Race

No information is available on race differences in the pharmacokinetics of glipizide. No studies of metformin pharmacokinetic parameters according to race have been performed. In controlled clinical studies of metformin in patients with type 2 diabetes, the antihyperglycemic effect was comparable in whites (n=249), blacks (n=51), and Hispanics (n=24).

Clinical Studies

Patients with Inadequate Glycemic Control on Diet and Exercise Alone

In a 24-week, double-blind, active-controlled, multicenter international clinical trial, patients with type 2 diabetes, whose hyperglycemia was not adequately controlled with diet and exercise alone (hemoglobin A1c [HbA1c] >7.5% and ≤12% and fasting plasma glucose [FPG] <300 mg/dL) were randomized to receive initial therapy with glipizide 5 mg, metformin 500 mg, Glipizide and Metformin HCl Tablets 2.5 mg/250 mg, or Glipizide and Metformin HCl Tablets 2.5 mg/500 mg. After two weeks, the dose was progressively increased (up to the 12-week visit) to a maximum of four tablets daily in divided doses as needed to reach a target mean daily glucose (MDG) of ≤130 mg/dL. Trial data at 24 weeks are summarized in Table 2.

Table 2: Active-Controlled Trial of Glipizide and Metformin HClTablets in Patients with Inadequate Glycemic Control on Diet and Exercise Alone: Summary of Trial Data at 24 Weeks  Glipizide Metformin Glipizide Glipizide and
 5 mg tablets  500 mg tablets and Metformin HCl Metformin HCl
   2.5 mg/250 2.5 mg/500 mg
   mg tablets tablets
a p<0.001 
Mean Final Dose 16.7 mg 1749 mg 7.9 mg/791 mg 7.4 mg/1477 mg
Hemoglobin A1c (%) N=168 N=171 N=166 N=163
Baseline Mean 9.17 9.15 9.06 9.10
Final Mean 7.36 7.67 6.93 6.95
Adjusted Mean Change
from Baseline -1.77 -1.46 -2.15 -2.14
Difference from
Glipizide   -0.38a -0.37a
Difference from
Metformin   -0.70a -0.69a
% Patients with Final
HbA1c <7% 43.5% 35.1% 59.6% 57.1%
Fasting Plasma
Glucose (mg/dL) N=169 N=176 N=170 N=169
Baseline Mean 210.7 207.4 206.8 203.1
Final Mean 162.1 163.8 152.1 148.7
Adjusted Mean Change
from Baseline -46.2 -42.9 -54.2 -56.5
Difference from
Glipizide   -8.0 -10.4
Difference from
Metformin   -11.3 -13.6

After 24 weeks, treatment with Glipizide and Metformin HCl Tablets 2.5 mg/250 mg and 2.5 mg/500 mg resulted in significantly greater reduction in HbA1c compared to glipizide and to metformin therapy. Also, Glipizide and Metformin HCl Tablets 2.5 mg/250 mg therapy resulted in significant reductions in FPG versus metformin therapy. Increases above fasting glucose and insulin levels were determined at baseline and final study visits by measurement of plasma glucose and insulin for three hours following a standard mixed liquid meal. Treatment with Glipizide and Metformin HCl Tablets lowered the three-hour postprandial glucose AUC, compared to baseline, to a significantly greater extent than did the glipizide and the metformin therapies. Compared to baseline, Glipizide and Metformin HCl Tablets enhanced the postprandi