Metformin hydrochloride is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, Glipizide and Metformin HCl Tablets should only be used in patients with normal renal function (see CONTRAINDICATIONS, WARNINGS, and CLINICAL PHARMACOLOGY: Pharmacokinetics). Because aging is associated with reduced renal function, Glipizide and Metformin HCl Tablets should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of Glipizide and Metformin HCl Tablets (see also WARNINGS and DOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS
Glipizide and Metformin HCl Tablets

In a double-blind 24-week clinical trial involving Glipizide and Metformin HCl Tablets as initial therapy, a total of 172 patients received Glipizide and Metformin HCl Tablets 2.5 mg/250 mg, 173 received Glipizide and Metformin HCl Tablets 2.5 mg/500 mg, 170 received glipizide, and 177 received metformin. The most common clinical adverse events in these treatment groups are listed in Table 4.

Table 4: Clinical Adverse Events >5% in any Treatment Group, by Primary Term, in Initial Therapy Study Adverse Event Number (%) of Patients
Glipizide Metformin Glipizide and Glipizide and
5 mg 500 mg Metformin HCl Metformin
tablets tablets 2.5 mg/250 mg HCl
N=170 N=177 tablets 2.5 mg/500 mg
  N=172 tablets
   N=173
Upper respiratory infection 12 (7.1) 15 (8.5) 17 (9.9) 14 (8.1)
Diarrhea 8 (4.7) 15 (8.5) 4 (2.3) 9 (5.2)
Dizziness 9 (5.3) 2 (1.1) 3 (1.7) 9 (5.2)
Hypertension 17 (10.0) 10 (5.6) 5 (2.9) 6 (3.5)
Nausea/vomiting 6 (3.5) 9 (5.1) 1 (0.6) 3 (1.7)

In a double-blind 18-week clinical trial involving Glipizide and Metformin HCl Tablets as second-line therapy, a total of 87 patients received Glipizide and Metformin HCl Tablets, 84 received glipizide, and 75 received metformin. The most common clinical adverse events in this clinical trial are listed in Table 5.

Table 5: Clinical Adverse Events >5% in any Treatment Group, by Primary Term, in Second-Line Therapy Study a The dose of Glipizide was fixed at 30 mg daily; doses of metformin and Glipizide and 
Metformin HCl Tablets were titrated 
Adverse Event Number (%) of Patients
Glipizide Metformin Glipizide and
5 mg 500 mg Metformin HCl
tabletsa tabletsa 5 mg/500 mg
N=84 N=75 tablets a
N=84 N=75 N=87
Diarrhea 11 (13.1) 13 (17.3) 16 (18.4)
Headache 5 (6.0) 4 (5.3) 11 (12.6)
Upper respiratory infection 11 (13.1) 8 (10.7) 9 (10.3)
Musculoskeletal pain 6 (7.1) 5 (6.7) 7 (8.0)
Nausea/vomiting  5 (6.0) 6 (8.0) 7 (8.0)
Abdominal pain 7 (8.3) 5 (6.7) 5 (5.7)
UTI 4 (4.8) 6 (8.0) 1 (1.1)

Hypoglycemia

In a controlled initial therapy trial of Glipizide and Metformin HCl Tablets 2.5 mg/250 mg and 2.5 mg/500 mg the numbers of patients with hypoglycemia documented by symptoms (such as dizziness, shakiness, sweating, and hunger) and a fingerstick blood glucose measurement ≤50 mg/dL were 5 (2.9%) for glipizi