Adult Dosing
Type 2 diabetes mellitus
For patients currently not treated with metformin
- Initial dose: 2.5 mg/500 mg PO bid
- Max: 2.5 mg/1000 mg bid
For patients already treated with metformin
- Initial dose: 2.5 mg linagliptin and the current metformin dose PO bid; e.g. if treated with metformin 1000 mg bid, start with 2.5 mg/1000 mg PO bid
- Max: 2.5 mg/1000 mg bid
Notes:- Individualize dosage on the basis of both efficacy and tolerability
- Administer dose with meals
- Perform dose escalation gradually to reduce the GI side effects associated with metformin use
- Patients already undergoing therapy with linagliptin and metformin individual components may be switched to linagliptin/metformin combination containing the same doses of each component
- When co-administered with an insulin secretagogue such as a sulfonylurea, a lower dosage of insulin secretagogue may be considered to reduce the risk of hypoglycemia
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
See Supplemental Patient Information
- Accumulation of metformin may cause a rare, but fatal, complication called lactic acidosis. Patients with sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute CHF are at a greater risk for developing lactic acidosis [US Black Box Warning]
- Lactic acidosis may also occur in association with certain pathophysiologic conditions, including diabetes mellitus, and in presence of significant tissue hypoperfusion and hypoxemia
- Lab abnormalities include elevated blood lactate levels (>5 mmol/L), low blood pH, electrolyte disturbances with an increased anion gap, and an elevated lactate/pyruvate ratio [US Black Box Warning]
- Diabetic patients with significant renal impairment, including intrinsic renal disorder and renal hypoperfusion, often in the setting of multiple concurrent medical/surgical problems and multiple concurrent medications are more prone to lactic acidosis
- The risk of lactic acidosis increases with the patient's age and degree of renal impairment. Periodically monitor renal function in patients receiving this combination drug, particularly in geriatric patients. Avoid therapy unless measurement of creatinine clearance demonstrates that renal function is not reduced. Withdraw therapy in the presence of any condition associated with hypoxemia, dehydration, or sepsis
- Avoid therapy in patients with clinical or laboratory evidence of hepatic impairment
- Temporarily discontinue treatment prior to any intravascular radiocontrast study and for any surgical procedure that necessitates restricted intake of food or fluids. Withhold therapy for 48 hours subsequent to the procedure and reinstitute only after renal function is confirmed to be normal
- The risk of metformin-induced lactic acidosis may be exacerbated with topiramate, which is used in epilepsy and migraine prophylaxis
- Lactic acidosis is manifested by nonspecific symptoms including malaise, myalgias, respiratory distress, increasing somnolence, and abdominal distress [US Black Box Warning]
- Severe acidosis may be associated with hypothermia, hypotension, and resistant bradyarrhythmias. Educate patients to recognize and promptly report these symptoms. Discontinue therapy until lactic acidosis is ruled out, if such symptoms occur
- Gastrointestinal symptoms may occur in association with lactic acidosis or other serious disease
- Fasting venous plasma lactate levels above the upper limit of normal but <5 mmol/L in patients receiving therapy do not necessarily signify impending lactic acidosis, and may occur as a result of poorly controlled diabetes /obesity, vigorous physical activity, or technical issues in sample handling
- Suspect lactic acidosis in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis including ketonuria and ketonemia. Discontinue therapy immediately and promptly institute supportive measures in patients with lactic acidosis [US Black Box Warning]
- Postmarketing cases of acute pancreatitis, with fatalities have been reported in patients receiving linagliptin/metformin. Discontinue therapy and initiate appropriate management upon suspicion of pancreatitis
- Renal impairment increases the risk of metformin accumulation, thereby increasing the risk of lactic acidosis. Therapy is therefore contraindicated in patients with renal impairment
- Assess renal function and confirm it to be normal before therapy initiation and regularly thereafter. Continue linagliptin as a single entity tablet at the same total daily dose of 5 mg if this combination drug is discontinued due to evidence of renal impairment
- Exercise caution when using linagliptin/metformin concomitantly with drugs that may affect renal function or result in marked hemodynamic change or may interfere with metformin disposition
- When co-administered with an insulin secretagogue such as a sulfonylurea, a lower dosage of insulin secretagogue may be considered to reduce the risk of hypoglycemia
- Elderly, alcoholic, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency are at a greater risk of hypoglycemia
- Metformin may cause reductions in vitamin B12 levels, which is very rarely associated with anemia; this may be reversed by discontinuation of therapy or vitamin B12 supplementation. Monitor hematologic parameters and vitamin B12 levels regularly during therapy. Appropriately investigate and manage any apparent abnormalities
- Alcohol may augment the effect of metformin on lactate metabolism. Caution patients against excessive intake of alcohol during therapy
- Cardiovascular collapse resulting from acute CHF, acute MI, and other conditions characterized by hypoxemia has been associated with lactic acidosis and may cause prerenal azotemia. Discontinue therapy if any such symptoms occur
- Lack of conclusive evidence exists for macrovascular risk reduction associated with linagliptin or metformin or any other antidiabetic drug
Cautions: Use cautiously in
- Risk of hypoglycemia
- CHF
- Concomitant use with beta-adrenergic blockers
- Co-administration with glucose-lowering agents
- Concomitant use of cationic drugs
Supplemental Patient Information
- Advise patients to remain alert to signs and symptoms of lactic acidosis and promptly notify any unexplained symptoms to their physician
- Educate patients about the importance of adherence to dietary instructions, regular exercise program, regular monitoring of blood glucose, HbA1c, renal function and hematologic parameters
- Caution patients against excessive alcohol intake, either acute or chronic, while receiving linagliptin/metformin therapy
Pregnancy Category:B
Breastfeeding: Because no information is available regarding linagliptin use during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Low levels of metformin are detectable in the serum of breastfed infants. Metformin levels in milk are relatively constant during maternal metformin use and infants receive <0.5% of the maternal weight-adjusted dosage. Use cautiously when nursing newborn/premature infants and those with renal impairment. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 09 February 2012). As per manufacturer's data, due to the potential risk of hypoglycemia in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug analyzing the importance of the drug to the mother.
US Trade Name(s)
US Availability
Jentadueto (linagliptin/metformin)
- TABS:
- 2.5 mg/500 mg
- 2.5 mg/850 mg
- 2.5 mg/1000 mg
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability