Trayenta Duo Actions

• Actions of Trayenta Duo in details
• Trayenta Duo administration
• Trayenta Duo pharmacology
• Trayenta Duo reviews

Actions of Trayenta Duo in details

Trayenta Duo

Trayenta Duo combines 2 antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: Linagliptin (Trayenta Duo), a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin (Trayenta Duo), a member of the biguanide class.

Linagliptin (Trayenta Duo)

Linagliptin (Trayenta Duo) 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). Thus, Linagliptin (Trayenta Duo) increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output.

Metformin (Trayenta Duo)

Metformin (Trayenta Duo) is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin (Trayenta Duo) decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike SUs, Metformin (Trayenta Duo) does not produce hypoglycemia in either patients with type 2 diabetes mellitus or normal subjects (except in special circumstances) and does not cause hyperinsulinemia. With Metformin (Trayenta Duo) therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

How should I take Trayenta Duo?

Your doctor will tell you how much of Trayenta Duo to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.

Trayenta Duo usually comes with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Carefully follow the special meal plan your doctor gave you. This is the most important part of controlling your diabetes, and is necessary if the medicine is to work properly. Exercise regularly and test for sugar in your blood or urine as directed.

Take Trayenta Duo with meals.

Dosing

The dose of Trayenta Duo will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Trayenta Duo. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For type 2 diabetes:
    • Adults:
      • Patients taking Metformin (Trayenta Duo) alone—The Metformin (Trayenta Duo) dose is the same as the dose you are already taking. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 2.5 milligrams (mg) of Linagliptin (Trayenta Duo) and 1000 mg of Metformin (Trayenta Duo) two times a day.
      • Patients taking Linagliptin (Trayenta Duo) alone—At first, one tablet containing 2.5 mg of Linagliptin (Trayenta Duo) and 500 mg of Metformin (Trayenta Duo) two times a day. Your doctor may gradually increase your dose until your blood sugar is controlled. However, the dose is usually not more than 2.5 mg of Linagliptin (Trayenta Duo) and 1000 mg of Metformin (Trayenta Duo) two times a day.
      • Patients taking Trayenta Duo as separate components—The Trayenta Duo dose are the same as the dose you are already taking. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 2.5 mg of Linagliptin (Trayenta Duo) and 1000 mg of Metformin (Trayenta Duo) two times a day.
    • Children—Use and dose must be determined by your doctor. :

Missed Dose

If you miss a dose of Trayenta Duo, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Trayenta Duo administration

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office.

Take Trayenta Duo twice daily with meals, unless your doctor tells you otherwise.

Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremor, irritability, or trouble concentrating.

Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection.

Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change.

Ask your doctor how to adjust your Trayenta Duo dose if needed. Do not change your medication dose or schedule without your doctor's advice.

Your doctor may have you take extra vitamin B12 while you are taking Metformin (Trayenta Duo). Take only the amount of vitamin B12 that your doctor has prescribed.

Trayenta Duo is only part of a complete program of treatment that may also include diet, exercise, weight control, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

Store at room temperature away from moisture and heat.

Trayenta Duo pharmacology

Mechanism Of Action

Trayenta Duo

Trayenta Duo combines 2 antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: Linagliptin (Trayenta Duo), a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin (Trayenta Duo), a member of the biguanide class.

Linagliptin (Trayenta Duo)

Linagliptin (Trayenta Duo) 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). Thus, Linagliptin (Trayenta Duo) increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output.

Metformin (Trayenta Duo)

Metformin (Trayenta Duo) is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin (Trayenta Duo) decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike SUs, Metformin (Trayenta Duo) does not produce hypoglycemia in either patients with type 2 diabetes mellitus or normal subjects (except in special circumstances) and does not cause hyperinsulinemia. With Metformin (Trayenta Duo) therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Pharmacodynamics

Linagliptin (Trayenta Duo)

Linagliptin (Trayenta Duo) binds to DPP-4 in a reversible manner and increases the concentrations of incretin hormones. Linagliptin (Trayenta Duo) glucose-dependently increases insulin secretion and lowers glucagon secretion, thus resulting in a better regulation of the glucose homeostasis. Linagliptin (Trayenta Duo) binds selectively to DPP-4 and selectively inhibits DPP-4, but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

