What Are the Uses of Glimepiride and Pioglitazone?

Ligliptin tablets, suitable for the treatment of type 2 diabetes.

Drug Name: Ligliptin tablets
Whether prescription drugs: prescription
Main indications: Type 2 diabetes
Dosage: 5mg / tablet, once daily
Adverse reactions: Adverse event rates are similar to placebo
Main medication contraindications: Disabled in patients with a history of allergies to ligagliptin

Dosage form: tablet
Athletes use with caution: Inadvertent use
Whether to include health insurance: Incorporate
Approval Number: Import Drug Registration Certificate Number: H20130865, H20130899, H20130890
Drug type: prescription
Use classification: Endocrinology and Metabolism
Hanyu Pinyin: Li Ge Lie Ting Pian

Ligliptin tablets ingredients

Chemical name: 8-[(3R) -3-amino-1-piperidinyl] -7- (2-butynyl-1) -3,7-dihydro-3-methyl-1-[(4 -Methyl-2-quinazolinyl) methyl] -1H-purine-2,6-dione.

Chemical Structure

[Molecular formula] C ₂₅ H ₂₈ N ₈ O ₂

[Molecular weight] 472.54

Ligliptin Tablet Properties

This product is a light red round biconvex, beveled film-coated tablet. One side is engraved with the BI company logo and the other side is engraved with "D5". After removing the coating, it is white or off-white.

Ligliptin Tablets Specifications

5 mg.

Ligliptin Tablets

tablet

Ligliptin Tablets Packaging

Double aluminum blister pack.

7 pieces / box (1 plate × 7 pieces / board), 14 pieces / box (2 plates × 7 pieces / board), 28 pieces / box (4 plates × 7 pieces / board), 10 pieces / box (1 plate × 10 tablets / board), 30 tablets / box (3 plates × 10 tablets / board), 60 tablets / box (6 plates × 10 tablets / board).

Ligliptin tablets indications

This product is suitable for the treatment of type 2 diabetes.

Monotherapy

This product is used as an adjunct to diet control and exercise to improve blood sugar control in patients with type 2 diabetes.

Used in combination with metformin hydrochloride

When metformin hydrochloride alone cannot effectively control blood sugar, this product can be used in combination with metformin hydrochloride to improve blood glucose control in patients with type 2 diabetes based on diet and exercise.

Used in combination with metformin hydrochloride and sulfonylureas

When metformin hydrochloride and sulfonylurea drugs cannot effectively control blood sugar, this product can be used in combination with metformin hydrochloride and sulfonylurea drugs to improve blood glucose control in patients with type 2 diabetes based on diet and exercise.

Ligliptin tablets dosage

adult

The recommended dose is 5 mg once daily. This product can be taken at any time of the day, with or without meals.

Special population:

Patients with renal insufficiency

Patients with renal insufficiency do not need to adjust the dose.

Patients with liver dysfunction

Patients with liver dysfunction do not need to adjust the dose.

Missed

If missed doses, patients are advised not to take double doses at the next dose.

Adverse effects of Ligliptin tablets

Clinical trial experience

Because the conditions of clinical trials are very different, the rate of adverse reactions observed in the clinical trials of one drug cannot be directly compared with the incidence in the clinical trials of another drug and may not reflect the clinical Incidence observed in practice.

Fourteen placebo-controlled studies, an active-drug controlled study, and a study in patients with severe renal insufficiency evaluated the safety of rigagliptin 5 mg once daily in patients with type 2 diabetes.

In three placebo-controlled trials with durations of 18 and 24 weeks and five supplemental placebo-controlled trials with duration of less than 18 weeks, rigagliptin 5 mg was administered once a day as a monotherapy the study. Ritagliptin was studied in combination with other hypoglycemic agents in six placebo-controlled trials: two in combination with metformin (treatment duration of 12 and 24 weeks); one in combination with sulfonylurea (treatment duration 18 weeks); one combined with metformin and sulfonylurea (treatment duration 24 weeks); one combined with pioglitazone (treatment duration 24 weeks); and one combined with insulin (primary endpoint at 24 weeks) ).

