Side Effects, Interactions, Warning, Dosage & Uses. CLINICAL PHARMACOLOGYMechanism Of Action. TRULICITY contains dulaglutide, which is a human GLP- 1 receptor agonist with 9. GLP- 1 (7- 3. 7). Dulaglutide activates the GLP- 1 receptor, a membrane- bound cell- surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (c. AMP) in beta cells leading to glucose- dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying. Pharmacodynamics. TRULICITY lowers fasting glucose and reduces postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus. The reduction in fasting and postprandial glucose can be observed after a single dose. Fasting And Postprandial Glucose. In a clinical pharmacology study in adults with type 2 diabetes mellitus, treatment with once weekly TRULICITY resulted in a reduction of fasting and 2- hour PPG concentrations, and postprandial serum glucose incremental AUC, when compared to placebo (- 2. L,- 5. 9. 5 mg/d. L, and - 1. 97 mg h/d. L, respectively); these effects were sustained after 6 weeks of dosing with the 1. First- And Second- Phase Insulin Secretion. Both first- and second- phase insulin secretion were increased in patients with type 2 diabetes treated with TRULICITY compared with placebo. Insulin And Glucagon Secretion. TRULICITY stimulates glucose- dependent insulin secretion and reduces glucagon secretion. Treatment with TRULICITY 0. Week 2. 6 by 3. 5. L, respectively, and C- peptide concentration by 0. L, respectively, in a Phase 3 monotherapy study. In the same study, fasting glucagon concentration was reduced by 1. L from baseline with TRULICITY 0. Gastric Motility. Dulaglutide causes a delay of gastric emptying. Tabtight professional, free when you need it, VPN service. Téléchargements - Wii Info, tout pour Hacker la Wii, les tutoriaux et les news du Hack Wii. Jogos da Dora : Vestir-se e administra o trem expresso como navegador Nick Jr. The delay is largest after the first dose and diminishes with subsequent doses. Cardiac Electrophysiology (QTc)The effect of dulaglutide on cardiac repolarization was tested in a thorough QTc study. Dulaglutide did not produce QTc prolongation at supratherapeutic doses of 4 and 7 mg. Pharmacokinetics. The pharmacokinetics of dulaglutide is similar between healthy subjects and patients with type 2 diabetes mellitus. Following subcutaneous administration, the time to maximum plasma concentration of dulaglutide at steady- state ranges from 2. After multiple- dose administration of 1. Cmax) and total systemic exposure (AUC) of dulaglutide were 1. L (range 5. 6 to 2. L) and 1. 4,0. 00 ng*h/m. L (range 6. 94. 0 to 2. L), respectively; accumulation ratio was approximately 1. Steady- state plasma dulaglutide concentrations were achieved between 2 and 4 weeks following once weekly administration. Site of subcutaneous administration (abdomen, upper arm, and thigh) had no statistically significant effect on the exposure to dulaglutide. Absorption. The mean absolute bioavailability of dulaglutide following subcutaneous administration of single 0. Distribution . The mean volumes of distribution after subcutaneous administration of TRULICITY 0. L (range 1. 4. 3 to 2. L) and 1. 7. 4 L (range 9. L), respectively. Metabolism . Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways. Elimination. The mean apparent clearance at steady state of dulaglutide is approximately 0. L/h for the 0. 7. L/h for the 1. 5 mg dose. The elimination half- life of dulaglutide for both doses is approximately 5 days. Specific Populations. No dose adjustment of dulaglutide is needed based on age, gender, race, ethnicity, body weight, or renal or hepatic impairment. The effects of intrinsic factors on the PK of dulaglutide are shown in Figure 1. Figure 1: Impact of intrinsic factors on dulaglutide pharmacokinetics. Renal. Dulaglutide systemic exposure was increased by 2. ESRD renal impairment sub- groups, respectively, compared to subjects with normal renal function. The corresponding values for increase in Cmax were 1. Figure 1). In clinical pharmacology studies, dulaglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Pharmacokinetic (PK) measures indicating the magnitude of these interactions are presented in Figure 2. No dose adjustment is recommended for any of the evaluated co- administered medications. Figure 2: Impact of dulaglutide on the pharmacokinetics of co- administered medications. Potential For Co- Administered Drugs To Influence The Pharmacokinetics Of Dulaglutide. In a clinical pharmacology study, the coadministration of a single dose of dulaglutide (1. AUC and Cmax of approximately 3. Animal Toxicology And/Or Pharmacology. Zucker diabetic fatty (ZDF) rats were given 0. MRHD based on AUC) for 3 months. Increases of 1. 2% to 3. Other changes in the dulaglutide- treated animals included increased interlobular ductal epithelium without active ductal cell proliferation (. In 4 of 1. 