Efficacy and Safety of Alogliptin in Patients With Type 2 Diabetes: Analysis of the ATTAK-J Study

Abstract

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to reduce hemoglobin A1c (HbA1c) in patients with type 2 diabetes, but the reduction varies between patients and adequate glycemic control may not be achieved. We evaluated the efficacy and safety of the DPP-4 inhibitor alogliptin in the real clinical setting, and analyzed factors associated with the improvement of HbA1c by alogliptin treatment.MethodsA retrospective observational study was performed in patients with type 2 diabetes attending hospitals or clinics belonging to the Kanagawa Physicians Association who received treatment with alogliptin for 1 year or longer. Patients using insulin were excluded from the study. The efficacy endpoints were HbA1c (National Glycohemoglobin Standardization Program value), blood glucose (fasting/postprandial), body weight, blood pressure (systolic/diastolic), liver function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and γ-glutamyl transpeptidase), kidney function (serum creatinine and estimated glomerular filtration rate), serum lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), and serum amylase. Adverse events were compiled to assess safety.ResultsOf 330 patients whose case records were collected, 27 patients were excluded for protocol violations, leaving 303 patients to form the full analysis set. Compared with baseline, HbA1c showed a decrease by 0.54±1.22% (mean ± standard deviation) after 12 months of alogliptin treatment. Factor analysis demonstrated that the change of HbA1c after 12 months was significantly influenced by the baseline HbA1c level, duration of diabetes, concomitant use of sulfonylureas, and compliance with diet therapy. In addition, there was a significant reduction of total cholesterol, low-density lipoprotein cholesterol, and the estimated glomerular filtration rate after 12 months of alogliptin treatment, as well as a significant increase in serum creatinine. No significant changes of body weight, blood pressure, or liver function were observed. Symptoms of hypoglycemia occurred in two patients (0.6%).ConclusionsAlogliptin displayed a significant hypoglycemic effect and excellent safety in routine clinical use. Factors influencing the change of HbA1c with alogliptin therapy may include the HbA1c at the start of treatment, the duration of diabetes, use of sulfonylureas, and compliance with diet therapy.

Comparative effect of dipeptidyl-peptidase 4 inhibitors on laboratory parameters in patients with diabetes mellitus

“…Kubota et al reported that administration of sitagliptin significantly decreased TC and LDL concentrations, and tended to decrease HDL concentration in patients with type 2 DM, up to 12 weeks [9]. Takeda et al reported that administration of alogliptin significantly decreased TC and LDL concentrations in patient with type 2 DM, up to 12 weeks [20]. In our results, HDL concentration was slightly decreased in the exposure period in sitagliptin and vildagliptin users.…”

Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims-based cohort study

“…As illustrated in the current study, DPP-4i is widely used in Japan, and this concurs with findings from other studies. For example, the ATTAK-J study reported real-world evidence of significant hypoglycaemic activity and favourable safety for DPP-4i therapy in Japanese patients with T2DM 25. The PREFERENCE 4 study documented that treatment-naive Japanese patients preferred (in terms of treatment satisfaction) a DPP-4i to a BG, SU, or α-GI 26.…”

“…As approximately 60% of such patients are treatment-naïve, DPP-4i is establishing a definitive role in the first-line treatment of T2DM in Japan 1 31. Although no significant association between DPP-4i and possible pancreatic disorder was observed in several large-scale studies,25 32–34 it is important to remain vigilant for potential safety signals35 since DPP-4i-related pancreatitis is a low but established risk 36…”

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

“…These findings have resulted in eight commercially available DPP-IV inhibitors, including alogliptin (Nesina ® , Vipidia ® ; Keating, 2015;Takeda et al, 2016), anagliptin , gemigliptin (Zemiglo ® ; Kim et al, 2013;Jung et al, 2014), linagliptin (Forst and Pfutzner, 2012;Barnett, 2015), saxagliptin Anderson et al, 2016), sitagliptin (Januvia ® , Xelevia ® , Glactiv ® , Tesavel ® ; Garg et al, 2013;Plosker, 2014), teneligliptin (Nakamaru et al, 2015), and vildagliptin (Galvus ® , Novartis AG; Mikhail, 2008;Richter et al, 2008), being approved and entering into the clinic . These DPP-IV inhibitors have good oral bioavailability and a relatively long duration of action in patients with T2DM.…”