Metformin

GLUMETZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. GLUMETZA is a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Metformin is a biguanide that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.

• Starting dose: 500 mg orally once daily with the evening meal. • Increase the dose in increments of 500 mg every 1 to 2 weeks, up to a maximum of 2,000 mg once daily with the evening meal. • Patients receiving metformin hydrochloride (HCl) tablets may be switched to GLUMETZA once daily at the same total daily dose, up to 2,000 mg once daily. • Swallow GLUMETZA tablets whole and never crush, cut or chew. Renal Impairment: • Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR). o Do not use in patients with eGFR below 30 mL/minute/1.73 m 2. o Initiation is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m 2. o Assess risk/benefit of continuing GLUMETZA if eGFR falls below 45 mL/minute/1.73 m 2. o Discontinue if eGFR falls below 30 mL/minute/1.73 m 2.

GLUMETZA is contraindicated in patients with: • Severe renal impairment (eGFR below 30 mL/minute/1.73 m 2 ). • Known hypersensitivity to metformin. • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. • Severe renal impairment: (eGFR below 30 mL/minute/1.73 m 2 ). • Known hypersensitivity to metformin. • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

Boxed 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. • Lactic Acidosis: See boxed warning. • Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Monitor hematological parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required.

Adverse reactions occurring >5% in GLUMETZA clinical trials: hypoglycemia, diarrhea, and nausea.

Table 2 presents clinically significant drug interactions with GLUMETZA. Table 2: Clinically Significant Drug Interactions with GLUMETZA Carbonic Anhydrase Inhibitors Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with GLUMETZA may increase the risk for lactic acidosis. Intervention: Consider more frequent monitoring of these patients. Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F).