Mediclarum
Medicine guide

Linagliptin and Metformin Hydrochloride

2.5 mg + 500 mg · Tablet, Film Coated

  • Prescription only
  • Biguanide
Made by
Novadoz Pharmaceuticals LLC

Quoted from the official source. Not yet reviewed by Mediclarum — the leaflet in your pack is authoritative.

At a glance

Quoted from the official label · 2025-11-04

What it is

Biguanide

Used for
  • Linagliptin and metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in
The label’s usual adult dose

The maximum recommended dosage is 2.5 mg linagliptin/1,000 mg metformin HCl twice daily ( 2.1 )

Full directions ↓
Serious warning

LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.

All warnings ↓
Good to know
  • Prescription only
  • FDA enforcement reports list no ongoing recall, and none from the last two years, for this product code · checked 2026-10-02
7other products contain Linagliptin and Metformin Hydrochloride — compare makers, forms and strengths

Every line above is selected, not written, from the official label. Nothing is reworded. DailyMed

What it is for

  • Linagliptin and metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in
  • adults with type 2 diabetes mellitus. Limitations of Use Linagliptin and metformin hydrochloride tablets are not recommended in patients with type 1 diabetes mellitus. Linagliptin and metformin hydrochloride tablets have 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 linagliptin and metformin hydrochloride tablets [see Warnings and Precautions (5.2 )]. Linagliptin and metformin hydrochloride tablets are a combination of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin hydrochloride (HCl), a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in
  • adults with type 2 diabetes mellitus ( 1 ) Limitations of Use
  • Not recommended in patients with type 1 diabetes mellitus ( 1 )
  • Has not been studied in patients with a history of pancreatitis ( 1 )

From the official label · 2025-11-04 · DailyMed

How it works

From this product’s own US prescribing label.

Linagliptin and Metformin Hydrochloride Linagliptin and metformin hydrochloride contains: linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin, a biguanide.

Linagliptin Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Half-life100 h
Mostly cleared after≈ 3 weeksfive half-lives — our arithmetic
How the body breaks it down

A small fraction of absorbed linagliptin is metabolized to a pharmacologically inactive metabolite, which shows a steady-state exposure of 13.3% relative to linagliptin.

How it leaves the body

Linagliptin: Following administration of an oral [14C] linagliptin dose to healthy subjects, approximately 85% of the administered radioactivity was eliminated via the enterohepatic system (80%) or urine (5%) within 4 days of dosing.

With food

Linagliptin and Metformin Hydrochloride Administration of linagliptin 2.5 mg/metformin HCl 1,000 mg fixed-dose combination with food resulted in no change in overall exposure of linagliptin.

Quoted from the prescribing label, sections “Mechanism of Action” and “Pharmacokinetics”. DailyMed · 2025-11-04

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

  • LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.
  • The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.
  • Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1) ].
  • Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
  • Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see Dosage and Administration (2.2) , Contraindications (4) , Warnings and Precautions (5.1) , Drug Interactions (7) , and Use in Specific Populations (8.6 , 8.7 )].
  • If metformin-associated lactic acidosis is suspected, immediately discontinue linagliptin and metformin hydrochloride and institute general supportive measures in a hospital setting.
  • Prompt hemodialysis is recommended [see Warnings and Precautions (5.1) ].
  • WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning.
  • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.
  • Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain.
  • Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
  • ( 5.1 ) Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment.
  • Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information.
  • ( 5.1 ) If lactic acidosis is suspected, discontinue linagliptin and metformin hydrochloride and institute general supportive measures in a hospital setting.
  • Prompt hemodialysis is recommended.
  • ( 5.1 )

Quoted from the official label, section “Boxed Warning”.

Do not take it if

  • Linagliptin and metformin hydrochloride are contraindicated in patients with:
  • severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1 )] .
  • acute or chronic metabolic acidosis, including diabetic ketoacidosis [see Warnings and Precautions (5.1 )].
  • hypersensitivity to linagliptin, metformin, or any of the excipients in linagliptin and metformin hydrochloride, reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred with linagliptin [see Warnings and Precautions (5.4 ) and Adverse Reactions (6.1 )] . Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) ( 4 ) Metabolic acidosis, including diabetic ketoacidosis ( 4 ) Hypersensitivity to linagliptin, metformin, or any of the excipients in linagliptin and metformin hydrochloride ( 4 )