Cardiac Electrophysiology

In a randomized, placebo-controlled, active-comparator, 4-way crossover study, 36 healthy subjects were administered a single oral dose of Linagliptin (Trayenta Duo) 5 mg, Linagliptin (Trayenta Duo) 100 mg (20 times the recommended dose), moxifloxacin, and placebo. No increase in QTc was observed with either the recommended dose of 5 mg or the 100-mg dose. At the 100-mg dose, peak Linagliptin (Trayenta Duo) plasma concentrations were approximately 38-fold higher than the peak concentrations following a 5-mg dose.

Pharmacokinetics

Trayenta Duo

The results of a bioequivalence study in healthy subjects demonstrated that Trayenta Duo (Trayenta Duo hydrochloride) 2.5 mg/500 mg, 2.5 mg/850 mg, and 2.5 mg/1000 mg combination tablets are bioequivalent to coadministration of corresponding doses of Trayenta Duo as individual tablets. Administration of Linagliptin (Trayenta Duo) 2.5 mg/Metformin (Trayenta Duo) hydrochloride 1000 mg fixed-dose combination with food resulted in no change in overall exposure of Linagliptin (Trayenta Duo). There was no change in Metformin (Trayenta Duo) AUC; however, mean peak serum concentration of Metformin (Trayenta Duo) was decreased by 18% when administered with food. A delayed time-to-peak serum concentrations by 2 hours was observed for Metformin (Trayenta Duo) under fed conditions. These changes are not likely to be clinically significant.

Absorption

Linagliptin (Trayenta Duo)

The absolute bioavailability of Linagliptin (Trayenta Duo) is approximately 30%. Following oral administration, plasma concentrations of Linagliptin (Trayenta Duo) decline in at least a biphasic manner with a long terminal half-life ( > 100 hours), related to the saturable binding of Linagliptin (Trayenta Duo) to DPP-4. However, the prolonged elimination does not contribute to the accumulation of the drug. The effective half-life for accumulation of Linagliptin (Trayenta Duo), as determined from oral administration of multiple doses of Linagliptin (Trayenta Duo) 5 mg, is approximately 12 hours. After once-daily dosing, steady state plasma concentrations of Linagliptin (Trayenta Duo) 5 mg are reached by the third dose, and Cmax and AUC increased by a factor of 1.3 at steady-state compared with the first dose. Plasma AUC of Linagliptin (Trayenta Duo) increased in a less than dose-proportional manner in the dose range of 1 to 10 mg. The pharmacokinetics of Linagliptin (Trayenta Duo) is similar in healthy subjects and in patients with type 2 diabetes.

Metformin (Trayenta Duo)

The absolute bioavailability of a Metformin (Trayenta Duo) hydrochloride 500-mg tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of Metformin (Trayenta Duo) tablets 500 mg to 1500 mg, and 850 mg to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination.

Distribution

Linagliptin (Trayenta Duo)

The mean apparent volume of distribution at steady state following a single intravenous dose of Linagliptin (Trayenta Duo) 5 mg to healthy subjects is approximately 1110 L, indicating that Linagliptin (Trayenta Duo) extensively distributes to the tissues. Plasma protein binding of Linagliptin (Trayenta Duo) is concentration-dependent decreasing from about 99% at 1 nmol/L to 75% to 89% at ≥ 30 nmol/L, reflecting saturation of binding to DPP-4 with increasing concentration of Linagliptin (Trayenta Duo). At high concentrations, where DPP-4 is fully saturated, 70% to 80% of Linagliptin (Trayenta Duo) remains bound to plasma proteins and 20% to 30% is unbound in plasma. Plasma binding is not altered in patients with renal or hepatic impairment.

Metformin (Trayenta Duo)

The apparent volume of distribution (V/F) of Metformin (Trayenta Duo) following single oral doses of immediate-release Metformin (Trayenta Duo) hydrochloride tablets 850 mg averaged 654±358 L. Metformin (Trayenta Duo) is negligibly bound to plasma proteins, in contrast to SUs, which are more than 90% protein bound. Metformin (Trayenta Duo) partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of Metformin (Trayenta Duo) tablets, steady-state plasma concentrations of Metformin (Trayenta Duo) are reached within 24 to 48 hours and are generally < 1 mcg/mL. During controlled clinical trials of Metformin (Trayenta Duo), maximum Metformin (Trayenta Duo) plasma levels did not exceed 5 mcg/mL, even at maximum doses.

