerated and there were no drug-related adverse events other than recurrent hypoglycemia episodes in one patient (she did not require further antidiabetic drug treatment thereafter). Three of 19 subjects were not eligible for efficacy and pharmacokinetic evaluation, two of them due to inadequate glycemic control and one due to his decision to withdraw from the study. The therapeutic goal of a fasting blood glucose level of <9.99 mmol/L was reached in 12 out of 16 patients with doses of 1-4 mg glimepiride. Pharmacokinetic evaluation showed an increase in the mean relative total clearance in proportion to the degree of renal impairment, whereas the mean volume of distribution, terminal half life and mean time remained unchanged. The increased plasma elimination of glimepiride with decreasing kidney function could be explained by altered protein binding with an increase in unbound drug. In conclusion, glimepiride is safe, well tolerated and effective in diabetic patients with renal impairment, and the dose can be appropriately titrated on the basis of fasting blood glucose levels.

safety; efficacy; pharmacokinetics; glimepiride; non-insulin dependent diabetes mellitus; renal impairment

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