Shinya Nishio

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

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.

Flow Mediated Dilatation Is Reduced with the Progressive Stages of Glomerular Filtration Rate and Albuminuria in Type 2 Diabetic Patients without Coronary Heart Disease

We aimed to clarify the usefulness of measuring the flow mediated dilatation (FMD) in patients with type 2 diabetes mellitus without and with coronary heart disease (CHD). The FMD was measured in 480 patients with type 2 diabetes and in 240 nondiabetic subjects. The FMD was significantly lower in the subjects with CHD (n = 145, 5.4 ± 3.2%) than in those without CHD (n = 95, 6.9 ± 3.5%) among the nondiabetic subjects. The FMD was also lower in the subjects both with CHD (n = 161, 5.6 ± 2.8%) and without CHD (n = 319, 6.1 ± 3.3%) among the patients with diabetes compared to those without both diabetes and CHD. The FMD showed a significant positive correlation with the estimated glomerular filtration rate (eGFR) in the diabetic patients without CHD, while there was no significant association in those with CHD. The FMD was significantly lower with the progressive stages of the GFR or albuminuria in the patients without CHD among those with diabetes, although the FMD was not different in those with CHD. In conclusion, the FMD is considered to be useful for the detection of atherosclerosis in patients with type 2 diabetes, even if overt macroangiopathy is not diagnosed.

SGLT2 inhibitors in the pipeline for the treatment of diabetes mellitus in Japan

ABSTRACT Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors have been available for the treatment of type 2 diabetes (T2DM) in Japan since April 2014. The prescription rate in Japan is low in comparison to Western countries. We summarize the results obtained from the phase 3 clinical trials and clinical studies involving Japanese T2DM patients. We also discuss the current situation and the future prospects of SGLT2 inhibitors in Japan. Areas covered: Unexpected adverse events, such as cerebral infarction and diabetic ketoacidosis have been reported from clinics shortly after the initiation of SGLT2 inhibitor treatment. However, the reductions in blood glucose levels and body weight have been demonstrated in phase 3 trials using 6 types of SGLT2 inhibitors, while observational studies of Japanese T2DM patients, which were performed in the clinical setting, showed that the incidence of adverse drug reactions, such as severe hypoglycemia, was low. Expert opinion: SGLT2 inhibitors are also considered to be effective for treating Japanese patients with T2DM. When prescribing SGLT2 inhibitors, it is necessary to ensure that they are used appropriately because the Japanese T2DM patient population has a high proportion of elderly individuals and a high incidence of cerebrovascular disease.

Comparison of the antidiabetic effects of linagliptin among groups with a normal renal function and a mild or severe renal impairment – retrospective observation study of Japanese patients with type 2 diabetes mellitus

Objective: The clinical course > 6 months after the initiation of linagliptin in patients with type 2 diabetes was compared among the groups divided by their renal function. Methods: Two hundred and sixteen Japanese patients with type 2 diabetes treated with 5 mg once daily linagliptin were studied as the treated set. One hundred and forty-five subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into three groups based on an eGFR: eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m2. The parameters were analyzed separately in the patients receiving monotherapy and additional therapy of linagliptin. Results: The HbA1c (NGSP) levels significantly improved in both the patients receiving monotherapy and additional therapy. The changes in the HbA1c levels at 6 months were not significantly different between the groups with an eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m2 receiving monotherapy (−1.0, −0.8 and −0.8%, respectively). Similarly, those were not significantly different between the different groups receiving additional therapy (−0.6, −0.5 and −0.7%, respectively). Conclusions: Linagliptin is considered to be effective for patients with type 2 diabetes and renal impairment in the present analysis performed at our institution.

Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus

Background The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. Methods The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. Results The glycated hemoglobin (HbA1c) level (8.3%±1.8% to 8.2%±1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04). Conclusion B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.

The Ratio of Serum Eicosapentaenoic Acid to Arachidonic Acid Is Associated With Renal Impairment and Diabetic Macroangiopathies in Elderly Patients With Type 2 Diabetes

A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) has been reported to correlate with coronary heart disease (1–3), and no previous studies have investigated serum polyunsaturated fatty acid (PUFA) levels exclusively in patients with diabetes, in whom atherosclerotic diseases are commonly found. We therefore examined the association between serum EPA/AA ratio and the prevalence of diabetic angiopathies in patients with type 2 diabetes. The serum levels of EPA and AA were determined in 744 Japanese patients with type 2 diabetes (aged 67 ± 12 years, 60% males, duration of diabetes 13 ± 11 years, estimated glomerular filtration rate [eGFR] 78 ± 32 mL/min/1.73 m2, serum EPA 79.6 ± 52.6 μg/mL, serum AA 189.5 ± 55.0 μg/mL) and in 285 age- and sex-matched subjects without diabetes between October and December 2012. …