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

  • Individualize the starting dosage of linagliptin and metformin hydrochloride tablets based on the patient's current regimen ( 2.1 )
  • The maximum recommended dosage is 2.5 mg linagliptin/1,000 mg metformin HCl twice daily ( 2.1 )
  • Take orally twice daily with meals, with gradual dosage escalation to reduce the gastrointestinal effects due to metformin ( 2.1 )
  • Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR) ( 2.2 ) o
  • Do not use in patients with eGFR below 30 mL/min/1.73 m 2 o Initiation is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 o Assess risk/benefit of continuing if eGFR falls below 45 mL/min/1.73 m 2 o Discontinue if eGFR falls below 30 mL/min/1.73 m 2
  • Linagliptin and metformin hydrochloride tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures ( 2.3 ) 2.1 Recommended Dosage and Administration The dosage of linagliptin and metformin hydrochloride tablets should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended dosage of 2.5 mg linagliptin/1,000 mg metformin hydrochloride (HCl), taken orally twice daily. Linagliptin and metformin hydrochloride tablets should be given twice daily with meals. Dosage escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with metformin use. Recommended starting dosage:
  • In patients currently not treated with metformin HCl, initiate treatment with 2.5 mg linagliptin/500 mg metformin HCl twice daily.
  • In patients already treated with metformin HCl, start with 2.5 mg linagliptin and the current dosage of metformin HCl taken at each of the two daily meals (e.g., a patient on metformin HCl 1,000 mg twice daily would be started on 2.5 mg linagliptin/1,000 mg metformin HCl twice daily with meals).
  • Patients already treated with linagliptin and metformin HCl individual components may be switched to linagliptin and metformin hydrochloride tablets containing the same dosages of each component. 2.2 Recommended Dosing in Renal Impairment Assess renal function prior to initiation of linagliptin and metformin hydrochloride tablets and periodically thereafter. Linagliptin and metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2 . Initiation of linagliptin and metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/min/1.73 m 2 is not recommended. In patients taking linagliptin and metformin hydrochloride tablets whose eGFR later falls below 45 mL/min/1.73 m 2 , assess benefit /risk of continuing therapy. Discontinue linagliptin and metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/min/1.73 m 2 [ see Contraindications (4) and Warnings and Precautions (5.1)] . 2.3 Discontinuation for Iodinated Contrast Imaging Procedures Discontinue linagliptin and metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/ 1.73 m 2 ; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart linagliptin and metformin hydrochloride tablets if renal function is stable [ see Warnings and Precautions (5.1 ) ].

Quoted from the official label, section “Dosage & Administration”.

Other warnings

  • Lactic acidosis:
  • See boxed warning ( 5.1 ) Pancreatitis:
  • There have been reports of acute pancreatitis, including fatal pancreatitis. If pancreatitis is suspected, promptly discontinue linagliptin and metformin hydrochloride. ( 5.2 ) Hypoglycemia:
  • Consider lowering the dosage of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating linagliptin and metformin hydrochloride ( 5.3 ) Hypersensitivity reactions:
  • Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema, and exfoliative skin conditions) have occurred with linagliptin and metformin hydrochloride. If hypersensitivity reactions occur discontinue linagliptin and metformin hydrochloride, treat promptly, and monitor until signs and symptoms resolve. ( 5.4 ) Vitamin B 12 deficiency:
  • Metformin may lower vitamin B 12 levels. Measure hematologic parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. ( 5.5 ) Arthralgia:
  • Severe and disabling arthralgia has been reported in patients taking linagliptin. Consider as a possible cause for severe joint pain and discontinue drug if appropriate. ( 5.6 ) Bullous pemphigoid :
  • There have been reports of bullous pemphigoid requiring hospitalization. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue linagliptin and metformin hydrochloride. ( 5.7 ) Heart failure:
  • Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits of linagliptin and metformin hydrochloride in patients who have known risk factors for heart failure. Monitor for signs and symptoms. ( 5.8 ) 5.1 Lactic Acidosis Metformin There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate:
  • pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of linagliptin and metformin hydrochloride. In linagliptin and metformin hydrochloride-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin is dialyzable, with clearance of up to 170 mL/min under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery. Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to discontinue linagliptin and metformin hydrochloride and report these symptoms to their healthcare provider. For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below:
  • Renal Impairment:
  • The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient’s renal function include [see Dosage and Administration (2.2 ) and Clinical Pharmacology (12.3 )] :
  • Before initiating linagliptin and metformin hydrochloride, obtain an estimated glomerular filtration rate (eGFR).
  • Linagliptin and metformin hydrochloride is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications (4) ].
