1 INDICATIONS AND USAGE Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Metformin hydrochloride extended-release tablets are biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ( 1 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Lactic Acidosis [see Boxed Warning and Warnings and Precautions (5.1) ] Vitamin B 12 Deficiency [see Warnings and Precautions (5.2) ] Hypoglycemia [see Warnings and Precautions (5.3) ] Adverse reactions occurring >5% in metformin hydrochloride extended-release tablets clinical trials: hypoglycemia, diarrhea, and nausea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Granules Pharmaceuticals Inc at 1-877-770-3183 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials conducted in the U.S., over 1,000 patients with type 2 diabetes mellitus have been treated with metformin hydrochloride extended-release tablets 1,500 to 2,000 mg/day in active-controlled and placebo-controlled studies with the 500 mg dosage form.

In the add-on to sulfonylurea study, patients receiving background glyburide therapy were randomized to receive add-on treatment of either one of three different regimens of metformin hydrochloride extended-release tablets or placebo.

In total, 431 patients received metformin hydrochloride extended-release tablets and glyburide and 144 patients received placebo and glyburide.

Adverse reactions reported in greater than 5% of patients treated with metformin hydrochloride extended-release tablets that were more common in the combined metformin hydrochloride extended-release tablets and glyburide group than in the placebo and glyburide group are shown in Table 1.

In 0.7% of patients treated with metformin hydrochloride extended-release tablets and glyburide, diarrhea was responsible for discontinuation of study medication compared to no patients in the placebo and glyburide group.

Table 1: Adverse Reactions Reported by >5%* of Patients for the Combined Metformin hydrochloride extended-release tablets Groups Versus Placebo Group Adverse Reaction Metformin hydrochloride extended-release tablets + Glyburide (n=431) Placebo + Glyburide (n=144) Hypoglycemia 14% 5% Diarrhea 13% 6% Nausea 7% 4% *Adverse reactions that were more common in the metformin hydrochloride extended-release tablets-treated than in the placebo-treated patients Laboratory Tests Vitamin B 12 Concentrations In clinical trials of 29-week duration with metformin HCl tablets, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients.

6.2 Post marketing Experience The following adverse reactions have been identified during post-approval use of metformin hydrochloride extended-release tablets.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.