trelagliptin and alogliptin

Observational studies and meta-analyses of randomized trials on dipeptidyl peptidase-4 inhibitors (DPP4i) reported discordant results on the risk of malignancies with this class of drugs. Aim of the present meta-analysis is the assessment of the effect of DPP4i treatment on the incidence of different types of cancer, collecting all available evidence from randomized controlled trials.. An extensive MEDLINE, EMBASE, and Cochrane database search for sitagliptin or vildagliptin or omarigliptin or saxagliptin or alogliptin or trelagliptin or anagliptin or linagliptin or gemigliptin or evogliptin or teneligliptin was performed up to September 30th, 2019. All trials performed on type 2 diabetes, with duration ≥ 24 weeks, and comparing of DPP4i with placebo or active drugs were collected. The study has been registered on PROSPERO (#153344). Mantel-Haenszel odds ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes.. A total of 157 eligible trials were identified. DPP-4i were not associated with an increased risk of overall cancer (MH-OR 0.93 [0.86, 1.00]; p = 0.07), with no significant differences across individual molecules of the class. When compared with placebo/none, a lower risk of cancer with DPP-4i was observed in placebo-controlled trials (MH-OR 0.90 [0.82, 0.99], p = 0.030), whereas no significant differences have been detected with any other comparators. DPP-4i was associated with a significant reduction in colorectal cancer (MH-OR 0.70 [0.53, 0.94], p = 0.020).. Available data do not support the hypothesis of an association of DPP4i treatment with malignancies, with a possible beneficial effect for colon-rectal cancer.

Topics: Adamantane; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Humans; Incidence; Neoplasms; Piperidines; Randomized Controlled Trials as Topic; Risk Factors; Sitagliptin Phosphate; Uracil; Vildagliptin

Dipeptidyl peptidase-4 (DPP-4) inhibitors are weight neutral and well tolerated, and provide better glycaemic control for a longer period compared to conventional therapies. Despite the fact that various drugs are available, glycaemic control remains suboptimal in approximately half of patients with type 2 diabetes mellitus; one of the major reasons for low medication adherence.. A novel DPP-4 inhibitor, trelagliptin, was approved in Japan in March 2015, and is the first once-weekly oral antidiabetic agent in the world. In this review, current issues concerning medication adherence for the treatment of diabetes are discussed followed by a summary of the characteristics and future expectations of trelagliptin, by reviewing the recent phase I, II, and III clinical studies of trelagliptin.. Trelagliptin has demonstrated superiority to placebo and non-inferiority to alogliptin, indicating its efficacy and tolerance in Japanese patients. Trelagliptin is expected to improve adherence and prevent complications. Due to the convenient dosing regimen, it is expected to be widely used in the clinical setting. A large-scale long-term study will help further confirm its long-term efficacy and safety, patients' satisfaction, and medication adherence.

Topics: Asian People; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Japan; Piperidines; Uracil

This open-label, parallel-group, exploratory study examined the effects of two dipeptidyl peptidase 4 (DPP4) inhibitors on glycemic variability (GV) in patients with type 2 diabetes.. Randomized patients with glycated hemoglobin A1c of at least 6.5% to less than 8.5% received trelagliptin 100 mg (n = 13) once weekly or alogliptin 25 mg (n = 14) once daily for 29 days. Continuous glucose monitoring was performed before the start of the treatment period (baseline) and from day 21 to 29, inclusive. The primary endpoint was change from baseline in the standard deviation (SD) of 24-h blood glucose values, measured daily for 7 days (day 22-28) of the treatment period. Secondary and additional efficacy endpoints included changes in glycemic parameters and the rate of DPP4 inhibition, respectively. Adverse events (AEs) were monitored to assess safety.. Mean change from baseline in the SD of 24-h blood glucose (95% confidence interval) at day 28 was - 7.35 (- 15.13, 0.44) for trelagliptin and - 11.63 (- 18.67, - 4.59) for alogliptin. In both treatment groups, glycemic parameters improved and the rate of DPP4 inhibition was maintained. Three patients reported AEs; no severe treatment-emergent AEs were reported in either group.. Once-weekly trelagliptin and once-daily alogliptin improved glycemic control and reduced GV without inducing hypoglycemia.. ClinicalTrials.gov (NCT02771093) and JAPIC (JapicCTI-163250).. Takeda Pharmaceutical Company, Ltd.

Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Pilot Projects; Piperidines; Uracil

Topics: Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Patient Preference; Physician-Patient Relations; Piperidines; Practice Patterns, Physicians'; Surveys and Questionnaires; Uracil

Trelagliptin is a novel once-weekly oral DPP-4 inhibitor. We assessed the efficacy and safety of trelagliptin versus the daily oral DPP-4 inhibitor alogliptin in Japanese patients with type 2 diabetes.. We did a randomised, double-blind, active-controlled, parallel-group, phase 3, non-inferiority study at 26 sites in Japan. We included individuals with type 2 diabetes inadequately controlled by diet and exercise. We randomly assigned patients (2:2:1) to receive trelagliptin (100 mg) once per week, alogliptin (25 mg) once per day, or placebo for 24 weeks. Randomisation was done electronically and independently from the study with permuted blocks of ten patients. Patients and clinicians were masked to group assignment. Patients in the trelagliptin group were given trelagliptin once a week and oral alogliptin placebo every day, whereas patients in the alogliptin group were given oral trelagliptin placebo once a week and oral alogliptin every day (double-dummy design). Patients in the placebo group were given an oral alogliptin placebo once a day and an oral trelagliptin placebo once a week. Our primary outcome was between-groups difference in change in HbA1c concentration from baseline to the end of treatment. The non-inferiority margin was 0·4%. Our analysis included all patients who were randomised and received at least one dose of study drug. The study is registered with ClinicalTrials.gov, number NCT01632007.. Between May 26, 2012, and Nov 20, 2012, we enrolled 357 patients. 243 patients were included in the analysis (101 for trelagliptin, 92 for alogliptin, and 50 for placebo). In the primary analysis, the least squares mean change in HbA1c concentration was -0·33% in the trelagliptin group (SE 0·059) and -0·45% in the alogliptin group (0·061) based on the ANCOVA model. The least squares mean difference (trelagliptin minus alogliptin) of change from baseline in HbA1c concentration was 0·11% (95% CI -0·054 to 0·281). Trelagliptin was non-inferior to alogliptin. Both active groups had significantly reduced mean HbA1c concentrations at end of treatment compared with placebo (p<0·0001). The frequency of adverse events was similar between groups. No hypoglycaemia was reported with trelagliptin and the drug was well tolerated.. The once-weekly DPP-4 inhibitor trelagliptin showed similar efficacy and safety to alogliptin once daily in Japanese patients with type 2 diabetes. Trelagliptin could be a useful new antidiabetes drug that needs to be given once a week.. Takeda Pharmaceutical Company.

Topics: Administration, Oral; Asian People; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Glycated Hemoglobin; Humans; Piperidines; Uracil

Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro properties of trelagliptin, which exhibited approximately 4- and 12-fold more potent inhibition against human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and >10,000-fold selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9. Kinetic analysis revealed reversible, competitive and slow-binding inhibition of dipeptidyl peptidase-4 by trelagliptin (t1/2 for dissociation ≈ 30 minutes). X-ray diffraction data indicated a non-covalent interaction between dipeptidyl peptidase and trelagliptin. Taken together, potent dipeptidyl peptidase inhibition may partially contribute to sustained efficacy of trelagliptin.

Topics: Animals; Crystallography, X-Ray; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Dogs; Humans; Male; Piperidines; Rats, Sprague-Dawley; Sitagliptin Phosphate; Substrate Specificity; Time Factors; Uracil