Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

JENTADUETO/JENTADUETO XR should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

JENTADUETO/JENTADUETO XR has 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 JENTADUETO/ JENTADUETO XR.

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.

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. If metformin-associated lactic acidosis is suspected, immediately discontinue JENTADUETO/JENTADUETO XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

The dosage of JENTADUETO should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended dose of 2.5 mg linagliptin/1000 mg metformin hydrochloride (HCl) twice daily. JENTADUETO should be given twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with metformin use.

JENTADUETO/JENTADUETO XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m².

Initiation of JENTADUETO/JENTADUETO XR  in patients with an-eGFR between 30 45 mL/min/1.73 m² is not recommended.

In patients taking JENTADUETO/JENTADUETO XR whose eGFR later falls below 45 mL/min/1.73 m², assess benefit risk of continuing therapy.

Discontinue JENTADUETO/JENTADUETO XR if the patient’s eGFR later falls below 30 mL/min/1.73 m².

Discontinue JENTADUETO 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 m²; 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 JENTADUETO/JENTADUETO XR if renal function is stable.

JENTADUETO/JENTADUETO XR is contraindicated in patients with:

• Severe renal impairment (eGFR below 30 mL/min/1.73 m²
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin 
• A history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity 
• Hypersensitivity to metformin

There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue JENTADUETO/JENTADUETO XR 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 JENTADUETO/JENTADUETO XR.

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.

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 JENTADUETO/JENTADUETO XR.

Reports of decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors.

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 JENTADUETO/JENTADUETO XR.

Insulin secretagogues and insulin are known to cause hypoglycemia. The risk of hypoglycemia is increased when JENTADUETO is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with JENTADUETO.

Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as SUs and insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking β-adrenergic blocking drugs.

Carbonic Anhydrase Inhibitors: 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 JENTADUETO/JENTADUETO XR  may increase the risk of lactic acidosis.

Drugs that Reduce Metformin Clearance: 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.

Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving JENTADUETO/ JENTADUETO XR.

Drug Interactions with Linagliptin: Inducers of P-glycoprotein and CYP3A4 Enzymes Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gp inducer or CYP3A4 inducer. As JENTADUETO/JENTADUETO XR is a fixed-dose combination of linagliptin and metformin, use of alternative treatments (not containing linagliptin) is strongly recommended when concomitant treatment with a strong P-gp or CYP3A4 inducer is necessary.

Co-administration of JENTADUETO/JENTADUETO XR with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

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. When such drugs are administered to a patient receiving JENTADUETO/ JENTADUETO XR, the patient should be closely observed to maintain adequate glycemic control. When such drugs are withdrawn from a patient receiving JENTADUETO/JENTADUETO XR, the patient should be observed closely for hypoglycemia.

Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women.

Published data from post-marketing 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 studies: increased incidence of fetal rib and scapula malformations.

Limited published studies report that metformin is present in human milk.

GoToSource JENTADUETO
GoToSource JENTADUETO XR

• Use in patients under the age of 18. GoToSource

Hypoglycemia (low blood sugar). GoToSource

Acute pancreatitis (inflammation of the pancreas). GoToSource

Liver injury. GoToSource

Severe and disabling arthralgia (joint pain). GoToSource

Skin blisters and ulcers. GoToSource

Lactic acidosis (too much acid in the body). GoToSource

Increased risk of worsening heart failure. GoToSource

Vitamin B12 deficiency. GoToSource

Lawsuits filed for bullous pemphigoid, pancreatic cancer, pancreatitis and rhabdomyolysis.