9 monkeys on dulaglutide treatment, there was an increase in goblet cells within the pancreatic ducts, but no differences from the control group in total amylase or lipase at study termination. There were no proliferative changes in the thyroid C- cells. Clinical Studies. TRULICITY has been studied as monotherapy and in combination with metformin, sulfonylurea, metformin and sulfonylurea, metformin and thiazolidinedione, basal insulin with or without metformin, and prandial insulin with or without metformin. The studies evaluated the use of TRULICITY 0. Dexmedetomidine is an Uptitration was not performed in any of the trials; patients were initiated and maintained on either 0. In patients with type 2 diabetes mellitus, TRULICITY produced reductions from baseline in Hb. A1c compared to placebo. No overall differences in glycemic effectiveness were observed across demographic subgroups (age, gender, race/ethnicity, duration of diabetes). Monotherapy. In a 5. TRULICITY 0. 7. 5 mg once weekly, TRULICITY 1. Seventy- five percent (7. Most patients previously treated with an antidiabetic agent were receiving metformin (~9. Patients had a mean age of 5. Forty- four percent were male. The White, Black and Asian race accounted for 7. Twenty- nine percent of the study population were from the US. Treatment with TRULICITY 0. Hb. A1c from baseline at the 2. Table 3). The difference in observed effect size between TRULICITY 0. Table 3: Results at Week 2. Trial of TRULICITY as Monotherapya 2. Week Primary Time Point. TRULICITY 0. 7. 5 mg. TRULICITY 1. 5 mg. Metformin 1. 50. 0- 2. Intent- to- Treat (ITT) Population (N). Last observation carried forward (LOCF) was used to impute missing data. Data post- onset of rescue therapy are treated as missing. At Week 2. 6, primary efficacy was missing for 1. TRULICITY 0. 7. 5 mg, TRULICITY 1. Least- squares mean adjusted for baseline value and other stratification factors. The primary analysis included 2. Combination Therapy. Add- On To Metformin. In this 1. 04- week placebo- controlled, double- blind study (5. TRULICITY 0. 7. 5 mg once weekly, TRULICITY 1. Randomization occurred after an 1. Patients had a mean age of 5. White, Black and Asian were 5. US. At the 2. 6 week placebo- controlled time point, the Hb. A1c change was 0. TRULICITY 0. 7. 5 mg, TRULICITY 1. The percentage of patients who achieved Hb. A1c < 7. 0% was 2. TRULICITY 0. 7. 5 mg, TRULICITY 1. At 2. 6 weeks, there was a mean weight reduction of 1. TRULICITY 0. 7. 5 mg, TRULICITY 1. There was a mean reduction of fasting glucose of 9 mg/d. L, 3. 5 mg/d. L, 4. L, and 1. 8 mg/d. L for placebo, TRULICITY 0. TRULICITY 1. 5 mg, and sitagliptin, respectively. Treatment with TRULICITY 0. Hb. A1c compared to placebo (at 2. Table 4 and Figure 3). Table 4: Results at Week 5. TRULICITY Compared to Sitagliptin used as Add- On to Metformina 5. Week Primary Time Point. TRULICITY 0. 7. 5 mg. TRULICITY 1. 5 mg. Sitagliptin 1. 00 mg. Intent- to- Treat (ITT) Population (N). Last observation carried forward (LOCF) was used to impute missing data. At Week 5. 2 primary efficacy was missing for 1. TRULICITY 0. 7. 5 mg, TRULICITY 1. Daily. Med - TRULICITY- dulaglutide injection, solution. TRULICITY has been studied as monotherapy and in combination with metformin, sulfonylurea, metformin and sulfonylurea, metformin and thiazolidinedione, basal insulin with or without metformin, and prandial insulin with or without metformin. The studies evaluated the use of TRULICITY 0. Uptitration was not performed in any of the trials; patients were initiated and maintained on either 0. In patients with type 2 diabetes mellitus, TRULICITY produced reductions from baseline in Hb. A1c compared to placebo. No overall differences in glycemic effectiveness were observed across demographic subgroups (age, gender, race/ethnicity, duration of diabetes). Monotherapy In a 5. TRULICITY 0. 7. 5 mg once weekly, TRULICITY 1. Seventy- five percent (7. Most patients previously treated with an antidiabetic agent were receiving metformin (~9. Patients had a mean age of 5. Forty- four percent were male. The White, Black and Asian race accounted for 7. Twenty- nine percent of the study population were from the US. Treatment with TRULICITY 0. Hb. A1c from baseline at the 2. Table 3). The difference in observed effect size between TRULICITY 0. Combination Therapy Add- on to Metformin. In this 1. 04- week placebo- controlled, double- blind study (5. TRULICITY 0. 7. 5 mg once weekly, TRULICITY 1. Randomization occurred after an 1. Patients had a mean age of 5. White, Black and Asian were 5. US. At the 2. 6 week placebo- controlled time point, the Hb. A1c change was 0. TRULICITY 0. 7. 5 mg, TRULICITY 1. The percentage of patients who achieved Hb. A1c < 7. 