Introduction
Jentadueto (linagliptin/empagliflozin) is a fixed-dose combination oral antidiabetic medication containing two complementary mechanisms: linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor. This combination therapy is designed to provide dual mechanisms for glycemic control in adults with type 2 diabetes mellitus when both components are appropriate.
Mechanism of Action
Jentadueto exerts its glucose-lowering effects through two distinct mechanisms:
Linagliptin component: Selectively inhibits dipeptidyl peptidase-4 (DPP-4), an enzyme that rapidly degrades incretin hormones. By inhibiting DPP-4, linagliptin increases concentrations of active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in enhanced glucose-dependent insulin secretion and reduced glucagon secretion. Empagliflozin component: Selectively inhibits sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules. This inhibition reduces renal glucose reabsorption, lowers the renal threshold for glucose, and increases urinary glucose excretion.Indications
Jentadueto is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both linagliptin and empagliflozin is appropriate.
Dosage and Administration
Recommended dosage: Available as 2.5 mg linagliptin/5 mg empagliflozin, 2.5 mg linagliptin/10 mg empagliflozin, and 2.5 mg linagliptin/25 mg empagliflozin tablets. Administration: One tablet orally once daily, with or without food. Special populations:- Renal impairment: Not recommended in patients with eGFR <30 mL/min/1.73 m²
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment necessary, but consider age-related renal function decline
- Pregnancy: Category C - use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Both components are rapidly absorbed with median Tmax of 1.5 hours for linagliptin and 1.5-2 hours for empagliflozin. Distribution: Linagliptin is extensively tissue-bound with a large volume of distribution. Empagliflozin is approximately 86% plasma protein bound. Metabolism: Linagliptin undergoes minimal metabolism. Empagliflozin is metabolized primarily via glucuronidation by UGT1A3, UGT1A8, UGT1A9, and UGT2B7. Elimination: Linagliptin is primarily eliminated via the enterohepatic system (80%) and urine (5%). Empagliflozin is eliminated via urine (41%) and feces (54%). Half-lives are approximately 12 hours for empagliflozin and >100 hours for linagliptin.Contraindications
- History of serious hypersensitivity reaction to linagliptin, empagliflozin, or any product components
- Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or patients on dialysis
- Patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis
Warnings and Precautions
Ketoacidosis: Reports of ketoacidosis have occurred in patients with type 2 diabetes. Assess risk factors and monitor appropriately. Acute Kidney Injury: Empagliflozin component may cause acute kidney injury. Monitor renal function periodically. Urosepsis and Pyelonephritis: Serious urinary tract infections have been reported. Hypotension: Empagliflozin causes intravascular volume contraction; symptomatic hypotension may occur. Hypersensitivity Reactions: Serious reactions such as anaphylaxis, angioedema, and exfoliative skin conditions have been reported. Hepatic Effects: Postmarketing reports of hepatic dysfunction, including fatal cases, have occurred with DPP-4 inhibitors. Pancreatitis: Acute pancreatitis has been reported with DPP-4 inhibitors. Lower Limb Amputation: Increased risk observed with empagliflozin in clinical trials.Drug Interactions
Diuretics: May enhance the potential for volume depletion Insulin and insulin secretagogues: May increase risk of hypoglycemia Rifampin: Decreases linagliptin exposure; consider alternative therapy Inducers of UGT enzymes: May decrease empagliflozin exposureAdverse Effects
Common adverse reactions (≥5%):- Nasopharyngitis
- Urinary tract infections
- Headache
- Upper respiratory tract infections
- Increased urination
- Ketoacidosis
- Acute kidney injury
- Urosepsis and pyelonephritis
- Hypersensitivity reactions
- Pancreatitis
- Hepatic impairment
- Severe joint pain
Monitoring Parameters
- HbA1c levels (every 3 months until stable, then every 6 months)
- Renal function (baseline and periodically)
- Volume status and blood pressure
- Signs and symptoms of hypoglycemia
- Urinary tract infections and genital mycotic infections
- Signs of ketoacidosis (even with normal blood glucose)
- Liver function tests
- Lower limb examinations
Patient Education
- Take medication once daily with or without food
- Maintain adequate hydration
- Recognize signs of hypoglycemia (sweating, dizziness, confusion)
- Report symptoms of urinary tract infections (painful urination, frequency)
- Monitor for signs of ketoacidosis (nausea, vomiting, abdominal pain, fatigue)
- Regular foot examinations and proper foot care
- Inform all healthcare providers about all medications being taken
- Do not discontinue without consulting healthcare provider
- Continue diet and exercise recommendations
References
1. Jentadueto® (linagliptin/empagliflozin) prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2022. 2. DeFronzo RA, et al. Efficacy and safety of linagliptin in patients with type 2 diabetes mellitus. Int J Clin Pract. 2011;65(12):1280-1289. 3. Zinman B, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. 4. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 5. Gallwitz B. Linagliptin and empagliflozin: their efficacy and safety as combination therapy. Diabetes Metab Syndr Obes. 2019;12:1167-1175. 6. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors may cause serious infections of the genital area. 2018. 7. EMA Pharmacovigilance Risk Assessment Committee (PRAC). Recommendations on signals. 2019.