  • Initiation of linagliptin and metformin hydrochloride is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 .
  • Obtain an eGFR at least annually in all patients taking linagliptin and metformin hydrochloride. In patients at increased risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently.
  • In patients taking linagliptin and metformin hydrochloride whose eGFR later falls below 45 mL/min/1.73 m 2 , assess the benefit and risk of continuing therapy. Drug Interactions:
  • The concomitant use of linagliptin and metformin hydrochloride with specific drugs may increase the risk of metformin-associated lactic acidosis:
  • those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance or increase metformin accumulation [see Drug Interactions (7 )]. Therefore, consider more frequent monitoring of patients. Age 65 or Greater:
  • The risk of metformin-associated lactic acidosis increases with the patient’s age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Assess renal function more frequently in elderly patients [see Use in Specific Populations (8.5 )]. Radiological Studies with Contrast:
  • Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. Stop linagliptin and metformin hydrochloride at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m 2 ; in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and restart linagliptin and metformin hydrochloride if renal function is stable. Surgery and Other Procedures:
  • Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension and renal impairment. Linagliptin and metformin hydrochloride should be temporarily discontinued while patients have restricted food and fluid intake. Hypoxic States:
  • Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur, discontinue linagliptin and metformin hydrochloride. Excessive Alcohol Intake:
  • Alcohol potentiates the effect of metformin on lactate metabolism and this may increase the risk of metformin-associated lactic acidosis. Warn patients against excessive alcohol intake while receiving linagliptin and metformin hydrochloride. Hepatic Impairment:
  • Patients with hepatic impairment have developed cases of metformin-associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels. Therefore,
  • avoid use of linagliptin and metformin hydrochloride in patients with clinical or laboratory evidence of hepatic disease. 5.2 Pancreatitis Acute pancreatitis, including fatal pancreatitis, has been reported in patients treated with linagliptin. In the CARMELINA trial [see Clinical Studies (14.2 )], acute pancreatitis was reported in 9 (0.3%) patients treated with linagliptin and in 5 (0.1%) patients treated with placebo. Two patients treated with linagliptin in the CARMELINA trial had acute pancreatitis with a fatal outcome. There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients treated with linagliptin. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue linagliptin and metformin hydrochloride and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using linagliptin and metformin hydrochloride. 5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin secretagogues and insulin are known to cause hypoglycemia. The risk of hypoglycemia is increased when linagliptin and metformin hydrochloride is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin [see Adverse Reactions (6.1 )] . Therefore, a lower dosage of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with linagliptin and metformin hydrochloride. 5.4 Hypersensitivity Reactions 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 predominantly within the first 3 months after initiation of treatment with linagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue linagliptin and metformin hydrochloride, assess for other potential causes for the event, and institute alternative treatment for diabetes mellitus. Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema to another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with linagliptin and metformin hydrochloride. 5.5 Vitamin B 12 Deficiency In metformin clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of metformin-treated patients. Such decrease, possibly due to interference with B 12 absorption from the B 12 -intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin or vitamin B 12 supplementation. Certain individuals (those with inadequate vitamin B 12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B 12 levels. Measure hematologic parameters on an annual basis and vitamin B 12 at 2 to 3 year intervals in patients on linagliptin and metformin hydrochloride and manage any abnormalities [see Adverse Reactions (6.1 )] . 5.6 Severe and Disabling Arthralgia There have been postmarketing reports of severe and disabling arthralgia in patients taking linagliptin. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate. 5.7 Bullous Pemphigoid Bullous pemphigoid was reported in 7 (0.2%) patients treated with linagliptin compared to none in patients treated with placebo in the CARMELINA trial [see Clinical Studies (14.2 )] , and 3 of these patients were hospitalized due to bullous pemphigoid. Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving linagliptin and metformin hydrochloride. If bullous pemphigoid is suspected, linagliptin and metformin hydrochloride should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment. 5.8 Heart Failure 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. These trials evaluated patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Consider the risks and benefits of linagliptin and metformin hydrochloride 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. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of linagliptin and metformin hydrochloride.