Metabolism

Linagliptin (Trayenta Duo)

Following oral administration, the majority (about 90%) of Linagliptin (Trayenta Duo) is excreted unchanged, indicating that metabolism represents a minor elimination pathway. A small fraction of absorbed Linagliptin (Trayenta Duo) is metabolized to a pharmacologically inactive metabolite, which shows a steady-state exposure of 13.3% relative to Linagliptin (Trayenta Duo).

Metformin (Trayenta Duo)

Intravenous single-dose studies in normal subjects demonstrate that Metformin (Trayenta Duo) is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion.

Excretion

Linagliptin (Trayenta Duo)

Following administration of an oral [C]Linagliptin (Trayenta Duo) 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. Renal clearance at steady state was approximately 70 mL/min.

Metformin (Trayenta Duo)

Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of Metformin (Trayenta Duo) elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

Specific Populations

Renal Impairment

Trayenta Duo: Studies characterizing the pharmacokinetics of Trayenta Duo after administration of Trayenta Duo in renally impaired patients have not been performed. Since Metformin (Trayenta Duo) is contraindicated in patients with renal impairment, use of Trayenta Duo is also contraindicated in patients with renal impairment (e.g., serum creatinine ≥ 1.5 mg/dL [males] or ≥ 1.4 mg/dL [females], or abnormal creatinine clearance).

Linagliptin (Trayenta Duo)

Under steady-state conditions, Linagliptin (Trayenta Duo) exposure in patients with mild renal impairment was comparable to healthy subjects. In patients with moderate renal impairment under steady-state conditions, mean exposure of Linagliptin (Trayenta Duo) increased (AUCτ,ss by 71% and Cmax by 46%) compared with healthy subjects. This increase was not associated with a prolonged accumulation half-life, terminal half-life, or an increased accumulation factor. Renal excretion of Linagliptin (Trayenta Duo) was below 5% of the administered dose and was not affected by decreased renal function.

Patients with type 2 diabetes mellitus and severe renal impairment showed steady-state exposure approximately 40% higher than that of patients with type 2 diabetes mellitus and normal renal function (increase in AUC by 42% and Cmax by 35%). For both type 2 diabetes mellitus groups, renal excretion was below 7% of the administered dose.

Metformin (Trayenta Duo)

In patients with decreased renal function (based on measured creatinine clearance), the plasma and blood half-life of Metformin (Trayenta Duo) is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance.

Hepatic Impairment

Trayenta Duo: Studies characterizing the pharmacokinetics of Trayenta Duo after administration of Trayenta Duo in hepatically impaired patients have not been performed. However, use of Metformin (Trayenta Duo) alone in patients with hepatic impairment has been associated with some cases of lactic acidosis. Therefore, use of Trayenta Duo is not recommended in patients with hepatic impairment.

Linagliptin (Trayenta Duo)

In patients with mild hepatic impairment (Child-Pugh class A) steady-state exposure (AUCτ,ss) of Linagliptin (Trayenta Duo) was approximately 25% lower and Cmax,ss was approximately 36% lower than in healthy subjects. In patients with moderate hepatic impairment (Child-Pugh class B), AUCss of Linagliptin (Trayenta Duo) was about 14% lower and Cmax,ss was approximately 8% lower than in healthy subjects. Patients with severe hepatic impairment (Child-Pugh class C) had comparable exposure of Linagliptin (Trayenta Duo) in terms of AUC0-24 and approximately 23% lower Cmax compared with healthy subjects. Reductions in the pharmacokinetic parameters seen in patients with hepatic impairment did not result in reductions in DPP-4 inhibition.

Metformin (Trayenta Duo) Hydrochloride

No pharmacokinetic studies of Metformin (Trayenta Duo) have been conducted in patients with hepatic impairment.

