A 24-week, double-blind, placebo-controlled study of immediate release metformin plus insulin versus insulin plus placebo was conducted in patients with type2 diabetes who failed to achieve adequate glycemic control on insulin alone. Patients randomized to receive metformin plus insulin achieved a reduction in HbA1c of 2.10%, compared to a 1.56% reduction in HbA1c achieved by insulin plus placebo. The improvement in glycemic control was achieved at the final study visit with 16% less insulin, 93.0U/day vs.110.6U/day, metformin plus insulin versus insulin plus placebo, respectively, p=0.04. A second double-blind, placebo-controlled study (n=51), with 16weeks of randomized treatment, demonstrated that in patients with type2 diabetes controlled on insulin for 8weeks with an average HbA1c of 7.46 ±0.97%, the addition of metformin maintained similar glycemic control (HbA1c 7.15 ±0.61 versus 6.97 ±0.62 for metformin plus insulin and placebo plus insulin, respectively) with 19% less insulin versus baseline (reduction of 23.68 ±30.22 versus an increase of 0.43 ±25.20units for metformin plus insulin and placebo plus insulin, p<0.01). In addition, this study demonstrated that the combination of metformin plus insulin resulted in reduction in body weight of 3.11 ±4.30lbs, compared to an increase of 1.30 ±6.08lbs for placebo plus insulin, p=0.01.

INDICATIONS AND USAGE
GLUMETZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type2 diabetes mellitus.

CONTRAINDICATIONS
GLUMETZA is contraindicated in patients with:

Renal disease or renal dysfunction (e.g.,as suggested by serum creatinine levels ≥1.5mg/dL [males], ≥1.4mg/dL [females] or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (seeWARNINGS and PRECAUTIONS).
Known hypersensitivity to metformin hydrochloride.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.
GLUMETZA should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. (Seealso PRECAUTIONS)

WARNINGS
Lactic Acidosis:
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with GLUMETZA; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5mmol/L),