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

  • Risk Summary The limited data with linagliptin and metformin hydrochloride and linagliptin use in pregnant women are not sufficient to inform a linagliptin and metformin hydrochloride-associated or linagliptin-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 defector miscarriage risk [see Data].
  • There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations].
  • In animal reproduction studies, no adverse developmental effects were observed when the combination of linagliptin and metformin was administered to pregnant rats during the period of organogenesis at doses similar to the maximum recommended clinical dose, based on exposure [see Data].
  • The estimated background risk of major birth defects is 6% to10% in women with pre-gestational diabetes with a HbA1c>7 and has been reported to be as high as 20% to 25% in women with HbA1c>10.
  • The estimated background risk of miscarriage for the indicated population is unknown.
  • In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
  • Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications.
  • Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
  • Data Human Data Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy.
  • However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups.
  • Animal Data Linagliptin and metformin, the components of linagliptin and metformin hydrochloride, were coadministered to pregnant Wistar Han rats during the period of organogenesis.
  • No adverse developmental outcome was observed at doses similar to the maximum recommended clinical dose, based on exposure.
  • At higher doses associated with maternal toxicity, the metformin component of the combination was associated with an increased incidence of fetal rib and scapula malformations at ≥9-times a 2,000 mg clinical dose, based on exposure.
  • Linagliptin No adverse developmental outcome was observed when linagliptin was administered to pregnant Wistar Han rats and Himalayan rabbits during the period of organogenesis at doses up to 240 mg/kg/day and 150 mg/kg/day, respectively.
  • These doses represent approximately 943-times (rats) and 1,943-times (rabbits) the 5 mg maximum clinical dose, based on exposure.
  • No adverse functional, behavioral, or reproductive outcome was observed in offspring following administration of linagliptin to Wistar Han rats from gestation day 6 to lactation day 21 at a dose 49-times the maximum recommended human dose, based on exposure.
  • Linagliptin crosses the placenta into the fetus following oral dosing in pregnant rats and rabbits.
  • Metformin HCl Metformin HCl did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits at doses up to 600 mg/kg/day during the period of organogenesis.
  • This represents an exposure of approximately 2- and 6-times a clinical dose of 2,000 mg, based on body surface area (mg/m 2 ) for rats and rabbits, respectively.
  • IN SPECIFIC POPULATIONS Females and Males of Reproductive Potential:
  • Advise premenopausal females of the potential for an unintended pregnancy ( 8.3 ) Geriatric Use:
  • Assess renal function more frequently ( 8.5 ) Hepatic Impairment:
  • Avoid use in patients with hepatic impairment ( 8.7 )
  • 8.1 Pregnancy Risk Summary The limited data with linagliptin and metformin hydrochloride and linagliptin use in pregnant women are not sufficient to inform a linagliptin and metformin hydrochloride-associated or linagliptin-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 defector miscarriage risk [see Data].
  • There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations].
  • In animal reproduction studies, no adverse developmental effects were observed when the combination of linagliptin and metformin was administered to pregnant rats during the period of organogenesis at doses similar to the maximum recommended clinical dose, based on exposure [see Data].
  • The estimated background risk of major birth defects is 6% to10% in women with pre-gestational diabetes with a HbA1c>7 and has been reported to be as high as 20% to 25% in women with HbA1c>10.
  • The estimated background risk of miscarriage for the indicated population is unknown.
  • In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
  • Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications.
  • Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
  • Data Human Data Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy.
  • However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups.
  • Animal Data Linagliptin and metformin, the components of linagliptin and metformin hydrochloride, were coadministered to pregnant Wistar Han rats during the period of organogenesis.
  • No adverse developmental outcome was observed at doses similar to the maximum recommended clinical dose, based on exposure.
  • At higher doses associated with maternal toxicity, the metformin component of the combination was associated with an increased incidence of fetal rib and scapula malformations at ≥9-times a 2,000 mg clinical dose, based on exposure.
  • Linagliptin No adverse developmental outcome was observed when linagliptin was administered to pregnant Wistar Han rats and Himalayan rabbits during the period of organogenesis at doses up to 240 mg/kg/day and 150 mg/kg/day, respectively.
  • These doses represent approximately 943-times (rats) and 1,943-times (rabbits) the 5 mg maximum clinical dose, based on exposure.
  • No adverse functional, behavioral, or reproductive outcome was observed in offspring following administration of linagliptin to Wistar Han rats from gestation day 6 to lactation day 21 at a dose 49-times the maximum recommended human dose, based on exposure.
  • Linagliptin crosses the placenta into the fetus following oral dosing in pregnant rats and rabbits.
  • Metformin HCl Metformin HCl did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits at doses up to 600 mg/kg/day during the period of organogenesis.
  • This represents an exposure of approximately 2- and 6-times a clinical dose of 2,000 mg, based on body surface area (mg/m 2 ) for rats and rabbits, respectively.
  • 8.2 Lactation Risk Summary There is limited information regarding the presence of linagliptin and metformin hydrochloride or its components (linagliptin or metformin) in human milk, the effects on the breastfed infant, or the effects on milk production.
  • However, linagliptin is present in rat milk.
  • Limited published studies report that metformin is present in human milk [see Data].
  • Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for linagliptin and metformin hydrochloride and any potential adverse effects on the breastfed child from linagliptin and metformin hydrochloride or from the underlying maternal condition.
  • Data Published clinical lactation studies report that metformin is present in human milk which resulted in infant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.13 and 1.
  • However, the studies were not designed to definitely establish the risk of use of metformin during lactation because of small sample size and limited adverse event data collected in infants.
  • 8.3 Females and Males of Reproductive Potential Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women.
  • 8.4 Pediatric Use Safety and effectiveness of linagliptin and metformin hydrochloride have not been established in pediatric patients. "Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Jentadueto® (Linagliptin;
  • Metformin hydrochloride) Tablets.
  • However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information."
  • 8.5 Geriatric Use Linagliptin is minimally excreted by the kidney; however, metformin is substantially excreted by the kidney [see Warnings and Precautions (5.1 ) and Clinical Pharmacology (12.3) ] .
  • Linagliptin In linagliptin studies, 1,085 linagliptin-treated patients were 65 years of age and older and 131 patients were 75 years of age and older.
  • In these linagliptin studies, no overall differences in safety or effectiveness of linagliptin were observed between geriatric patients and younger adult patients.
  • Metformin Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients.
  • In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis.
  • Assess renal function more frequently in elderly patients [see Contraindications (4 ), Warnings and Precautions (5.1 ), and Clinical Pharmacology (12.3 )] .
  • 8.6 Renal Impairment Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment.
  • Linagliptin and metformin hydrochloride is contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2 [see Dosage and Administration (2.2 ), Contraindications (4 ), Warnings and Precautions (5.1 ), and Clinical Pharmacology (12.3 )].
  • In the linagliptin treatment arm of the CARMELINA trial [see Clinical Studies (14.2)], 2,200 (63%) patients had renal impairment (eGFR <60 mL/min/1.73 m 2 ).
  • Approximately 20% of the population had eGFR ≥45 to <60 mL/min/1.73 m 2 , 28% of the population had eGFR ≥30 to <45 mL/min/1.73 m 2 and 15% had eGFR <30 mL/min/1.73 m 2 .
  • The overall incidence of adverse reactions were generally similar between the linagliptin and placebo treatment arms.
  • 8.7 Hepatic Impairment Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis.
  • Linagliptin and metformin hydrochloride is not recommended in patients with hepatic impairment [see Warnings and Precautions (5.1) ].

