Glipizide and Metformin Hydrochloride (Page 4 of 10)

Patients with Inadequate Glycemic Control on Sulfonylurea Monotherapy

In an 18-week, double-blind, active-controlled U.S. clinical trial, a total of 247 patients with type 2 diabetes not adequately controlled (HbA1c ≥ 7.5% and ≤ 12%, and FPG < 300 mg/dL) while being treated with at least one-half the maximum labeled dose of a sulfonylurea (e.g., glyburide 10 mg, glipizide 20 mg) were randomized to receive glipizide (fixed dose, 30 mg), metformin (500 mg), or glipizide and metformin hydrochloride tablets, 5 mg/500 mg. The doses of metformin and glipizide and metformin hydrochloride tablets were titrated (up to the 8 week visit) to a maximum of 4 tablets daily as needed to achieve MDG ≤ 130 mg/dL. Trial data at 18 weeks are summarized in Table 3.

Table 3: Glipizide and Metformin Hydrochloride Tablets in Patients With Inadequate Glycemic Control on Sulfonylurea Alone: Summary of Trial Data at 18 Weeks
*
p < 0.001

Glipizide

5 mg

Tablets

Metformin

500 mg Tablets

Glipizide and Metformin Hydrochloride Tablets,

5 mg/500 mg

Mean Final Dose

30.0 mg

1927 mg

17.5 mg/1747 mg

Hemoglobin A 1c (%)

N = 79

N = 71

N = 80

Baseline Mean

8.87

8.61

8.66

Final Adjusted Mean

8.45

8.36

7.39

Difference from Glipizide

-1.06*

Difference from Metformin

-0.98*

% Patients with Final HbA1c < 7%

8.9%

9.9%

36.3%

Fasting Plasma Glucose (mg/dL)

N = 82

N = 75

N = 81

Baseline Mean

203.6

191.3

194.3

Adjusted Mean Change from Baseline

7.0

6.7

-30.4

Difference from Glipizide

-37.4

Difference from Metformin

-37.2

After 18 weeks, treatment with glipizide and metformin hydrochloride tablets at doses up to 20 mg/2000 mg per day resulted in significantly lower mean final HbA1c and significantly greater mean reductions in FPG compared to glipizide and metformin therapy. Treatment with glipizide and metformin hydrochloride tablets lowered the 3 hour postprandial glucose AUC, compared to baseline, to a significantly greater extent than did the glipizide and the metformin therapies. Glipizide and metformin hydrochloride 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 hydrochloride tablet therapy and either metformin therapy or glipizide therapy. The adjusted mean changes from baseline in body weight were: glipizide and metformin hydrochloride 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 hydrochloride tablets.

INDICATIONS AND USAGE

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:

  1. Severe renal impairment (eGFR below 30 mL/min/1.73 m2) (see WARNINGS and PRECAUTIONS).
  2. Known hypersensitivity to glipizide or metformin hydrochloride.
  3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

WARNINGS

WARNING: LACTIC ACIDOSIS

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL [see PRECAUTIONS].

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see PRECAUTIONS].

If metformin-associated lactic acidosis is suspected, immediately discontinue glipizide and metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see PRECAUTIONS].

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