cs: Limited data from controlled pharmacokinetic studies of metformin hydrochloride in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged and C is increased, compared to healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see CLINICAL PHARMACOLOGY, Pharmacokinetics ). Metformin treatment should not be initiated in patients 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Gender: In the pharmacokinetic studies in healthy volunteers, there were no important differences between male and female subjects with respect to metformin AUC (males = 268, females = 293) and t (males = 229, females = 260). However, C for metformin were somewhat higher in female subjects (Female/Male C Ratio = 1.4). The gender differences for C are unlikely to be clinically important. Similarly, in controlled clinical studies in patients with type 2 diabetes, the antihyperglycemic effect of metformin hydrochloride tablets was comparable in males and females.
Race: There were no definitive conclusions on the differences between the races with respect to the pharmacokinetics of metformin because of the imbalance in the respective sizes of the racial groups. However, the data suggest a trend towards higher metformin C and AUC values for metformin are obtained in Asian subjects when compared to Caucasian, Hispanic and Black subjects. The differences between the Asian and Caucasian groups are unlikely to be clinically important. In controlled clinical studies of metformin hydrochloride in patients with type 2 diabetes, the antihyperglycemic effect was comparable in whites (n = 249), blacks (n = 51) and Hispanics (n = 24).
Pediatrics: No pharmacokinetic data from studies of GLUMETZA in pediatric subjects are available.
CLINICAL STUDIES
GLUMETZA has been studied as monotherapy and in combination with a sulfonylurea and insulin.
In a multicenter, randomized, double-blind, active-controlled, dose-ranging, parallel group study GLUMETZA 1500 mg once a day, GLUMETZA 1500 per day in divided doses (500 mg in the morning and 1000 mg in the evening), and GLUMETZA 2000 mg once a day were compared to immediate release metformin 1500 mg per day in divided doses (500 mg in the morning and 1000 mg in the evening). (See Table 3) Newly diagnosed patients, diet-and-exercise-treated (diet/exercise) patients, patients who received combination therapy consisting of metformin up to 1500 mg/day plus a sulfonylurea at a dose equal to or less than one-half the maximum dose allowed (following a 6-week washout), or patients on monotherapy with an antihyperglycemic agent (following a 6-week washout) were randomized to treatment and began titration from 1000 mg/day up to their assigned treatment dose over 3 weeks. Metformin IR treatment was initiated as 500 mg BID for 1 week followed by 500 mg with breakfast and 1000 mg with dinner for the second week. The 3-week treatment period was followed by an additional 21-week period at the randomized dose. Each of the GLUMETZA regimens were at least as effective as immediate release metformin in all measures of glycemic control. Additionally, once daily dosing was as effective as the commonly prescribed twice daily dosing of the immediate release metformin formulation.
In a