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

  • Table 2 describes clinically relevant interactions with linagliptin and metformin hydrochloride.
  • Table 2 Clinically Relevant Interactions with linagliptin and metformin hydrochloride Carbonic Anhydrase Inhibitors Clinical Impact Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.
  • Concomitant use of these drugs with linagliptin and metformin hydrochloride may increase the risk of lactic acidosis.
  • Intervention Consider more frequent monitoring of these patients.
  • Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3 )].
  • Intervention Consider the benefits and risks of concomitant use.
  • Alcohol Clinical Impact Alcohol is known to potentiate the effect of metformin on lactate metabolism.
  • Intervention Warn patients against excessive alcohol intake while receiving linagliptin and metformin hydrochloride.
  • Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia is increased when linagliptin and metformin hydrochloride is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin.
  • Intervention Coadministration of linagliptin and metformin hydrochloride with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
  • Drugs Affecting Glycemic Control Clinical Impact Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control.
  • These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.
  • Intervention When such drugs are administered to a patient receiving linagliptin and metformin hydrochloride, the patient should be closely observed to maintain adequate glycemic control.
  • When such drugs are withdrawn from a patient receiving linagliptin and metformin hydrochloride, the patient should be observed closely for hypoglycemia.
  • Inducers of P-glycoprotein or CYP3A4 Enzymes Clinical Impact 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.
  • Intervention Use of alternative treatments is strongly recommended when linagliptin is to be administered with a strong P-gp or CYP3A4 inducer.
  • Carbonic Anhydrase Inhibitors: May increase risk of lactic acidosis.
  • Consider more frequent monitoring.
  • ( 7 ) Drugs that Reduce Metformin Clearance: May increase risk of lactic acidosis.
  • Consider benefits and risks of concomitant use.
  • (7 ) Alcohol: Can potentiate the effect of metformin on lactate metabolism.
  • Warn patients against excessive alcohol intake.
  • ( 7 ) Strong P-glycoprotein/CYP3A4 Inducer:
  • Efficacy may be reduced when administered in combination (e.g., rifampin).
  • Use of alternative treatments is strongly recommended.
  • ( 7 )

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

  • In the event of an overdose with linagliptin and metformin hydrochloride, consider contacting the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdosage management recommendations.
  • Overdose of metformin HCl has occurred, including ingestion of amounts greater than 50 grams.
  • Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1 )].
  • Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions.
  • Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
  • Removal of linagliptin by hemodialysis or peritoneal dialysis is unlikely.

Quoted from the official label, section “Overdosage”.

Use in children

  • Safety and effectiveness of linagliptin and metformin hydrochloride have not been established in pediatric patients. "Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Boehringer Ingelheim Pharmaceuticals, Inc.’s Jentadueto® (Linagliptin;
  • Metformin hydrochloride) Tablets.
  • However, due to Boehringer Ingelheim Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information."

Quoted from the official label, section “Pediatric Use”.

Use in older people

  • Linagliptin is minimally excreted by the kidney; however, metformin is substantially excreted by the kidney [see Warnings and Precautions (5.1 ) and Clinical Pharmacology (12.3) ] .
  • Linagliptin In linagliptin studies, 1,085 linagliptin-treated patients were 65 years of age and older and 131 patients were 75 years of age and older.
  • In these linagliptin studies, no overall differences in safety or effectiveness of linagliptin were observed between geriatric patients and younger adult patients.
  • Metformin Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients.
  • In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis.
  • Assess renal function more frequently in elderly patients [see Contraindications (4 ), Warnings and Precautions (5.1 ), and Clinical Pharmacology (12.3 )] .

Quoted from the official label, section “Geriatric Use”.