In a pooled data set of 14 placebo-controlled clinical trials, 2% of patients who received lidagliptin (n = 3625) occurred and were more common than those who received placebo (n = 2176) See Table 1 for adverse events.

The overall incidence of adverse events with lidagliptin was similar to placebo.

Table 1 In placebo-controlled studies with single-agent or combination-statin Ligliptin, patients treated with Ligliptin reported an incidence of 2% and higher adverse effects than placebo

	Number of patients (%)
	Ligliptin 5mg n = 3625	Placebo n = 2176
Nasopharyngitis	254 (7.0)	132 (6.1)
diarrhea	119 (3.3)	65 (3.0)
cough	76 (2.1)	30 (1.4)

The incidence of other adverse reactions when lidagliptin 5mg was compared with placebo when combined with a specific hypoglycemic agent: Uriton infection (3.1% vs. 0%) when combined with lidagliptin and sulfonylurea ) And hypertriglyceridemia (2.4% vs. 0%); hyperlipidemia (2.7% vs. 0.8%) and weight gain (2.3% vs. 0.8%) combined with lidagliptin and pioglitazone; Constipation when combined with basal insulin therapy (2.1% vs. 1%).

In a controlled study comparing rigagliptin with glimepiride, all patients received metformin at the same time. After 104 weeks of treatment, patients who were treated with ligagliptin (n = 776) reported The incidence of 5% and higher than those receiving sulfonylureas (n = 775) included back pain (9.1% vs. 8.4%), arthralgia (8.1% vs. 6.1%), upper respiratory infections (8.0%) (7.6%), headache (6.4% vs. 5.2%), cough (6.1% vs. 4.9%), and limb pain (5.3% vs. 3.9%).

Other adverse reactions reported in clinical studies receiving Ligliptin include hypersensitivity reactions (such as urticaria, angioedema, local skin exfoliation or bronchial hypersensitivity reactions) and myalgia. In clinical trials, 15.2 cases of pancreatitis were reported per 10,000 patient-years of exposure to patients treated with lidagliptin, compared to each of those receiving control treatment (placebo and the active control sulfonylurea). There were 3.7 reports of 10,000 patient-years exposed. After the last dose of ligagliptin, three additional cases of pancreatitis were reported.

Hypoglycemia

In a placebo-controlled study, 199 (6.6%) of 2994 patients treated with 5 mg of lidagliptin reported hypoglycemia, compared with 56 of 1546 placebo-treated patients (3.6 %)report. The incidence of hypoglycemia was similar to that of placebo when treated with lidagliptin monotherapy or in combination with metformin or pioglitazone. When Ligliptin was administered in combination with metformin and sulfonylurea, hypoglycemia was reported in 181 (22.9%) of 792 patients, compared with 39 of 263 patients receiving placebo in combination with metformin and sulfonylurea. People (14.8%) reported. The summary hypoglycemic adverse reaction is based on all reported hypoglycemia, and it is not necessary to obtain blood glucose measurements at the same time, or that some patients may have normal blood glucose levels. It is therefore not certain that all of these reported events reflect true hypoglycemic events.

In studies where lidagliptin was combined with a stable dose of insulin for up to 52 weeks (n = 1261), in terms of investigator-reported hypoglycemia events (defined as all symptomatic or asymptomatic self-measured blood glucose 70 mg / dL event), there was no significant difference between the lidagliptin group (31.4%) and the placebo group (32.9%). During the same period, severe hypoglycemia events (defined as requiring help from others and using carbohydrates, glucagon, or other resuscitation measures) were reported by 11 (1.7%) of patients treated with lidagliptin and receiving Seven (1.1%) of the placebo patients reported. Life-threatening or inpatient events were reported in 3 (0.5%) of patients treated with lidagliptin and 1 (0.2%) in patients receiving placebo.

Use in patients with renal insufficiency

In 133 patients with severe renal insufficiency (evaluated glomerular filtration rate (eGFR) value <30ml / min), the addition of ligagliptin or placebo to the original antidiabetic treatment for 52 weeks was compared. During the first 12 weeks of the study, background anti-diabetic treatments needed to be stable, including insulin, sulfonylureas, glitalins, and pioglitazone. For the remainder of the study, the dose of anti-diabetic background treatment was allowed to be adjusted.

