A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. this column. For more information about call at 800-322-4349. The July 2013 monograph topics are prothrombin complex concentrate (human), cysteamine bitartrate delayed-release capsules, doxylamine succinate/pyridoxine hydrochloride, tedizolid phosphate, and sofosbuvir. The DUE/MUE is usually on canaglifozin. Indications Alogliptin is usually indicated for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It can be used as monotherapy or in combination with other antidiabetic medications, including metformin, sulfonylureas, thiazolidinediones, or insulin.1 Table 1 compares the US Food and Drug Administration (FDA)Capproved indications for dipeptidyl peptidase-4 (DPP-4) inhibitors. None of the brokers in this class should be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.1 Table 1. FDA-approved indications for DPP-4 inhibitors1,9,32,33 .05 for doses between 12.5 and 100 mg vs placebo). Secondary Endpoint(s): ? Least squares mean change in HbA1c from baseline to week 12 in the 113 patients not previously treated with antidiabetic therapy ranged from ?0.27% in the placebo group and ?0.65% in the alogliptin 6.25 mg group to ?0.92% with alogliptin 12.5 mg, ?0.85% with alogliptin 25 mg, ?0.72% with alogliptin 50 mg, and ?0.89% with alogliptin 100 mg ( .05 for 12.5, 25, and 100 mg doses vs placebo). ? The least squares mean change in fasting plasma glucose was +8.5 mg/dL in the placebo group, ?7.8 mg/dL in the 6.25 mg group, ?5.1 mg/dL in the 12.5 mg group, ?27 mg/dL in the 25 mg group, ?16.1 mg/dL in the 50 mg group, and ?20.9 mg/dL in the 100 mg group ( .05 for alogliptin 25 to 100 mg vs placebo). ? Weight changes were small in all groups (?0.5 to ?1.17 kg in the alogliptin groups and ?0.45 kg in the placebo group). ? The incidence of hypoglycemia also did not differ between groups. Comments: Dose-ranging study established efficacy with alogliptin doses from 12.5 to 100 mg. Reference: DeFronzo RA, et al, 20081,16 Study Design: Randomized, double-blind, multicenter study Study Funding: UPF-648 Takeda Patients: 329 patients with type 2 diabetes not adequately controlled with diet and exercise alone. The study population was 53% men and 67% White; the mean age was 53 years, and the mean baseline HbA1c was 7.9%. Intervention: Alogliptin 12.5 mg (133 patients), alogliptin 25 mg (131 patients), or placebo (65 patients) once daily for 26 weeks. Results: Primary Endpoint(s): ? Least squares mean change in HbA1c from baseline to week 26 in the ITT population: ?0.56% with alogliptin 12.5 mg and ?0.59% with alogliptin 25 mg compared with ?0.02% in the placebo group ( .001). Secondary Endpoint(s): ? HbA1c of 7% or less was achieved in 47.4% of patients in the alogliptin 12.5 mg group (= .001) and 44.3% in the alogliptin 25 mg group (= .008) compared with 23.4% of placebo recipients. ? Least squares mean change from baseline in fasting plasma glucose: ?10.3 mg/dL in the alogliptin 12.5 mg group and ?16.4 mg/dL in the alogliptin 25 mg group compared with an increase of 11.3 mg/dL in the placebo group ( .001). ? Changes in UPF-648 weight were comparable in the alogliptin (?0.09 and ?0.22 kg) and placebo (+0.18 kg) groups. ? The incidence of hypoglycemia also did not differ between groups (3% and 1.5% in the alogliptin groups vs 1.6% in the placebo group). Drug: Alogliptin vs Placebo or Metformin or Alogliptin plus Metformin Reference: package insert1 Study Design: Randomized, double-blind, multicenter study Study Funding: Takeda Patients: 784 patients inadequately controlled with diet and exercise; the mean baseline HbA1c was 8.4%. Intervention: Placebo, metformin 500 mg or 1,000 mg twice daily, alogliptin 12. 5 mg twice daily, alogliptin 25 mg once daily, or alogliptin 12. 