Sulfonylureas

Glipizide and Metformin Hydrochloride

Approved 31 Jan 2011OralTablet

The FDA lists this product in 18 strengths and forms.

Indications

Glipizide and metformin hydrochloride tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Contraindications

Glipizide and metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mlL/min/1.73 m 2 ) (see WARNINGS and PRECAUTIONS ). Known hypersensitivity to glipizide or metformin hydrochloride. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.

This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to 1 of 4 treatment groups ( Diabetes 19 (Suppl. 2):747-830, 1970).

UGDP reported that patients treated for 5 years to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality.

Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and benefits of glipizide and of alternative modes of therapy. Although only 1 drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.

Adverse reactions

Glipizide and Metformin Hydrochloride Tablets: In a double-blind 24 week clinical trial involving glipizide and metformin hydrochloride tablets as initial therapy, a total of 172 patients received glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, 173 received glipizide and metformin hydrochloride 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 Tablets 5 mg N=170 Metformin Tablets 500 mg N=177 Glipizide and Metformin Hydrochloride Tablets 2.5 mg/250 mg N=172 Glipizide and Metformin Hydrochloride Tablets 2.5 mg/500 mg 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) 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 hydrochloride tablets as second-line therapy, a total of 87 patients received glipizide and metformin hydrochloride 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 hydrochloride tablets were titrated. Adverse Event Number (%) of Patients Glipizide Tablets a 5 mg N=84 Metformin Tablets a 500 mg N=75 Glipizide and Metformin Hydrochloride Tablets a 5 mg/500 mg N=87 Diarrhea 11 (13.1) 13 (17.3) 16 (18.4) Headache 5 (6) 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) Nausea/vomiting 5 (6) 6 (8) 7 (8) Abdominal pain 7 (8.3) 5 (6.7) 5 (5.7) UTI 4 (4.8) 6 (8) 1 (1.1) Hypoglycemia: In a controlled initial therapy trial of glipizide and metformin hydrochloride 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 glipizide, 0 (0%) for metformin, 13 (7.6%) for glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, and 16 (9.3%) for glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg.

Among patients taking either glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg or glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg, 9 (2.6%) patients discontinued glipizide and metformin hydrochloride tablets due to hypoglycemic symptoms and 1 required medical intervention due to hypoglycemia. In a controlled second-line therapy trial of glipizide and metformin hydrochloride tablets, 5 mg/500 mg, the numbers of patients with hypoglycemia documented by symptoms and a fingerstick blood glucose measurement ≤50 mg/dL were 0 (0%) for glipizide, 1 (1.3%) for metformin, and 11 (12.6%) for glipizide and metformin hydrochloride tablets.

One (1.1%) patient discontinued glipizide and metformin hydrochloride tablets therapy due to hypoglycemic symptoms and none required medical intervention due to hypoglycemia (see PRECAUTIONS ). Gastrointestinal Reactions: Among the most common clinical adverse events in the initial therapy trial were diarrhea and nausea/vomiting; the incidences of these events were lower with both glipizide and metformin hydrochloride tablets dosage strengths than with metformin therapy.

There were 4 (1.2%) patients in the initial therapy trial who discontinued glipizide and metformin hydrochloride tablets therapy due to gastrointestinal (GI) adverse events. Gastrointestinal symptoms of diarrhea, nausea/vomiting, and abdominal pain were comparable among glipizide and metformin hydrochloride tablets, glipizide and metformin in the second-line therapy trial. There were 4 (4.6%) patients in the second-line therapy trial who discontinued glipizide and metformin hydrochloride tablets therapy due to GI adverse events.

Glipizide Gastrointestinal Reactions Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in association with glipizide; glipizide and metformin hydrochloride tablets should be discontinued if this occurs.

Glipizide and Metformin Hydrochloride

Indications

Contraindications

Two medicines in one question?

Warnings and precautions

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

At a glance

Guidelines