In general, the incidence of adverse events, including severe hypoglycemia, is similar to the rates reported in other trials of lidagliptin. A higher incidence of hypoglycemia was observed due to the increased incidence of asymptomatic hypoglycemia events during the first 12 weeks of background hypoglycemic therapy stabilization (ligagliptin 63% compared to placebo 49%) .10 patients (15%) treated with lidagliptin and 11 patients (17%) received placebo reported at least one confirmed symptomatic hypoglycemia [with hand pointer blood glucose test value 54mg / dL ). During the same period, severe hypoglycemia events (defined as requiring help from others and taking carbohydrates, glucagon, or other resuscitation measures) were reported by 3 (4.4%) of patients treated with lidagliptin and receiving comfort 3 (4.6%) of patients receiving the drug were reported. Life-threatening or inpatient events were reported in 2 (2.9%) of patients treated with lidagliptin and 1 (1.5%) in patients receiving placebo.

Renal function, as measured by mean eGFR and creatinine clearance, did not change during the 52-week treatment period compared to the placebo group.

Laboratory inspection

Among patients receiving 5 mg of ligagliptin, laboratory findings were similar to those of patients receiving placebo. It was more common in the lidagliptin group, and its incidence exceeded laboratory changes of 1% in the placebo group, with an increase in uric acid (1.3% in the placebo group and 2.7% in the lidagliptin group).

No clinically significant changes in vital signs were observed in patients treated with lidagliptin.

Post-marketing experience

Other adverse reactions have been found during the application of Liglitinin tablets. Because these adverse reactions come from spontaneous reports from a population of uncertain size, it is often not possible to reliably estimate their frequency or establish a causal relationship with drug exposure.

l Acute pancreatitis, including fatal pancreatitis

l rash

Litagliptin taboos

It is contraindicated in patients with a history of allergies to ligagliptin, such as urticaria, angioedema, or bronchial hypersensitivity.

Ligliptin tablets precautions

General information

This product cannot be used to treat patients with type 1 diabetes, nor can it be used to treat diabetic ketoacidosis.

pancreatitis

Patients were informed that after the market for Ligliptin tablets, they have received post-marketing reports of acute pancreatitis, including fatal pancreatitis. Instruct patients to carefully observe the underlying symptoms and signs of pancreatitis. If there is persistent severe abdominal pain, sometimes it will be radiated to the back, with or without vomiting. This is a hallmark of acute pancreatitis. If pancreatitis is suspected, discontinue taking Ligliptin tablets and contact your doctor for appropriate measures. When patients with a history of pancreatitis take ligagliptin tablets, it is uncertain whether they increase the risk of pancreatitis.

In combination with drugs known to cause hypoglycemia

Insulin-promoting drugs and insulin are known to cause hypoglycemia. In a clinical trial, the combination of lidagliptin and insulinotropic drugs (for example, sulfonylureas) caused a lower incidence of hypoglycemia than placebo. Ligliptin combined with insulin can cause a higher incidence of hypoglycemia in patients with severe renal insufficiency. Therefore, when used in combination with lidagliptin, lower doses of insulin secretagogues or insulin are required to reduce the risk of hypoglycemia.

Large blood vessel results

There is no clear evidence that clinical studies have established that lidagliptin or other hypoglycemic drugs can reduce the risk of large blood vessels.

Impact on the ability to drive and operate machines

No research has been conducted on the effects on driving and machine operation capabilities. However, patients should be reminded of the risk of hypoglycemia, especially when used in combination with sulfonylureas.

Ligliptin tablets for pregnant and lactating women

Pregnancy

In rats and rabbits, reproduction studies were performed. However, adequate, well-controlled studies have not been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, this product should not be used during pregnancy unless really needed.

Ligliptin was administered to pregnant rats during the offspring organogenesis stage at a dose of 30 mg / kg and to pregnant rabbits at a dose of 150 mg / kg. It was not teratogenic. Based on the AUC exposure level, it was approximately 49 and 1943 at clinical doses. Times. In rats and rabbits, the dose of lidagliptin that caused maternal toxicity, in rats (1000 times the clinical dose), delayed development of skeletal ossification and a slight increase in rat embryo loss; in rabbits Medium (1943 times the clinical dose) will cause increased embryo absorption and visceral and skeletal changes.

