Eligible health care professionals may request available samples, vouchers, and/or coupons for SEGLUROMET for use with their appropriate adult patients.

Indication

SEGLUROMET^® (ertugliflozin and metformin HCl) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. SEGLUROMET is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

Selected Safety Information

Contraindications: Hypersensitivity to ertugliflozin, metformin, or any excipient in SEGULORMET, reactions such as angioedema or anaphylaxis have occurred. Patients with severe renal impairment (eGFR [estimated glomerular filtration rate] less than 30 mL/min/1.73 m²), end stage-renal disease (ESRD), or on dialysis. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Lactic Acidosis: There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue SEGLUROMET and promptly notify their health care provider.

For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below:

Renal Impairment: Obtain an eGFR prior to initiating therapy and at least annually in all patients taking SEGLUROMET and more frequently in patients at increased risk of developing renal impairment. In patients with volume depletion, correct before initiating SEGLUROMET. Use of SEGLUROMET is not recommended in patients with an eGFR less than 45 mL/min/1.73 m². SEGLUROMET is contraindicated in patients with severe renal impairment (an eGFR less than 30 mL/min/1.73 m²), end stage-renal disease (ESRD), or on dialysis.

Drug Interactions: More frequent monitoring is recommended when administered with drugs that impair renal function, result in hemodynamic change, interfere with acid-base balance, or increase metformin accumulation.

Age 65 or Greater: Assess renal function more frequently.

Radiological Studies with Contrast: Stop SEGLUROMET at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR of less than 60 mL/min/1.73 m²; in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure and restart SEGLUROMET if renal function is stable.

Surgery and Other Procedures: Discontinue while patients have restricted food and fluid intake.

Hypoxic States: Discontinue in conditions associated with hypoxemia.

Excessive Alcohol Intake: Warn patients against excessive alcohol intake.

Hepatic Impairment: Avoid use in patients with evidence of hepatic disease.

Ketoacidosis: Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been identified in patients with type 1 or type 2 diabetes receiving sodium glucose co-transporter 2 (SGLT2) inhibitors, including ertugliflozin. Some cases were fatal. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. The risk of ketoacidosis may be greater with higher doses. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, discontinue SEGLUROMET, evaluate, treat promptly, and ensure risks for ketoacidosis are resolved prior to restarting. Before initiating, consider risk factors. Consider temporarily discontinuing SEGLUROMET for at least 4 days prior to scheduled surgery. Monitor patients and temporarily discontinue SEGLUROMET in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery). Educate patients on the signs and symptoms of ketoacidosis. Instruct patients to discontinue SEGLUROMET and seek medical attention immediately if signs and symptoms occur.

Lower Limb Amputation: In a long-term cardiovascular outcomes study, in patients with type 2 diabetes and established cardiovascular disease, the occurrence of non-traumatic lower limb amputations was higher with ertugliflozin compared to placebo. Amputation of the toe and foot were most frequent (81 out of 109 patients with lower limb amputations). Some patients had multiple amputations, some involving both lower limbs. Lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation. Patients with amputations were more likely to be male, have higher A1C (%) at baseline, have a history of peripheral arterial disease, amputation or peripheral revascularization procedure, diabetic foot, and have been taking diuretics or insulin. Across seven Phase 3 clinical trials with ertugliflozin, non-traumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the ertugliflozin 5 mg group, and 8 (0.5%) patients in the ertugliflozin 15 mg group. Before initiating SEGLUROMET, consider factors that may predispose patients to the need for amputations. Monitor patients and discontinue SEGLUROMET if complications occur. Counsel patients about the importance of routine preventative foot care.

Volume Depletion: SEGLUROMET can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including SEGLUROMET. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m²), elderly patients, patients with low systolic blood pressure, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating SEGLUROMET in these patients, assess volume status and renal function. Correct volume depletion before initiating SEGLUROMET. Monitor for signs and symptoms of volume depletion and renal function after initiating therapy.

Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate for urinary tract infections and treat promptly.

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. SEGLUROMET may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with SEGLUROMET.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): A rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention has been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including ertugliflozin. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with SEGLUROMET presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue SEGLUROMET, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.

Genital Mycotic Infections: Ertugliflozin increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately.

Vitamin B₁₂ Deficiency: Certain individuals with inadequate vitamin B₁₂ or calcium intake or absorption appear to be predisposed to developing subnormal vitamin B₁₂ levels. Measure hematologic parameters on an annual basis and vitamin B₁₂ at 2 to 3 year intervals in patients on metformin and manage abnormalities.

The most common adverse reactions associated with ertugliflozin (≥5%) were female genital mycotic infections. The most common adverse reactions associated with metformin (≥5%) were diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.

Before prescribing SEGLUROMET, please read the accompanying Prescribing Information, including the Boxed Warning about lactic acidosis. The Medication Guide also is available.