• Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• Empagliflozin is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease.

GLYXAMBI is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

Fatal cases of ketoacidosis have been reported in patients taking empagliflozin. Before initiating GLYXAMBI, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse.

In patients with volume depletion, correct this condition before initiating GLYXAMBI.

For patients who undergo scheduled surgery, consider temporarily discontinuing GLYXAMBI for at least 3 days prior to surgery.

Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests.

Acute pancreatitis, including fatal pancreatitis, has been reported in patients treated with linagliptin. GLYXAMBI has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using GLYXAMBI.

GLYXAMBI is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m². GLYXAMBI is likely to be ineffective in this setting based upon its mechanism of action.

GLYXAMBI may be used in patients with hepatic impairment.

GLYXAMBI is contraindicated in patients with patients on dialysis.

Empagliflozin increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes.

There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including empagliflozin.

Empagliflozin increases the risk for genital mycotic infections.

An association between DPP-4 inhibitor treatment and heart failure has been observed in cardiovascular outcomes trials for two other members of the DPP-4 inhibitor class. Consider the risks and benefits of GLYXAMBI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy.

Empagliflozin causes intravascular volume contraction. Symptomatic hypotension may occur after initiating empagliflozin.

Increases in LDL-C can occur with empagliflozin.

Insulin and insulin secretagogues are known to cause hypoglycemia.

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use.

Reports of necrotizing fasciitis of the perineum (Fournier’s gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including empagliflozin. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death.

Empagliflozin is associated with osmotic diuresis, which could affect hydration status of patients age 75 years and older.

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with linagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with linagliptin, with some reports occurring after the first dose.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years.

Co-administration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

Use of alternative treatments is strongly recommended when linagliptin is to be administered with a strong P-gp or CYP3A4 inducer.

Co-administration of empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia.

Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Therefore, use of alternative treatments is strongly recommended when linagliptin is to be administered with a strong P-gp or CYP3A4 inducer.

Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control.

Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors.

Based on animal data showing adverse renal effects, from empagliflozin, GLYXAMBI is not recommended during the second and third trimesters of pregnancy.

Because of the potential for serious adverse reactions in a breastfed infant, including the potential for empagliflozin to affect postnatal renal development, advise patients that use of GLYXAMBI is not recommended while breastfeeding.

GoToSource

• Use in patients under the age of 18. GoToSource 

• Treatment of type 1 diabetes mellitus or diabetic ketoacidosis. GoToSource 

• Dosage greater than 25 mg empagliflozin/5 mg linagliptin per day in patients with normal renal function. GoToSource

Ketoacidosis (high levels of blood acids/ketones). GoToSource

Severe and disabling joint pain. GoToSource

Life-threatening blood infections (urosepsis), urinary tract infections, kidney infections and kidney failure. GoToSource

Nasopharyngitis, upper respiratory tract infections, pancreatitis (inflammation of pancreas), hypotension (low blood pressure), genital mycotic infections, hypersensitivity reactions and increased LDL-C. GoToSource

Necrotizing fasciitis of the perineum (fournier’s gangrene). GoToSource

Liver injury. GoToSource

Ketoacidosis (high levels of blood acids) and hypoglycemia (low blood sugar). GoToSource

Increased risk of heart failure. GoToSource

Bullous pemphigoid (blistering skin condition). GoToSource

Lawsuits filed for ketoacidosis, kidney failure, heart attacks, strokes, fournier’s gangrene and death.