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Cardiovasc Diabetol. 2016 Jun 18;15:89. doi: 10.1186/s12933-016-0407-4.

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

Author information

1
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
2
Clinical Research Department II, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
3
Data Science Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
4
Medical Science Center, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
5
Medical Science Center, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan. Iijima.Hiroaki@mm.mt-pharma.co.jp.

Abstract

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: NCT02220920.

KEYWORDS:

Canagliflozin; Combination therapy; Insulin; Japanese patients; SGLT2 inhibitor; Type 2 diabetes mellitus

PMID:
27316668
PMCID:
PMC4912792
DOI:
10.1186/s12933-016-0407-4
[Indexed for MEDLINE]
Free PMC Article

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