5 mg plus metformin 500 or 1, 000 mg twice daily. Results: Primary Endpoint(s): ? Least squares mean change in HbA1c from baseline: 0.1% with placebo, ?0.6% with alogliptin 12.5 mg twice daily, ?0.7% with metformin 500 mg twice daily, ?1.1% with metformin 1,000 mg twice daily, ?1.2% with alogliptin 12.5 mg plus metformin 500 mg twice daily ( .05 vs alogliptin and metformin alone), and ?1.6% with alogliptin 12.5 mg plus metformin 1,000 mg twice daily ( .05 vs alogliptin and metformin alone). Secondary Endpoint(s): ? Patients achieving HbA1c less than 7%: 4% with placebo, 20% with alogliptin 12.5 mg twice daily, 27% with metformin 500 mg twice daily, 34% with metformin 1,000 mg twice daily, 47% with alogliptin 12.5 mg plus metformin 500 mg twice daily ( .05 vs alogliptin and metformin alone), and 59% with alogliptin 12.5 mg plus metformin 1,000 mg twice daily ( .05 vs alogliptin and metformin alone). ? Least squares mean change in fasting plasma glucose: 12 mg/dL with placebo, ?10 mg/dL with alogliptin 12.5 mg twice daily, ?12 mg/dL with metformin 500 mg twice daily,.The study population was about 50% men and 77% White; the mean age was 55 years, and the mean baseline HbA1c was 7.9%. Intervention: Alogliptin 12.5 mg (213 patients), alogliptin 25 mg (210 patients), or placebo (104 patients) once daily in addition to their ongoing metformin regimen (mean dosage, 1,837 to 1 1,868 mg/day) for 26 weeks. Results: Primary Endpoint(s): ? Least squares mean change in HbA1c from baseline to week 26 in the ITT population: ?0.6% in the alogliptin 12.5 mg group and ?0.6% in the alogliptin 25 mg group, compared with ?0.1% in the placebo group ( .001). Secondary Endpoint(s): ? HbA1c of 7% or less was achieved in 52% of patients in the alogliptin 12.5 mg group and 44% in the alogliptin 25 mg group compared with 18% of UPF-648 the placebo recipients ( .001). ? The least squares mean change from baseline in fasting plasma glucose was ?19 mg/dL in the alogliptin 12.5 mg group and ?17 mg/dL in the alogliptin 25 mg group compared with no change in the placebo group IL22RA1 ( .001). ? Incidence of fasting plasma glucose of 200 mg/dL or greater: 29% with alogliptin 12.5 mg ( .001) and 31% with alogliptin 25 mg (= .003) compared with 51% with placebo. ? Incidence of hyperglycemic rescue: 9% with alogliptin 12.5 mg (= .004) and 8% with alogliptin 25 mg (= .003) compared with 24% with placebo. ? Changes in weight were comparable in the alogliptin (?0.39 and ?0.67 kg) and placebo (?0.39 kg) groups. ? The incidence of hypoglycemia also did not differ between groups (0% to 1% in the alogliptin groups vs 3% in the placebo group); there were no reports of severe hypoglycemia in any of the groups. Comments: Alogliptin also demonstrated greater efficacy over 12 weeks than placebo in 288 Japanese patients with type 2 diabetes inadequately controlled with metformin plus diet and exercise when added to metformin.19 Drug: Alogliptin vs Pioglitazone vs Alogliptin plus Pioglitazone, as add-on therapy UPF-648 with Metformin Reference: DeFronzo RA, et al, 20121,20 Study Design: Randomized, double-blind, multicenter study Study Funding: Takeda Patients: 1,554 patients inadequately controlled on metformin (mean dosage, 1,887 mg/day). delayed-release capsules, doxylamine succinate/pyridoxine hydrochloride, tedizolid phosphate, and sofosbuvir. The DUE/MUE is usually on canaglifozin. Indications Alogliptin is usually indicated for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It can be used as monotherapy or in combination with other antidiabetic medications, including metformin, sulfonylureas, thiazolidinediones, or insulin.1 Table 1 compares the US Food and Drug Administration (FDA)Capproved indications for dipeptidyl peptidase-4 (DPP-4) inhibitors. None of the brokers in this class should