Adverse reactions reported in greater than 5% of patients treated with GLUMETZA that were more common in the combined GLUMETZA and glyburide group than in the placebo and glyburide group are shown in Table1.

In 0.7% of patients treated with GLUMETZA and glyburide, diarrhea was responsible for discontinuation of study medication compared to no patients in the placebo and glyburide group.

Table 1: Treatment-Emergent Adverse Reactions Reported By >5%* of Patients for the Combined GLUMETZA Groups Versus Placebo Group Adverse Reaction GLUMETZA+Glyburide
(n= 431) Placebo+Glyburide
(n= 144)
*AR's that were more common in the GLUMETZA-treated than in the placebo-treated patients.
Hypoglycemia 13.7% 4.9%
Diarrhea 12.5% 5.6%
Nausea 6.7% 4.2%

6.2 Laboratory Tests
Vitamin B12 concentrations

Metformin may lower serum vitamin B12 concentrations. Measurement of hematologic parameters on an annual basis is advised in patients on GLUMETZA and any apparent abnormalities should be appropriately investigated and managed. (See WARNINGS AND PRECAUTIONS (5.6))

7. DRUG INTERACTIONS
7.1 Carbonic Anhydrase Inhibitors
Topiramate or other carbonic anhydrase inhibitors (e.g.,zonisamide, acetazolamide or dichlorphenamide) frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs may induce metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase.

7.2 Cationic Drugs
Cationic drugs (e.g.,amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of GLUMETZA and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.

7.3 Drugs Affecting Glycemic Control
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. When such drugs are administered to a patient receiving GLUMETZA, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving GLUMETZA, the patient should be observed closely for hypoglycemia.

8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects: Pregnancy Category B

Metformin was not teratogenic in rats and rabbits at doses up to 600mg/kg/day, which represent 3 and 6times the maximum recommended human daily dose of 2000mg based on body surface area comparison for rats and rabbits, respectively. However, because animal reproduction studies are not always predictive of human response, Metformin HCl should not be used during pregnancy unless clearly needed.

8.2 Labor and Delivery
The safety and effectiveness of GLUME