Hepatic Impairment: No pharmacokinetic studies of GLUMETZA have been conducted in subjects with hepatic insufficiency.

Geriatrics: 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.

Table 1: Summary Mean (±SD) of Pharmacokinetic Parameters after One Day Dosing  PK Parameter  Glumetza
2x500 mg  Glumetza
1x500 mg BID  Glucophage
1x500 mg BID 
AUC0-36 (ng.hr/mL)  14182 ± 2415  15260 ± 3496  15342 ± 3398 
Cmax (ng/mL)  1301.4 ± 285.7  811.9 ± 173.7  959.1 ± 204.0 
Tmax (hr)  7.5 ± 1.2  7.1 ± 1.2  4.2 ± 1.6 
Table 2: Mean (±SD) Pharmacokinetic Parameters for Glumetza 1000 mg Tablet and Glumetza 2x500 mg Tablets  PK Parameters  Glumetza
1000 mg Tablet  Glumetza
2x500 mg Tablets 
AUC0-t (ng.hr/mL)  11706 ± 2520  12408 ± 2581 
AUC0-∞ (ng.hr/mL)  11907 ± 2521  12599 ± 2616 
Cmax (ng/mL)  1238 ± 271  1116 ± 254 

GLUMETZA has been studied as monotherapy and in combination with a sulfonylurea and insulin.

In a multicenter, randomized, double-blind