Ligliptin is administered to female rats from the 6th day of pregnancy until the 21st day of lactation. At maternal toxic doses (exposure level> 1000 times the clinical dose), it causes weight loss and physical and behavioral development in male and female offspring. slow. Rat exposure levels were 49 times the clinical dose, and no functional, behavioral, or reproductive toxicity was observed in the offspring.

Ligliptin is administered orally and, in female rats and rabbits, can reach the fetus through the placenta.

Lactation

Existing animal data indicate that lidagliptin can be secreted into milk with a milk / plasma ratio of 4: 1. It is unclear whether the drug will be secreted into human milk. Because many drugs are secreted in human breast milk, care must be taken when breastfeeding women receive lidagliptin.

Ligliptin tablets for children

Data on the safety and effectiveness of this product in pediatric patients have not been established.

Ligliptin tablets for elderly

No dosage adjustment is needed for elderly patients.

In 15 clinical trials of Ligliptin, a total of 4040 patients with type 2 diabetes received 5 mg of Ligliptin: 1085 patients (27%) were 65 years of age or older and 131 patients (3%) were 75 years or older. Of these patients, 2566 participated in 12 double-blind placebo-controlled studies: 591 (23%) were 65 years or older, and 82 (3%) were 75 years or older. No differences in overall safety or effectiveness were found between patients 65 years and older and younger patients. Therefore, no dose adjustment is recommended for the elderly. Although no differences were found between elderly and young patients in the clinical studies of lidagliptin, the possibility that some older individuals would be more sensitive cannot be ruled out.

Ligliptin tablets drug interactions:

Pharmacokinetic interactions:
In vitro evaluation of drug interactions Ligliptin is a weak to moderate inhibitor of CYP isoenzyme CYP3A4, but it does not inhibit other CYP isoenzymes, nor is it an inducer of CYP isoenzymes, including: CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A11.
Ligliptin is a P-glycoprotein (P-gp) substrate that inhibits P-glycoprotein-mediated digoxin transport at high concentrations. Based on these results and in vivo drug interaction studies, it is considered that ligagliptin is unlikely to interact with other P-gp substrates at therapeutic concentrations.
In vivo evaluation of drug interactions with inducers of CYP3A4 or P-gp (eg, rifampicin) will reduce the exposure of rigagliptin to sub-therapeutic levels, likely to ineffective concentrations. For patients who need this type of drug, it is highly recommended to replace ligagliptin. In vivo studies have shown that drug interactions with CYP3A4, CYP2C9, CYP2C8, substrates of P-glycoproteins, and organic cation transporters (OCTs) are less likely to occur. Based on the results of the described pharmacokinetic studies, no dose adjustment recommendations for lidagliptin are available.

Ligliptin tablets overdose:

If Ligliptin overdose, go to the hospital immediately. Common support measures should also be taken based on the patient's clinical situation (for example, removal of unabsorbed drugs from the gastrointestinal tract, clinical monitoring, and supportive care). Ligliptin is unlikely to be cleared by hemodialysis or peritoneal dialysis.
In a controlled trial conducted in healthy subjects, a single dose of lidagliptin reached 600 mg (equivalent to 120 times the recommended daily dose), and there were no clinical adverse drug reactions related to the dose of the drug. There is no experience in humans using doses above 600 mg.

Clinical trials of Ligliptin tablets :