Side effects

  • The following serious adverse reactions are described below or elsewhere in the prescribing information:
  • Lactic Acidosis [see Warnings and Precautions (5.1 )]
  • Pancreatitis [see Warnings and Precautions (5.2 )]
  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.3 )]
  • Hypersensitivity Reactions [see Warnings and Precautions (5.4 )]
  • Vitamin B 12 Deficiency [see Warnings and Precautions (5.5 )]
  • Severe and Disabling Arthralgia [see Warnings and Precautions (5.6 )]
  • Bullous Pemphigoid [see Warnings and Precautions (5.7 )]
  • Heart Failure [see Warnings and Precautions (5.8 )] Most common adverse reactions (incidence ≥5% and more often than placebo) were nasopharyngitis and diarrhea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Linagliptin/Metformin The safety of concomitantly administered linagliptin (daily dosage 5 mg) and metformin (mean daily dosage of approximately 1,800 mg) has been evaluated in 2,816 patients with type 2 diabetes mellitus treated for ≥12 weeks in clinical trials. Three placebo-controlled trials with linagliptin + metformin were conducted:
  • 2 studies were 24 weeks in duration, 1 trial was 12 weeks in duration. In the 3 placebo-controlled clinical studies, adverse reactions which occurred in ≥5% of patients receiving linagliptin + metformin (n=875) and were more common than in patients given placebo+ metformin (n=539) included nasopharyngitis (5.7% vs 4.3%). In a 24-week factorial design trial, adverse reactions reported in ≥5% of patients receiving linagliptin + metformin and were more common than in patients given placebo are shown in Table 1. Table 1 Adverse Reactions Reported in ≥5% of Patients Treated with Linagliptin + Metformin and Greater than with Placebo in a 24-week Factorial-Design Trial Adverse Reactions Placebo (%) n =72 Li n a g li pt in M o n o th er a py (%) n =142 M e tf or m i n M o n o th er a py (%) n =291 C o m b i n a t io n of Li n a g li pt i n with Metformin(%) n =286 Nasopharyngitis 1.4 5.6 2.7 6.3 Diarrhea 2.8 3.5 3.8 6.3 Other adverse reactions reported in clinical studies with treatment of linagliptin + metformin were hypersensitivity (e.g., urticaria, angioedema, or bronchial hyperreactivity), cough, decreased appetite, nausea, vomiting, pruritus, and pancreatitis. Linagliptin Adverse reactions reported in ≥2% of patients treated with linagliptin 5 mg and more commonly than in patients treated with placebo included:
  • nasopharyngitis (7% vs 6.1%), diarrhea (3.3% vs 3%), and cough (2.1% vs 1.4%). Rates for other adverse reactions for linagliptin 5 mg vs placebo when linagliptin was used in combination with specific anti-diabetic agents were:
  • urinary tract infection (3.1% vs 0%) and hypertriglyceridemia (2.4% vs 0%) when linagliptin was used as add-on to sulfonylurea; hyperlipidemia (2.7% vs 0.8%) and weight increased (2.3% vs 0.8%) when linagliptin was used as add-on to pioglitazone; and constipation (2.1% vs 1%) when linagliptin was used as add-on to basal insulin therapy. Other adverse reactions reported in clinical studies with treatment of linagliptin monotherapy were hypersensitivity (e.g., urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity) and myalgia. In the clinical trial program, pancreatitis was reported in 15.2 cases per 10,000 patient year exposure while being treated with linagliptin compared with 3.7 cases per 10,000 patient year exposure while being treated with comparator (placebo and active comparator, sulfonylurea). Three additional cases of pancreatitis were reported following the last administered dose of linagliptin. Metformin The most common (>5%) adverse reactions due to initiation of metformin therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache. Other Adverse Reactions Hypoglycemia Linagliptin/Metformin In a 24-week factorial design trial, hypoglycemia was reported in 4 (1.4%) of 286 subjects treated with linagliptin + metformin, 6 (2.1%) of 291 subjects treated with metformin, and 1 (1.4%) of 72 subjects treated with placebo. The incidence of hypoglycemia with plasma glucose <54 mg/dL was 8.1% in the linagliptin group (N=792) compared to 5.3% in the placebo group (N=263) when administered in combination with metformin and sulfonylurea in a 24-week trial. Linagliptin The incidence of severe hypoglycemia (requiring assistance) was 1.7% in the linagliptin group (N=631) compared to 1.1% in the placebo group (N=630) when administered in combination with basal insulin in a 52-week trial. Laboratory Test Abnormalities in Clinical Trials of Linagliptin or Metformin Linagliptin Increase in Uric Acid:
  • Changes in laboratory values that occurred more frequently in the linagliptin group and ≥1% more than in the placebo group were increases in uric acid (1.3% in the placebo group, 2.7% in the linagliptin group). Increase in Lipase:
  • In a placebo-controlled clinical trial with linagliptin in type 2 diabetes mellitus patients with micro- or macroalbuminuria, a mean increase of 30% in lipase concentrations from baseline to 24 weeks was observed in the linagliptin arm compared to a mean decrease of 2% in the placebo arm. Lipase levels above 3 times upper limit of normal were seen in 8.2% compared to 1.7% patients in the linagliptin and placebo arms, respectively. Increase in Amylase:
  • In a cardiovascular safety trial comparing linagliptin versus glimepiride in patients with type 2 diabetes mellitus, amylase levels above 3 times upper limit of normal were seen in 1% compared to 0.5% of patients in the linagliptin and glimepiride arms, respectively. The clinical significance of elevations in lipase and amylase with linagliptin is unknown in the absence of potential signs and symptoms of pancreatitis [see Warnings and Precautions (5.2 )]. Metformin Decrease in Vitamin B 12 :
  • In metformin clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients . 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Linagliptin
  • Gastrointestinal Disorders:
  • Acute pancreatitis, including fatal pancreatitis [see Indications and Usage (1 )] , mouth ulceration, stomatitis
  • Immune System Disorders:
  • Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions
  • Musculoskeletal and Connective Tissue Disorders:
  • Rhabdomyolysis, severe and disabling arthralgia
  • Skin and Subcutaneous Tissue Disorders: Bullous pemphigoid, rash Metformin
  • Hepatobiliary Disorders:
  • Cholestatic, hepatocellular, and mixed hepatocellular liver injury

