Introduction
Glyxambi is a fixed-dose combination medication containing empagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) and linagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor). This dual-mechanism oral antidiabetic agent is designed to provide complementary mechanisms for improving glycemic control in adults with type 2 diabetes mellitus.
Mechanism of Action
Glyxambi exerts its glucose-lowering effects through two distinct mechanisms:
Empagliflozin component: Selectively inhibits SGLT2 in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. Linagliptin component: Inhibits DPP-4 enzyme, increasing concentrations of active incretin hormones (GLP-1 and GIP), which stimulates glucose-dependent insulin release and decreases glucagon secretion.Indications
Glyxambi is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both empagliflozin and linagliptin is appropriate.
Dosage and Administration
Standard dosing: 10 mg empagliflozin/5 mg linagliptin once daily in the morning, with or without food Dosage adjustments:- Renal impairment: Not recommended in patients with eGFR <45 mL/min/1.73 m²
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment required based on age alone
- Take whole tablet with water
- Missed dose: Take as soon as remembered unless almost time for next dose
Pharmacokinetics
Absorption:- Empagliflozin: Tmax 1.5 hours; bioavailability ~78%
- Linagliptin: Tmax 1.5 hours; bioavailability ~30%
- Empagliflozin: Protein binding ~86%; Vd ~73.8 L
- Linagliptin: Protein binding ~75-99%; extensive tissue distribution
- Empagliflozin: UGT1A3, UGT1A8, UGT1A9, UGT2B7
- Linagliptin: Minimal metabolism, primarily unchanged
- Empagliflozin: Half-life ~12.4 hours; 41% renal, 54% fecal
- Linagliptin: Half-life ~12 hours; 80% enterohepatic, 5% renal
Contraindications
- History of serious hypersensitivity reaction to empagliflozin, linagliptin, or any component
- Severe renal impairment (eGFR <30 mL/min/1.73 m²)
- End-stage renal disease
- Dialysis patients
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
Warnings and Precautions
Pancreatitis: Monitor for signs and symptoms; discontinue if pancreatitis suspected Heart failure: Monitor for signs and symptoms; consider benefits vs risks Hypersensitivity reactions: Angioedema, urticaria, and bronchial hyperreactivity reported Hypotension: Monitor in elderly, renal impairment, or on diuretics Ketoacidosis: Reports of euglycemic diabetic ketoacidosis; assess risk factors Acute kidney injury: Monitor renal function, especially during initiation Genital mycotic infections: Higher incidence; monitor and treat appropriately Lower limb amputations: Increased risk observed with SGLT2 inhibitorsDrug Interactions
Strong inducers of CYP3A4 or P-gp: May reduce linagliptin concentrations Insulin/insulin secretagogues: Increased risk of hypoglycemia; may require dose reduction Diuretics: Increased risk of volume depletion Other DPP-4 inhibitors: Avoid concomitant useAdverse Effects
Common (≥5%):- Nasopharyngitis
- Urinary tract infections
- Upper respiratory tract infections
- Increased urination
- Pancreatitis
- Hypersensitivity reactions
- Ketoacidosis
- Acute kidney injury
- Severe urinary tract infections
- Fournier's gangrene
Monitoring Parameters
- HbA1c (every 3-6 months)
- Renal function (baseline and periodically)
- Volume status and blood pressure
- Signs/symptoms of hypoglycemia
- Genital hygiene and signs of infection
- Lower limb examinations
- Pancreatitis symptoms
- Liver function tests
Patient Education
- Take medication as prescribed, typically once daily
- Maintain recommended diet and exercise regimen
- Recognize symptoms of hypoglycemia (shaking, sweating, confusion)
- Report symptoms of urinary tract or genital infections
- Monitor for signs of pancreatitis (severe abdominal pain)
- Stay hydrated, especially during illness
- Regular foot examinations recommended
- Inform all healthcare providers about all medications
- Pregnancy planning: Discuss with healthcare provider before conception
References
1. FDA Prescribing Information: Glyxambi (empagliflozin and linagliptin) tablets 2. DeFronzo RA, et al. Diabetes Care. 2015;38(3):384-393 3. Lewin A, et al. J Clin Endocrinol Metab. 2015;100(3):1133-1142 4. American Diabetes Association. Standards of Medical Care in Diabetes—2023 5. Zinman B, et al. N Engl J Med. 2015;373(22):2117-2128 6. Rosenstock J, et al. Lancet Diabetes Endocrinol. 2015;3(5):367-376
This information is provided for educational purposes only and does not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.