Body Mass Index (BMI)/Weight

Linagliptin (Trayenta Duo)

BMI/Weight had no clinically meaningful effect on the pharmacokinetics of Linagliptin (Trayenta Duo) based on a population pharmacokinetic analysis.

Gender

Linagliptin (Trayenta Duo)

Gender had no clinically meaningful effect on the pharmacokinetics of Linagliptin (Trayenta Duo) based on a population pharmacokinetic analysis.

Metformin (Trayenta Duo) Hydrochloride

Metformin (Trayenta Duo) pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2 diabetes mellitus when analyzed according to gender. Similarly, in controlled clinical studies in patients with type 2 diabetes mellitus, the antihyperglycemic effect of Metformin (Trayenta Duo) was comparable in males and females.

Geriatric

Trayenta Duo

Studies characterizing the pharmacokinetics of Trayenta Duo after administration of Trayenta Duo in geriatric patients have not been performed. Based on the Metformin (Trayenta Duo) component, Trayenta Duo treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced.

Linagliptin (Trayenta Duo)

Age did not have a clinically meaningful impact on the pharmacokinetics of Linagliptin (Trayenta Duo) based on a population pharmacokinetic analysis.

Metformin (Trayenta Duo) Hydrochloride

Limited data from controlled pharmacokinetic studies of Metformin (Trayenta Duo) in healthy elderly subjects suggest that total plasma clearance of Metformin (Trayenta Duo) is decreased, the half-life is prolonged, and Cmax is increased, compared with healthy young subjects. From these data, it appears that the change in Metformin (Trayenta Duo) pharmacokinetics with aging is primarily accounted for by a change in renal function.

Pediatric

Studies characterizing the pharmacokinetics of Trayenta Duo after administration of Trayenta Duo in pediatric patients have not yet been performed.

Race

Linagliptin (Trayenta Duo)

Race had no clinically meaningful effect on the pharmacokinetics of Linagliptin (Trayenta Duo) based on available pharmacokinetic data, including subjects of White, Hispanic, Black, and Asian racial groups.

Metformin (Trayenta Duo) Hydrochloride

No studies of Metformin (Trayenta Duo) pharmacokinetic parameters according to race have been performed. In controlled clinical studies of Metformin (Trayenta Duo) in patients with type 2 diabetes mellitus, the antihyperglycemic effect was comparable in Caucasians (n=249), Blacks (n=51), and Hispanics (n=24).

Drug Interactions

Pharmacokinetic drug interaction studies with Trayenta Duo have not been performed; however, such studies have been conducted with the individual components of Trayenta Duo (Trayenta Duo hydrochloride).

Linagliptin (Trayenta Duo)

In vitro Assessment of Drug Interactions

Linagliptin (Trayenta Duo) is a weak to moderate inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes and is not an inducer of CYP isozymes, including CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A11.

Linagliptin (Trayenta Duo) is a P-glycoprotein (P-gp) substrate, and inhibits P-gp mediated transport of digoxin at high concentrations. Based on these results and in vivo drug interaction studies, Linagliptin (Trayenta Duo) is considered unlikely to cause interactions with other P-gp substrates at therapeutic concentrations.

In vivo Assessment of Drug Interactions

Strong inducers of CYP3A4 or P-gp (e.g., rifampin) decrease exposure to Linagliptin (Trayenta Duo) to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to Linagliptin (Trayenta Duo) is strongly recommended. In vivo studies indicated evidence of a low propensity for causing drug interactions with substrates of CYP3A4, CYP2C9, CYP2C8, P-gp, and OCT. No dose adjustment of Linagliptin (Trayenta Duo) is recommended based on results of the described pharmacokinetic studies.

Table 2 : Effect of Coadministered Drugs on Systemic Exposure of Linagliptin (Trayenta Duo)

Initial Combination Therapy With Trayenta Duo vs Linagliptin (Trayenta Duo) In Treatment-Na

References

1. DailyMed. "LINAGLIPTIN; METFORMIN HYDROCHLORIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. NCIt. "Linagliptin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
3. NCIt. "Metformin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Trayenta Duo are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Trayenta Duo. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

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Information checked by Dr. Sachin Kumar, MD Pharmacology