be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.1 Table 1. FDA-approved indications for DPP-4 inhibitors1,9,32,33 .05 for doses between 12.5 and 100 mg vs placebo). Secondary Endpoint(s): ? Least squares mean change in HbA1c from baseline to week 12 in the 113 patients not previously treated with antidiabetic therapy ranged from ?0.27% in the placebo group and ?0.65% in the alogliptin 6.25 mg group to ?0.92% with alogliptin 12.5 mg, ?0.85% with alogliptin 25 mg, ?0.72% with alogliptin 50 mg, and ?0.89% with alogliptin 100 mg ( .05 for 12.5, 25, and 100 mg doses vs placebo). ? The least squares mean change in fasting plasma glucose was +8.5 mg/dL in the placebo group, ?7.8 mg/dL in the 6.25 mg group, ?5.1 mg/dL in the 12.5 mg group, ?27 mg/dL in the 25 mg group, ?16.1 mg/dL in the 50 mg group, and ?20.9 mg/dL in the 100 mg group ( .05 for alogliptin 25 to 100 mg vs placebo). ? Weight changes were small in all groups (?0.5 to ?1.17 kg in the alogliptin groups and ?0.45 kg in the placebo group). ? The incidence of hypoglycemia also did not differ between groups. Comments: Dose-ranging study established efficacy with alogliptin doses from 12.5 to 100 mg. Reference: DeFronzo RA, et al, 20081,16 Study Style: Randomized, double-blind, multicenter research Study Financing: Takeda Individuals: 329 individuals with type 2 diabetes not really adequately managed with exercise and diet alone. The analysis human population was 53% males and 67% White colored; the suggest age group was 53 years, as well as the suggest baseline HbA1c was 7.9%. Treatment: Alogliptin 12.5 mg (133 individuals), alogliptin 25 mg (131 individuals), or placebo (65 individuals) once daily for 26 weeks. Outcomes: Major Endpoint(s): ? Least squares mean modification in HbA1c from baseline UPF-648 to week 26 in the ITT human population: ?0.56% with alogliptin 12.5 mg and ?0.59% with alogliptin 25 mg weighed against ?0.02% in the placebo group ( .001). Supplementary Endpoint(s): ? HbA1c of 7% or much less was accomplished in 47.4% of individuals in the alogliptin 12.5 mg group (= .001) and 44.3% in the alogliptin 25 mg group (= .008) weighed against 23.4% of placebo recipients. ? Least squares mean differ from baseline in fasting plasma blood sugar: ?10.3 mg/dL in the alogliptin 12.5 mg group and ?16.4 mg/dL in the alogliptin 25 mg group weighed against a rise of 11.3 mg/dL in the placebo group ( .001). ? Adjustments in weight had been identical in the alogliptin (?0.09 and ?0.22 kg) and placebo (+0.18 kg) organizations. ? The occurrence of hypoglycemia also didn’t differ between organizations (3% and 1.5% in the alogliptin groups vs 1.6% in the placebo group). Medication: Alogliptin vs Placebo or Metformin or Alogliptin plus Metformin Research: package put in1 Study Style: Randomized, double-blind, multicenter research Study Financing: Takeda Individuals: 784 individuals inadequately managed with exercise and diet; the suggest baseline HbA1c was 8.4%. Treatment: Placebo, metformin 500 mg or 1,000 mg double daily, alogliptin 12.5 mg twice daily, alogliptin 25 mg once daily, or alogliptin 12.5 mg plus metformin 500 or 1,000 mg twice daily. Outcomes: Major Endpoint(s): ? Least squares mean modification in HbA1c from baseline: 0.1% with placebo, ?0.6% with alogliptin 12.5 mg twice daily, ?0.7% with metformin 500 mg twice daily, ?1.1% with metformin 1,000 mg twice daily, ?1.2% with alogliptin 12.5 mg plus metformin 500 mg twice daily ( .05 vs alogliptin and metformin alone), and ?1.6% with alogliptin 12.5 mg plus metformin 1,000 mg twice daily ( .05 vs alogliptin and metformin alone). Supplementary Endpoint(s): ? Patients attaining HbA1c significantly less than 7%: 4% with placebo, 20% with alogliptin 12.5 mg twice daily, 27% with metformin 500 mg twice daily, 34% with.