doses up to 20 mg/2000 mg per day resulted in significantly lower mean final HbA and significantly greater mean reductions in FPG compared to glipizide and to metformin therapy. 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. Glipizide and Metformin HCl Tablets did not significantly affect fasting insulin levels.
There were no clinically meaningful differences in changes from baseline for all lipid parameters between Glipizide and Metformin HCl Tablets therapy and either metformin therapy or glipizide therapy. The adjusted mean changes from baseline in body weight were: Glipizide and Metformin HCl Tablets 5 mg/500 mg, -0.3 kg; glipizide, -0.4 kg; and metformin, -2.7 kg. Weight loss was greater with metformin than with Glipizide and Metformin HCl Tablets.
Table 1: Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single or Multiple Oral Doses of Metformin Subject Groups: C max b( μg/mL) T max c (hrs) Renal
MetforminDose a (Number of Subjects) Clearance (mL/min)
a All doses given fasting except the first 18 doses of the multiple-dose studies
b Peak plasma concentration
c Time to peak plasma concentration
d SD=single dose
e Combined results (average means) of five studies: mean age 32 years (range 23-59 years)
f Kinetic study done following dose 19, given fasting
gElderly subjects, mean age 71 years (range 65-81 years)
h CLcr=creatinine clearance normalized to body surface area of 1.73 m2
Healthy, Nondiabetic Adults:
500 mg SD d (24)
850 mg SD (74) e
850 mg t.i.d. for 19 doses f (9)
1.03 (±0.33)
1.60 (±0.38)
2.01 (±0.42)
2.75 (±0.81)
2.64 (±0.82)
1.79 (±0.94)
600 (±132)
552 (±139)
642 (±173)
Adults with Type 2 Diabetes:
850 mg SD (23)
850 mg t.i.d. for 19 doses f (9)
1.48 (±0.5)
1.90 (±0.62)
3.32 (±1.08)
2.01 (±1.22)
491 (±138)
550 (±160)
Elderly g, Healthy Nondiabetic
Adults:
850 mg SD (12)
2.45 (±0.70)
2.71 (±1.05)
412 (±98)
Renal-impaired Adults: 850 mg SD
Mild (CLcr h 61-90 mL/min) (5)
Moderate (CLcr 31-60mL/min)(4)
Severe (CLcr 10-30 mL/min) (6)
1.86 (±0.52)
4.12 (±1.83)
3.93 (±0.92)
3.20 (±0.45)
3.75 (±0.50)
4.01 (±1.10)
384 (±122)
108 (±57)
130 (±90)
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 A 1c (%) 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 -
