Classes
DEA Class; Rx
Common Brand Names; Trijardy XR
- Antidiabetics, Biguanides;
- Antidiabetics, Dipeptyl Peptidase-IV Inhibitors;
- Antidiabetics, SGLT2 Inhibitors
Description
Empagliflozin: SGLT2 inhibitor; SGLT2 is expressed in the proximal renal tubules and is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion
Linagliptin: DPP-4 inhibitor; increases and prolongs incretin hormone activity, which is inactivated by DPP-4 enzyme; incretins regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and reducing glucagon secretion from pancreatic alpha cells
Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and use; improves glucose tolerance and lowers both basal and postprandial plasma glucose
Indications
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM)
Empagliflozin is also indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease
Individualize starting dose based on the patient’s current regimen
Monitor effectiveness and tolerability, and adjust dosing as appropriate
Contraindications
Severe renal impairment (eGFR <30 mL/min/1.73 m2), ESRD, or dialysis
Metabolic acidosis, including diabetic ketoacidosis
Hypersensitivity to empagliflozin, linagliptin, metformin, or any of the excipients in the product
Adverse Effects
Upper respiratory tract infection (8-10.3%)
Urinary tract infection (9.6-10.2%)
Metformin
- Hypoglycemia (13.7%)
- Diarrhea (12.5%)
Nasopharyngitis (5.8-8.1%)
Diarrhea (2.2-6.6%)
Constipation (5.1-5.8%)
Gastroenteritis (2.9-5.8%)
Headache (5.1%)
Empagliflozin
- Urinary tract infection (7.6-9.3%)
- Increased LDL cholesterol (4.6-6.5%)
- Female genital mycotic infections (5.4-6.4%)
- Dyslipidemia (2.9-3.9%)
- Male genital mycotic infections (1.6-3.1%)
- Increased hematocrit (2.8%)
- Arthralgia (2.3-2.4%)
- Nausea (1.1-2.3%)
- Thirst (1.5-1.7%)
Linagliptin
- Nasopharyngitis (6.1-7%)
- Diarrhea (3-3.3%)
- Increased uric acid (2.7%)
- Cough (1.4-2.1%)
Metformin
- Decreased vitamin B-12 (~7%)
- Nausea (6.7%)
- Diarrhea (>5%)
- Nausea/vomiting (>5%)
- Flatulence (>5%)
- Abdominal discomfort (>5%)
- Indigestion (>5%)
- Asthenia (>5%)
- Headache (>5%)
Hypoglycemia (0.7%)
Acute pancreatitis, including fatal pancreatitis
Ketoacidosis
Urosepsis and pyelonephritis
Necrotizing fasciitis of the perineum (Fournier gangrene)
Hypersensitivity reactions (eg, anaphylaxis, angioedema, exfoliative skin conditions)
Severe and disabling arthralgia
Bullous pemphigoid
Skin reactions (eg, rash, urticaria)
Mouth ulceration, stomatitis
Warnings
Drug combination not indicated for treatment of type 1 diabetes mellitus
Postmarketing cases of metformin-associated lactic acidosis, including fatal cases, were reported (see Black Box Warnings)
Postmarketing cases of serious urinary tract infections, including urosepsis, were reported; evaluate for signs and symptoms and treat appropriately
Serious hypersensitivity reactions, (eg, angioedema) in patients treated with empagliflozin reported postmarketing; discontinue therapy and treat promptly if it occurs per standard of care
There have been reports of acute pancreatitis, including fatal pancreatitis; if pancreatitis suspected, promptly discontinue
Heart failure observed with 2 other DPP-4 inhibitors; consider risks and benefits in patients with known risk factors for heart failure; monitor for signs and symptoms
Empagliflozin causes intravascular volume contraction; symptomatic hypotension may occur after starting therapy; postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis; assess volume status and correct
Necrotizing fasciitis of the perineum (Fournier gangrene) reported in postmarketing surveillance with SGLT2 inhibitors; it is a rare life-threatening necrotizing infection requiring urgent surgical intervention
Hypersensitivity reactions reported with linagliptin; onset of reactions occurred within the first 3 months after initiating linagliptin; exercise caution with history of angioedema to another DPP-4 inhibitor
In controlled clinical trials of metformin, a decrease to subnormal levels of serum vitamin B-12 levels, without clinical manifestations, was observed
Empagliflozin increases the risks of genital mycotic infections; patients with a history of genital mycotic infections were more likely to develop genital mycotic infections; monitor and treat appropriately
Increased LDL cholesterol may occur with empagliflozin; monitor LDL cholesterol and treat per standard of care
Severe and disabling arthralgia in patients taking DPP-4 inhibitors has been reported; consider discontinuing drug if DPP-4 inhibitor is a cause for severe joint pain
Pregnancy and Lactation
Based on animal data showing adverse renal effects from empagliflozin, use is not recommended during the second and third trimesters of pregnancy
Limited data available with Trijardy XR, linagliptin, or empagliflozin in pregnant women are insufficient to determine a drug-associated risk for major birth defects and miscarriage
Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk
There is limited information regarding the presence of Trijardy XR or its components (empagliflozin, linagliptin, or metformin) in human milk, the effects on the breastfed infant, or the effects on milk production
Maximum Dosage
Maximum recommended daily dose of empagliflozin 25 mg/linagliptin 5 mg/metformin 2000 mg
For metformin TDD 1000 mg: Take Trijardy XR 10 mg/5 mg/1000 mg OR 25 mg/5 mg/1000 mg PO as a single tablet once daily
For metformin TDD 2000 mg: Take Trijardy XR 5 mg/2.5 mg/1000 mg OR 12.5 mg/2.5 mg/1000 mg PO as 2 tablets together once daily
Pediatric
<18 years: Safety and efficacy not established
How supplied
empagliflozin/linagliptin/metformin
tablet
- 5mg/2.5mg/1000mg
- 12.5mg/2.5mg/1000mg
- 10mg/5mg/1000mg
- 25mg/5mg/1000mg