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

  • Advise the patient to read the FDA-approved patient labeling (Medication Guide) Lactic Acidosis Inform patients of the risks of lactic acidosis due to metformin, its symptoms, and conditions that predispose to its development.
  • Advise patients to discontinue linagliptin and metformin hydrochloride immediately and to notify their healthcare provider promptly if unexplained hyperventilation, malaise, myalgia, unusual somnolence, or other nonspecific symptoms occur.
  • Counsel patients against excessive alcohol intake and inform patients about importance of regular testing of renal function while receiving linagliptin and metformin hydrochloride.
  • Instruct patients to inform their healthcare provider that they are taking linagliptin and metformin hydrochloride prior to any surgical or radiological procedure, as temporary discontinuation may be required until renal function has been confirmed to be normal [see Warnings and Precautions (5.1 )].
  • Pancreatitis Inform patients that acute pancreatitis has been reported during use of linagliptin.
  • Inform patients that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis.
  • Instruct patients to discontinue linagliptin and metformin hydrochloride promptly and contact their healthcare provider if persistent severe abdominal pain occurs [see Warnings and Precautions (5.2 )].
  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Inform patients that the risk of hypoglycemia is increased when linagliptin and metformin hydrochloride is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin [see Warnings and Precautions (5.3 )].
  • Hypersensitivity Reactions Inform patients that serious allergic reactions, such as anaphylaxis, angioedema, and exfoliative skin conditions, have been reported during postmarketing use of linagliptin (one of the components of linagliptin and metformin hydrochloride).
  • If symptoms of allergic reactions (such as rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking linagliptin and metformin hydrochloride and seek medical advice promptly [see Warnings and Precautions (5.4 )] .
  • Vitamin B 12 Deficiency Inform patients about the importance of regular hematological parameters while receiving linagliptin and metformin hydrochloride [see Warnings and Precautions (5.5 )].
  • Severe and Disabling Arthralgia Inform patients that severe and disabling joint pain may occur with this class of drugs.
  • The time to onset of symptoms can range from one day to years.
  • Instruct patients to seek medical advice if severe joint pain occurs [see Warnings and Precautions (5.6 )].
  • Bullous Pemphigoid Inform patients that bullous pemphigoid has been reported during use of linagliptin.
  • Instruct patients to seek medical advice if blisters or erosions occur [see Warnings and Precautions (5.7 )] .
  • Heart Failure Inform patients of the signs and symptoms of heart failure.
  • Before initiating linagliptin and metformin hydrochloride, patients should be asked about a history of heart failure or other risk factors for heart failure including moderate to severe renal impairment.
  • Instruct patients to contact their healthcare provider as soon as possible if they experience symptoms of heart failure, including increasing shortness of breath, rapid increase in weight or swelling of the feet [see Warnings and Precautions (5.8 )].
  • Patients of Reproductive Potential Inform patients that treatment with metformin may result in ovulation in some premenopausal anovulatory patients, which may lead to unintended pregnancy [see Use in Specific Populations (8.3) ].
  • Missed Dose Instruct patients to take linagliptin and metformin hydrochloride only as prescribed.
  • If a dose is missed, it should be taken as soon as the patient remembers.
  • Advise patients not to double their next dose.
  • Manufactured by:
  • MSN Laboratories Private Limited Telangana - 509 228, INDIA Distributed by:
  • Novadoz Pharmaceuticals LLC Piscataway, NJ 08854 -3714 The brands listed are trademarks or registered trademarks of their respective owners and are not affiliated with and do not endorse Novadoz Pharmaceuticals LLC.
  • Issued: 11/2025

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

  • FORMS AND STRENGTHS Linagliptin and metformin hydrochloride tablets are a combination of linagliptin and metformin hydrochloride available as:
  • 2.5 mg linagliptin/500 mg metformin hydrochloride tablets are yellow, oval, biconvex film-coated tablets debossed with "500" on one side and "LM" on the other side 2.5 mg linagliptin/850 mg metformin hydrochloride tablets are orange, oval, biconvex film-coated tablets debossed with "850" on one side and "LM" on the other side 2.5 mg linagliptin/1,000 mg metformin hydrochloride tablets are pink, oval, biconvex film-coated tablets debossed with "1,000" on one side and "LM" on the other side Tablets:
  • 2.5 mg linagliptin/500 mg metformin hydrochloride ( 3 ) 2.5 mg linagliptin/850 mg metformin hydrochloride ( 3 ) 2.5 mg linagliptin/1,000 mg metformin hydrochloride ( 3 )

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

  • Linagliptin and metformin hydrochloride tablets 2.5 mg/500 mg are yellow, oval, biconvex film-coated tablets debossed with “500” on one side and “LM” on the other side, and are supplied as follows:
  • Bottles of 60 (NDC 72205-407-01) Bottles of 180 (NDC 72205-407-02) Linagliptin and metformin hydrochloride tablets 2.5 mg/850 mg are orange, oval, biconvex film-coated tablets debossed with “850” on one side and “LM” on the other side, and are supplied as follows:
  • Bottles of 60 (NDC 72205-408-01) Bottles of 180 (NDC 72205-408-02) Linagliptin and metformin hydrochloride tablets 2.5 mg/1,000 mg are pink, oval, biconvex film-coated tablets debossed with “1000” on one side and “LM” on the other side, and are supplied as follows:
  • Bottles of 60 (NDC 72205-409-01) Bottles of 180 (NDC 72205-409-02) Storage
  • Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
  • Protect from exposure to high humidity.