Studies have been conducted with lidagliptin monotherapy and combination therapy with metformin, glimepiride, pioglitazone, and insulin.
In a total of 10 double-blind, placebo-controlled clinical effectiveness studies evaluating the efficacy of lidagliptin in controlling blood glucose, a total of 3,648 patients with type 2 diabetes were randomized and received at least 12 weeks of lidagliptin exposure. In these studies, the overall ethnic / ethnic distribution was approximately 69% white, 29% Asian, and 2.5% black, including Hispanic / Latino 16%. 52% of patients are male. The overall mean age of the patients was 57 years (range 20-91 years). In addition, in 1551 patients with type 2 diabetes with poorly controlled metformin blood glucose, a 104-week controlled study of active drug (glimepiride) and 133 patients with severe chronic renal insufficiency (eGFR < 30ml / min) patients with type 2 diabetes conducted a 52-week placebo-controlled study.
In patients with type 2 diabetes, treatment with lidagliptin resulted in clinically significant improvements in glycated hemoglobin (HbA1c), fasting blood glucose (FPG), and 2-hour postprandial blood glucose (PPG) compared to placebo.
Combined therapy with metformin and a sulfonylurea (combined with metformin and sulfonylurea plus lidagliptin)
A total of 1,058 patients with type 2 diabetes participated in a 24-week randomized, double-blind, placebo-controlled study to evaluate the effectiveness of lidagliptin combined with a sulfonylurea and metformin. The most commonly used sulfonylureas in this study were: glimepiride (31%), glibenclamide (31%), and gliclazide (26%). Patients receiving sulfonylurea and metformin were randomized to receive either 5 or 5 mg of placebo, which were given once daily. Patients who fail to meet specific glycemic control goals during the study period will receive pioglitazone remedy. The measured blood glucose endpoints include HbA1c and FPG.
Compared with placebo, the combination of lidagliptin with a sulfonylurea and metformin resulted in statistically significant improvements in HbA1c and FPG (Table 4). In the entire study population (patients who received lidagliptin combined with sulfonylurea and metformin), the mean reduction in HbA1c relative to placebo was 0.6% from baseline and the FPG was reduced to 13 mg / dL. 5.4% of patients treated with 5 mg of ligagliptin and 13% of patients treated with placebo needed remedial treatment. There were no significant differences in body weight from baseline between the two groups.

Renal insufficiency < br A total of 133 patients with type 2 diabetes participated in a 52-week, double-blind, randomized, placebo-controlled study to evaluate ligagliptin in patients with both type 2 diabetes and severe chronic Effectiveness and safety in patients with renal insufficiency. Patients with estimated [based on MDRD formula] GFR values min are eligible to participate in the study. Based on baseline HbA1c values (8% or> 8%) and background anti-diabetic therapy (insulin or any combination therapy with insulin, sulfonylurea or glienat as monotherapy and pioglitazone or any other non-DPP-4 inhibition Agents of drugs) were stratified randomly. During the first 12 weeks of the study, background anti-diabetic treatments remained stable, including insulin, sulfonylureas, glitalides, and pioglitazone. For the remainder of the study, the dose of anti-diabetic background treatment was allowed to be adjusted. At baseline of the trial, 62.5% of patients received insulin alone as background diabetes treatment, and 12.5% of patients received sulfonylurea alone.
After 12 weeks of treatment, according to an analysis using the Last Observed-Forward (LOCF) analysis, Ligliptin 5mg had a statistically significant improvement in HbA1c compared to placebo, with a corrected mean change of -0.6 compared to placebo % (95% confidence interval is -0.9, -0.3). After the first 12 weeks, adjustments to the anti-diabetic background treatment were allowed for 52 weeks. Based on the analysis using LOCF, the mean change in baseline HbA1c from placebo compared to placebo was -0.7% (95% confidence interval is -1.0, -0.4).

Ligliptin tablets pharmacology and toxicology:

