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  • Title: Glimepiride pharmacokinetics in obese versus non-obese diabetic patients.
    Author: Shukla UA, Chi EM, Lehr KH.
    Journal: Ann Pharmacother; 2004 Jan; 38(1):30-5. PubMed ID: 14742789.
    Abstract:
    BACKGROUND: Type 2 diabetes is a global concern, accounting for the vast majority of cases of diabetes. Type 2 diabetes is associated with insulin deficiency and insulin resistance and, increasingly, with patients who are overweight or obese. Glimepiride is a popular choice of oral antidiabetic agent for patients with Type 2 diabetes since it increases both insulin secretion and insulin sensitivity and, unlike some other oral agents, is associated with weight neutrality or even weight loss. OBJECTIVE: To assess the pharmacokinetic characteristics of glimepiride and its metabolites in normal-weight and morbidly obese patients with type 2 diabetes to determine whether the pharmacokinetics of glimepiride are altered by obesity. METHODS: Normal-weight (n = 14) and morbidly obese (n = 14) men and women (in a 1:1 ratio) with type 2 diabetes received a single oral dose of glimepiride 8 mg following an overnight fast. Serum concentrations of glimepiride and its metabolites, cyclohexyl hydroxymethyl derivative (MI) and carboxyl derivative (MII), and urinary concentrations of these metabolites were measured. RESULTS: There was no significant difference between the 2 patient groups for glimepiride in terms of mean peak concentration (C(max)) (p = 0.0807), time to reach C(max) (t(max)) (p = 0.9916), AUC(0-24) (p = 0.2609), AUC(0- infinity ) (p = 0.1275), or terminal half-life (p = 0.3076). Mean t(max) values and relative total clearances for the 2 groups were also equivalent. Some differences were noted with respect to the pharmacokinetics of metabolites between the groups. In particular, over a 24-hour period, the morbidly obese group excreted statistically significantly greater amounts of MI (p = 0.0430) and MII (p = 0.0051) compared with the normal-weight group. However, none of the differences was considered clinically significant since these metabolites do not have meaningful pharmacologic activity. CONCLUSIONS: Overall, the results presented here indicate that no intrinsic difference is observed in the oral clearance of glimepiride in obese patients compared with non-obese patients. Given that the dosage is titrated to achieve optimal fasting glucose levels, no special dose consideration is required for the use of glimepiride in the treatment of obese patients with type 2 diabetes.
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