Quoted from the official label, section “How Supplied”.

What is in it

  • Linagliptin and metformin hydrochloride tablets for oral use contain:
  • linagliptin and metformin hydrochloride. Linagliptin Linagliptin is an inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. The chemical name of linagliptin is 1H-Purine-2,6-dione, 8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]- The molecular formula is C 25 H 28 N 8 O 2 and the molecular weight is 472.54 g/mol. The structural formula is:
  • Linagliptin is a white to yellowish, not or only slightly hygroscopic solid substance. It is very slightly soluble in water (0.9 mg/mL). Linagliptin is soluble in methanol (ca. 60 mg/mL), sparingly soluble in ethanol (ca. 10 mg/mL), very slightly soluble in isopropanol (<1 mg/mL), and very slightly soluble in acetone (ca.1 mg/mL). Metformin Hydrochloride Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is a biguanide. Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5
  • HCl and a molecular weight of 165.63 g/mol. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is:
  • Linagliptin and Metformin Hydrochloride Tablets Linagliptin and metformin hydrochloride tablets are available for oral administration as tablets containing:
  • 2.5 mg linagliptin and 500 mg metformin hydrochloride (equivalent to 389.93 mg of metformin)
  • 2.5 mg linagliptin and 850 mg metformin hydrochloride (equivalent 662.88 mg of metformin)
  • 2.5 mg linagliptin and 1,000 mg metformin hydrochloride (equivalent to 779.86 mg of metformin) Each film-coated tablet of linagliptin and metformin hydrochloride tablets contains the following inactive ingredients:
  • colloidal silicon dioxide, copovidone, corn starch, hypromellose, magnesium stearate, meglumine, povidone, propylene glycol, titanium dioxide, talc, yellow iron oxide (2.5 mg/500 mg; 2.5 mg/850 mg) and/or red iron oxide (2.5 mg/850 mg; 2.5 mg/1,000 mg). lina-met-tabs-structure1 lina-met-tabs-structure2

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

  • Titanium dioxidetitanium dioxideA whitening agent no longer allowed in food in the EU (E171).

Quoted from the FDA label. A label that does not name an ingredient is not a guarantee that the product is free of it, and formulations change. With an allergy, check the pack and ask a pharmacist.

Every version of this medicine (2)

The same active substance, strength and kind of form, from every company that sells it — with what each label lists.

Hide versions whose label lists:

Showing 2 of 2

Same active substance, strength and form in other countries

Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.

Medicine passport: one printable page to show a pharmacist abroad

European UnionNo exact match for this strength and form

Every strength and form (1)

Canada1 matching products

Every strength and form (3)

Details

Made byNovadoz Pharmaceuticals LLC
Active substanceLinagliptin and Metformin Hydrochloride
Used inDigestion, stomach, diabetes and nutrition
Strength2.5 mg + 500 mg
FormTablet, Film Coated
RouteOral
Packs60 TABLET, FILM COATED in 1 BOTTLE · 180 TABLET, FILM COATED in 1 BOTTLE
NDC72205-407

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

Report wrong or outdated information on this page

Other strengths and forms

3 products are sold under this name. Grouped by form; a number on a strength means several companies make it.

Same active substance

These contain the same substance. That does not mean one can replace another — ask a pharmacist.

Jentadueto2.5 mg + 500 mgPrescription onlyTablet, Film Coated Boehringer Ingelheim Pharmaceuticals, Inc. · Linagliptin and Metformin HydrochlorideJentadueto2.5 mg + 850 mgPrescription onlyTablet, Film Coated Boehringer Ingelheim Pharmaceuticals, Inc. · Linagliptin and Metformin HydrochlorideJentadueto2.5 mg + 1000 mgPrescription onlyTablet, Film Coated Boehringer Ingelheim Pharmaceuticals, Inc. · Linagliptin and Metformin HydrochlorideJentadueto Xr2.5 mg + 1000 mgPrescription onlyTablet, Film Coated, Extended Release Boehringer Ingelheim Pharmaceuticals, Inc. · Linagliptin and Metformin HydrochlorideJentadueto Xr5 mg + 1000 mgPrescription onlyTablet, Film Coated, Extended Release Boehringer Ingelheim Pharmaceuticals, Inc. · Linagliptin and Metformin HydrochlorideLinagliptin and Metformin Hydrochloride2.5 mg + 850 mgPrescription onlyTablet, Film Coated Novadoz Pharmaceuticals LLC · Linagliptin and Metformin Hydrochloride

See every product with Linagliptin and Metformin Hydrochloride