Pharmacological effects <br /> Ligliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor. DPP-4 can degrade insulinotropic hormone-like polypeptide-1 (GLP-1) and glucose-dependent insulinotropic peptides. (GIP). Litagliptin can increase the concentration of active enterotropic hormones, stimulate insulin release in a glucose-dependent manner, and reduce circulating glucagon levels.
Both of these enterotropic hormones are involved in the physiological regulation of glucose homeostasis. Intestinal insulin secretion is maintained at a low basal level throughout the day and rises immediately after meals. Under normal or elevated glucose levels, GLP-1 and GIP can increase pancreatic -cell insulin biosynthesis and secretion. In addition, GLP-1 can also reduce the glucagon secretion of pancreatic alpha cells, and reduce liver glucose excretion.
Pharmacodynamics <br /> Liglitin is capable of reversibly binding to DPP-4, thereby increasing the intestinal insulinotropic hormone concentration. Ligliptin promotes insulin secretion in a glucose-dependent manner, while reducing glucagon secretion, thereby better regulating the glucose balance in the body. In vitro, ligagliptin can selectively bind to DPP-4 and selectively inhibit DPP-4, but does not inhibit DPP-8 or DPP-9 activity at near therapeutic exposure levels.
Cardiac electrophysiology In a randomized, placebo-controlled, positive-control, 4-treatment-group crossover study, 36 healthy subjects received 5 mg of lidagliptin and 100 mg of lidagliptin (20 times the recommended dose), Moxifloxacin and placebo were administered. At the recommended dose of 5 mg or 100 mg, no increase in QTc was observed. At a 100 mg dose, the peak plasma concentration level of lidagliptin was approximately 38 times the peak concentration after the 5 mg dose was administered.
Toxicological studies <br Genetic toxicity<br /> The results of the Ames test, chromosomal aberration test of human lymphocytes, and micronucleus test in vivo were all negative.
Reproductive toxicity <br In the rat fertility and early embryonic developmental toxicity test, the doses of lidagliptin were 10, 30, and 240 mg / kg (the exposure was approximately 943 times the clinical dose of 5 mg / day). Early embryonic development, mating, fertility, and adverse effects of conception.
Carcinogenicity < br In a two-year carcinogenicity test in rats, the doses of lidagliptin were 6, 18, and 60 mg / kg (high-dose exposure was approximately 418 times the clinical dose), and no increase in tumor incidence was seen. In a two-year carcinogenicity test in mice, the doses of lidagliptin were 8, 25, and 80 mg / kg, and the doses of male and female animals were as high as 80 mg / kg or 25 mg / kg, respectively. (35, 270 times), there was no increase in tumor incidence, but the increase in lymphoma incidence was seen in female mice at a dose of 80 mg / kg (the exposure was approximately 215 times the clinical dose).

Pharmacokinetics of Ligliptin Tablets :