0% was 2. TRULICITY 0. 7. 5 mg, TRULICITY 1. At 2. 6 weeks, there was a mean weight reduction of 1. TRULICITY 0. 7. 5 mg, TRULICITY 1. There was a mean reduction of fasting glucose of 9 mg/d. L, 3. 5 mg/d. L, 4. L, and 1. 8 mg/d. L for placebo, TRULICITY 0. TRULICITY 1. 5 mg, and sitagliptin, respectively. Treatment with TRULICITY 0. Hb. A1c compared to placebo (at 2. Table 4 and Figure 3). Figure 3: Adjusted Mean Hb. A1c Change at each Time Point (ITT, MMRM) and at Week 5. ITT, LOCF)Add- on to Sulfonylurea. In this 2. 4- week placebo- controlled, double- blind study, 2. TRULICITY 1. 5 mg, both as add- on to glimepiride. Patients had a mean age of 5. White, Black, and Asian were 8. US. At 2. 4 weeks, treatment with once weekly TRULICITY 1. Hb. A1c compared to placebo (Table 5). Add- on to Metformin and Thiazolidinedione. In this 5. 2- week placebo- controlled study (2. TRULICITY 0. 7. 5 mg once weekly, TRULICITY 1. BID, all as add- on to maximally tolerated doses of metformin (. Exenatide treatment group assignment was open- label while the treatment assignments to placebo, TRULICITY 0. TRULICITY 1. 5 mg were blinded. After 2. 6 weeks, patients in the placebo treatment group were randomized to either TRULICITY 0. TRULICITY 1. 5 mg once weekly to maintain study blind. Randomization occurred after a 1. Patients randomized to exenatide started at a dose of 5 mcg BID for 4 weeks and then were escalated to 1. BID. Patients had a mean age of 5. White, Black and Asian were 7. US. Treatment with TRULICITY 0. Hb. A1c compared to placebo (at 2. Table 6 and Figure 4). Over the 5. 2- week study period, the percentage of patients who required glycemic rescue was 8. TRULICITY 0. 7. 5 mg once weekly + metformin and pioglitazone treatment group, 3. TRULICITY 1. 5 mg once weekly + metformin and pioglitazone treatment group, and 8. BID + metformin and pioglitazone treatment group. Figure 4: Adjusted Mean Hb. A1c Change at Each Time Point (ITT, MMRM) and at Week 2. ITT, LOCF) Add- on to Metformin and Sulfonylurea. In this 7. 8- week (5. TRULICITY dose assignment), 8. TRULICITY 0. 7. 5 mg once weekly, TRULICITY 1. Randomization occurred after a 1. This was followed by a 6- to 8- week glycemic stabilization period prior to randomization. Insulin glargine dose adjustments occurred twice weekly for the first 4 weeks of treatment based on self- measured fasting plasma glucose (FPG), followed by once weekly titration through Week 8 of study treatment, utilizing an algorithm that targeted a fasting plasma glucose of < 1. L. Only 2. 4% of patients were titrated to goal at the 5. The dose of glimepiride could be reduced or discontinued after randomization (at the discretion of the investigator) in the event of persistent hypoglycemia. The dose of glimepiride was reduced or discontinued in 2. TRULICITY 0. 7. 5 mg, TRULICITY 1. Patients had a mean age of 5. White, Black and Asian were 7. US. Treatment with TRULICITY once weekly resulted in a reduction in Hb. A1c from baseline at 5. Table 7). The difference in observed effect size between TRULICITY 0. Combination Therapy with Basal Insulin, with or without Metformin. In this 2. 8- week placebo- controlled, double- blind study, 3. TRULICITY 1. 5 mg, as add- on to titrated basal insulin glargine (with or without metformin). Patients had a mean age of 6. White, Black, and Asian were 9. US. The mean starting dose of insulin glargine was 3. TRULICITY 1. 5 mg. At randomization, the initial insulin glargine dose in patients with Hb. A1c < 8. 0% was reduced by 2. At 2. 8 weeks, treatment with once weekly TRULICITY 1. Hb. A1c compared to placebo (Table 8). Combination Therapy with Prandial Insulin, with or without Metformin In this 5. TRULICITY dose assignment), 8. Randomization occurred after a 9- week lead- in period; during the initial 2 weeks of the lead- in period, patients continued their pre- study insulin regimen but could be initiated and/or up- titrated on metformin, based on investigator discretion; this was followed by a 7- week glycemic stabilization period prior to randomization. At randomization, patients discontinued their pre- study insulin regimen and were randomized to TRULICITY 0. TRULICITY 1. 5 mg once weekly, or insulin glargine once daily, all in combination with prandial insulin lispro 3 times daily, with or without metformin. Insulin lispro was titrated in each arm based on preprandial and bedtime glucose, and insulin glargine was titrated to a fasting plasma glucose goal of < 1. L. Only 3. 6% of patients randomized to glargine were titrated to the fasting glucose goal at the 2. Patients had a mean age of 5. White, Black and Asian were 7. US. Treatment with TRULICITY 0. Hb. A1c from baseline. The difference in observed effect size between TRULICITY 0.
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