Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus

Aim: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. Materials and methods: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. Results: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were −1.09% ± 0.85% and −0.88% ± 0.86% for HbA1c, −1.40% ± 2.54% and −2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. Conclusions: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients

上肢の関節可動域が制限される人のためのエプロン提案 : 着脱動作分析による検証

加齢や障がいにより関節可動域が狭くなると、後ろで紐を結ぶタイプのエプロンは着用が困難となる。本研究では、上肢の動きを制限された人でも簡単に着脱できるエプロンを提案し、着脱時の負担を軽減できるかどうかを検証するため、着脱時の関節の動き、筋肉への負担を一般的なエプロンと比較した。紐を後ろで結ぶ一般的なタイプの「レギュラーエプロン」と市販のエプロンホルダーを使用したワンタッチで着脱できる金城学院ファッション工房の「オリジナルエプロン」を同じ布地で製作した。健康な女子大学生10名を被験者とし、上肢4か所と僧帽筋の筋電図を記録し、筋電積分値から着脱時の筋肉への負荷量を比較した。被験者の前方・右側面の2 方向から着脱動作を撮影し、各ポイント（手首、肘、肩）の上下・左右・前後方向の動きを解析した。着脱時間は、オリジナルエプロンの方がかなり短かった。オリジナルエプロンの筋電積分値は、レギュラーエプロンの10～20％であった。手首の動きをみると、レギュラーエプロンでは、前方と後方だけでなく、上方にも大きく動いているが、オリジナルエプロンでは上下移動はほとんどなく、わずかに後方へ動いているだけであった。各部位の最大移動距離を比較すると、いずれの部位でもレギュラーエプロンの方が有意に大きかった。以上より、オリジナルエプロンは、レギュラーエプロンに比べて小さな動きで、短時間で着脱することができ、筋肉への負担も小さいことが確かめられた

Efficacy and safety of canagliflozin in combination with insulin: A double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus

Background: Combination therapy with canagliflozin and insulin was investigated in a prescribed substudy of the canagliflozin Cardiovascular Assessment Study (CANVAS); however, it was not evaluated in Japanese patients with type 2 diabetes mellitus (T2DM). Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients, we determined the clinical benefit of such a combination therapy in Japanese patients. Methods: Patients who had inadequate glycemic control despite insulin, diet and exercise therapies were randomized into placebo (n = 70) and canagliflozin 100 mg (n = 76) groups that were administered once daily in addition to their prior insulin therapy in this double-blind, placebo-controlled study. The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from the baseline to week 16. Results: There was a statistically significant decrease in HbA1c levels from the baseline in the canagliflozin group ( 0.97 ± 0.08 %) compared with the placebo group (0.13 ± 0.08 %) at week 16 [last observation carried forward (LOCF)]. The decrease in HbA1c levels in the canagliflozin group was independent of the insulin regimen (premixed, long-acting and long-acting plus rapid- or short-acting). Compared with the placebo group, canagliflozin significantly decreased fasting plasma glucose levels (-34.1 ± 4.8 vs -1.4 ± 5.0 mg/dL) and body weights (-2.13 ± 0.25 vs 0.24 ± 0.26 %), and significantly increased HDL cholesterol (3.3 ± 1.0 vs -0.5 ± 1.0 mg/dL) and HOMA2- %B (10.15 ± 1.37 vs 0.88 ± 1.42 %). The overall incidence of adverse events was similar between the two groups. The incidence and incidence per subject-year exposure of hypoglycemia (hypoglycemic symptoms and/or decreased blood glucose) were slightly higher in the canagliflozin group (40.0 % and 7.97) than in the placebo group (29.6 % and 4.51). However, hypoglycemic events in both groups were mild in severity and dose-reduction of insulin by <10 % from the baseline following hypoglycemic events decreased the incidence per subject-year exposure in the canagliflozin group. The incidence of hypoglycemia between the groups did not differ according to the insulin regimen. Conclusion: Canagliflozin in combination with insulin was effective in improving glycemic control and reducing body weight and well tolerated by Japanese patients with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT0222092

Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin

Sodium glucose co‐transporter 2 (SGLT2) inhibitors have been associated with increased serum ketone body levels in patients with type 2 diabetes mellitus (T2DM). In the present analysis we evaluated serum ketone body levels and variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2‐fold were seen with both canagliflozin doses. The median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for β‐hydroxybutyrate. Approximately two‐thirds of the variability in each ketone measure was attributed to intra‐subject variability. Intra‐subject variability was higher for serum ketones than other metabolites. Patients in the lowest response tertile exhibited no increase in ketones. Those in the highest response tertile tended to be male and have higher fasting plasma glucose levels, lower insulin levels, and longer T2DM duration at baseline. Moreover, changes in serum ketones were not fully explained by changes in plasma fatty acids, suggesting downstream effects of SGLT2 inhibition on hepatic metabolism that favour ketogenesis. In summary, increases in serum ketone bodies with canagliflozin were greater and more variable than changes in other metabolic measures in Japanese patients with T2DM