The characteristics of the pharmacokinetics of ligagliptin were studied in healthy subjects and two diabetic patients. After a single 5 mg oral dose in healthy subjects, peak plasma concentrations occurred approximately 1.5 hours (T _max ) after administration; the area under the average plasma curve (AUC) was 139 nmol · h / L, and the maximum plasma concentration (C _max ) was 8.9nmol / L.
The plasma concentration of lidagliptin is eliminated in at least two phases, and the terminal half-life is longer (> 100 hours), which is related to the saturable binding of lidagliptin to DPP-4. Longer half-life does not cause drug accumulation. After repeated oral administration of 5 mg dose of lidagliptin, it can be determined that the effective half-life of the accumulation of lidagliptin is about 12 hours. After once daily dosing, 5mg Ligliptin reached steady-state plasma concentration after the third dose, and the _Cmax and AUC reached at steady state increased by 1.3 compared with the first dose Times. The subject's own coefficient of variation and inter-subject coefficient of variation for both Ligliptin AUC were small (12.6% and 28.5%, respectively). In the dose range of 1 to 10 mg, the plasma AUC of lidagliptin increased in a manner below the dose ratio. The pharmacokinetics of lidagliptin in healthy subjects are usually similar to those in patients with type 2 diabetes.
The absolute bioavailability of risagliptin is about 30%. High-fat meals reduced C _max by 15% and increased AUC by 4%; this effect was not clinically relevant. Ligliptin can be taken with or without food.
Distribution The mean steady-state apparent volume of distribution of healthy subjects after a single intravenous injection of 5 mg of lidagliptin was approximately 1,110 liters, which indicates that lidagliptin is widely distributed in tissues. Ligliptin's plasma protein binding rate was concentration-dependent, and the plasma protein binding rate decreased from about 99% at 1 nmol / L to 75% ~ 89% at 30 nmol / L, which indicates that the binding of DPP-4 Saturation increases with increasing the concentration of ligagliptin. At high concentrations of fully saturated DPP-4, 70% to 80% of the Ligliptin is still bound to plasma proteins, so 30% to 20% of the Ligliptin in the plasma is unbound. Plasma binding was not affected in patients with renal or liver dysfunction.
After oral metabolism, most (approximately 90%) of Ligliptin is excreted as a prototype, suggesting that metabolism is a secondary elimination pathway. A small part of the absorbed risagliptin is metabolized to non-pharmacologically active metabolites, and its steady-state exposure level is 13.3% of ligagliptin.
Excretion <br After oral administration of [C] lipagliptin in healthy subjects, approximately 85% of the radioactivity was eliminated by the enterohepatic system (80%) or urine (5%) during the 4-day dosing period. Renal clearance at steady state is approximately 70 mL / min.
Pharmacokinetics in Specific Populations < br < br Kidney Insufficiency An open-label pharmacokinetic study was performed to evaluate the 5 mg dose of Ligliptin in men and women with varying degrees of chronic renal insufficiency. Pharmacokinetics in Female Patients. This study included 6 healthy subjects with normal renal function (creatinine clearance [CrCl] 80 ml / min) and 6 patients with mild renal insufficiency type 2 diabetes (CrCl: 50 to <80ml / min) , 6 patients with moderate renal insufficiency (30 to <50 ml / min), 10 patients with type 2 diabetes with severe renal insufficiency (<30 ml / min), and 11 patients with normal renal function. Creatinine clearance is measured by measuring the 24-hour urinary creatinine clearance, or estimated using serum creatinine according to the Cockcroft-Gault formula.
At steady state, the level of rigagliptin exposure in patients with mild renal insufficiency is comparable to healthy subjects.
In patients with moderate renal insufficiency, rigagliptin exposure was higher at steady state than in healthy subjects (AUC _{, ss} increased by 71%, C _max increased by 46%). The increase in exposure levels was not accompanied by an increase in the accumulation half-life, terminal half-life, or increase in the accumulation coefficient. Ritagliptin's renal excretion is less than 5% of the administered dose and is not affected by reduced renal function.
In patients with type 2 diabetes with severe renal insufficiency, steady-state exposure levels increased by approximately 40% compared with patients with type 2 diabetes with normal renal function (AUC _{, ss} increased by 42%, and Cmax increased by 35%). For both type 2 diabetes groups, renal excretion was less than 7% of the administered dose.
The results of population pharmacokinetic analysis further support these findings.
Hepatic Insufficiency In patients with mild hepatic insufficiency (Child-Pugh classification A), the steady-state exposure level (AUC _{, ss} ) of Ligliptin is approximately 25% lower than that of healthy subjects and Cmax is approximately 36%. In patients with moderate hepatic insufficiency (Child-Pugh classification B), the AUC _{, ss of} lidagliptin was about 14% lower than that of healthy subjects, and Cmax was about 8% lower. In patients with severe hepatic insufficiency (Child-Pugh classification C), the AUC _{, ss of} lidagliptin is comparable to healthy subjects, with Cmax approximately 23% lower. In patients with liver dysfunction, a decrease in pharmacokinetic parameters did not result in a decrease in inhibition.
Body mass index (BMI) / body weight need not be adjusted based on BMI / body weight. According to a population pharmacokinetic analysis, BMI / weight did not have a clinically significant effect on the pharmacokinetics of lidagliptin.
Gender need not be dose-adjusted based on gender. According to a population pharmacokinetic analysis, gender has no clinically significant effect on the pharmacokinetics of lidagliptin.
Elderly According to a population pharmacokinetic analysis, age has no clinically significant effect on the pharmacokinetics of ligagliptin.
Children have not studied the pharmacokinetics of ligagliptin in pediatric patients.
Race does not require dose adjustments based on race. Based on available pharmacokinetic data, race has no clinically significant effect on the pharmacokinetics of lidagliptin, including white, Hispanic, black and Asian patients.

Ligliptin Tablets Storage:

Store in a tightly closed container at a temperature not exceeding 25 ° C.
Keep out of reach of children.

Ligliptin Tablets Packaging:

Double aluminum blister pack.
7 pieces / box (1 plate × 7 pieces / board), 14 pieces / box (2 plates × 7 pieces / board), 28 pieces / box (4 plates × 7 pieces / board), 10 pieces / box (1 plate × 10 tablets / board), 30 tablets / box (3 plates × 10 tablets / board), 60 tablets / box (6 plates × 10 tablets / board).

The validity of Ligliptin tablets :

36 months

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