1 INDICATIONS AND USAGE Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older 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 and pediatric patients 10 years of age and older with type 2 diabetes mellitus.

6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in 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) ] For Metformin hydrochloride extended-release tablets, the most common adverse reactions (>5%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

(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 Studies 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.

Metformin Hydrochloride Extended-Release Tablets In placebo-controlled trials, in adults with type 2 diabetes mellitus, 781 patients were administered metformin hydrochloride extended-release tablets.

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

Table 1: Adverse Reactions from Clinical Trials of Metformin Hydrochloride Extended-Release Tablets Occurring >5% and More Common than Placebo in Adults with Type 2 Diabetes Mellitus Metformin Hydrochloride Extended- Released Tablets (n=781) Placebo (n=195) Diarrhea 10% 3% Nausea/Vomiting 7% 2% Diarrhea led to discontinuation of metformin hydrochloride extended-release tablets in 0.6% of patients.

Additionally, the following adverse reactions were reported in ≥1% to ≤5% of metformin hydrochloride extended-release tablets patients and were more commonly reported with metformin hydrochloride extended-release tablets than placebo: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of metformin.

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.