Anagliptin in the treatment of type 2 diabetes: safety, efficacy, and patient acceptability

Abstract

Anagliptin is a novel dipeptidyl peptidase-4 inhibitor that has been available in Japan since 2012. Because anagliptin is not generally used in countries other than Japan, there are only a small number of reports investigating the effects of anagliptin. In the present article, we review the safety and efficacy of anagliptin according to data obtained from preclinical trials and postmarketing studies. The usual dose of anagliptin is 200 mg daily, and increases in the dose up to 400 mg daily have been approved in cases in which the blood glucose-lowering effect is insufficient. In a Phase II trial, the reduction in the HbA1c values from baseline after 12 weeks monotherapy with 200 mg and 400 mg of daily anagliptin was 0.75%±0.50% and 0.82%±0.46%, respectively, and more than 40% of the subjects receiving anagliptin at a dose of 200 mg or 400 mg daily achieved an HbA1c level below 6.9%. Furthermore, the levels of HbA1c, fasting blood glucose, and postprandial blood glucose were significantly decreased at 52 weeks compared with the baseline values in a Phase III trial investigating the effects of anagliptin included in combination therapy with other oral antidiabetic agents. In a pooled analysis of Phase II and Phase II/III trials, the goal achievement rates for an HbA1c level below 7.0% at 12 weeks were 40.3%, 39.4%, 30.0%, and 34.8% in the patients treated with anagliptin combined with α-glucosidase inhibitors, thiazolidinediones, sulfonylureas, and biguanides, respectively. Meanwhile, the serum lipid concentrations significantly improved after the administration of anagliptin in a pooled analysis of Phase III trials, and no serious adverse effects have been reported in preclinical trials. Therefore, the use of anagliptin in patients with type 2 diabetes is considered to be safe and effective for both monotherapy and combination therapy.

Keywords: adverse effect; combination therapy; dipeptidyl peptidase-4 inhibitor; monotherapy; type 2 diabetes mellitus.

Figure 1

Prescription rates of antidiabetic agents. Notes: The data were obtained from the database of Edogawa Hospital over three months. The prescription rate was calculated as the number of patients prescribed each class of antidiabetic agent divided by the total number of patients prescribed any type of antidiabetic agent. The number of patients prescribed α-glucosidase inhibitors, sulfonylureas, thiazolidinediones, and glinides has declined continuously since the release of dipeptidyl peptidase-4 (DPP-4) inhibitors. The rate of prescription of dipeptidyl peptidase-4 inhibitors increased steadily to more than 50% in 2013. In contrast, the use of insulin and biguanides has remained relatively stable at approximately 30%. Copyright ©2013. Journal of Japan Diabetes Society. Adapted from Ando S, Tsugami E, Suzuki S, et al. Recent trend in the prescription rates of antidiabetic agents in our facility. Journal of Japan Diabetes Society. 2013; 56 Suppl 1: S164. Abbreviations: DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1.

Figure 2

Data for (A) patient age, (B) estimated glomerular filtration rate (eGFR), (C) urinary C-peptide, and (D) therapeutic methods for type 2 diabetes among the groups divided according to the duration of illness. Notes: A population of 1,436 patients diagnosed with type 2 diabetes mellitus whose duration of illness was described in their medical records and who were treated for more than 6 months at the Department of Diabetes, Metabolism and Kidney Disease of Edogawa Hospital between 2008 and 2011 was examined. While the patient ages significantly increased in association with a longer duration of illness (P<0.0001, analysis of variance), both the estimated glomerular filtration rate (n=1436) and urinary C-peptide (n=424) values were significantly reduced (P<0.0001, analysis of variance). The proportion of patients receiving insulin treatment increased in association with a longer duration of illness (P<0.0001, χ² test). The data are shown as the means ± standard deviation. Filled, hatched, and open bars indicate insulin (including the combination of insulin and oral antidiabetic agents), oral antidiabetic agents, and nonpharmacological therapies, respectively.