Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes

Takahara, Mitsuyoshi; Shiraiwa, Toshihiko; Matsuoka, Taka-aki; Yamamoto, Kaoru; Maeno, Yoshifumi; Shiraiwa, Yuka; Yoshida, Yoko; Katakami, Naoto; Iijima, Hiroaki; Katsumata, Hideyuki; Arakawa, Kenji; Hashimoto, Toshio; Shimomura, Iichiro

doi:https://doi.org/10.2147/DMSO.S273396

Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes

Takahara, Mitsuyoshi; Shiraiwa, Toshihiko; Matsuoka, Taka-aki et al.

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2020, 13, 4457-4468

Number of Access:1,729（2025-07-18 10:00 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78261

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Title	Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes
Creator	NRID 1000000751067 1000000751067 researchmap permalink takahara-mitsuyoshi takahara-mitsuyoshi Scopus Author ID 35933605700 35933605700 CreatorName Takahara, Mitsuyoshi
	CreatorName Shiraiwa, Toshihiko
	NRID 1000010379258 1000010379258 CreatorName Matsuoka, Taka-aki
	CreatorName Yamamoto, Kaoru
	CreatorName Maeno, Yoshifumi
	CreatorName Shiraiwa, Yuka
	CreatorName Yoshida, Yoko
	NRID 1000010403049 1000010403049 researchmap permalink naoto.katakami naoto.katakami Scopus Author ID 7003392840 7003392840 CreatorName Katakami, Naoto
	CreatorName Iijima, Hiroaki
	CreatorName Katsumata, Hideyuki
	CreatorName Arakawa, Kenji
	CreatorName Hashimoto, Toshio
	NRID 1000060346145 1000060346145 researchmap permalink shimomura_i shimomura_i Scopus Author ID 7006715546 7006715546 ORCID 0000-0002-0851-9603 0000-0002-0851-9603 CreatorName Shimomura, Iichiro
Subject	Beta cell function
	Canagliflozin
	Glimepiride
	Glycemic control
	Type 2 diabetes mellitus
Description	This article is published in Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 18 November 2020, Volume 2020:13, Pages 4457-4468.
Abstract	Aim: Our aim was to investigate the effects of add-on canagliflozin with glimepiride dose adjustment or glimepiride dose adjustment on pancreatic beta cell function in patients with type 2 diabetes mellitus and inadequate glycemic control despite stable triple therapy (metformin, teneligliptin, and glimepiride) plus diet/exercise therapy. Methods: Forty patients on stable triple therapy were randomized to glimepiride dose adjustment without (glimepiride group) or with add-on canagliflozin 100 mg (canagliflozin group) for 24 weeks. The glimepiride dose was adjusted every 4 weeks based on continuous glucose monitoring over the previous 2 weeks according to a prespecified algorithm. After the 24-week treatment period, the patients returned to the pre-intervention regimen for 1 week (wash-out period). Patients underwent 75 g OGTTs at the start of the run-in period and at the end of the wash-out period. The primary endpoint was the change in disposition index (DI). Results: Thirty-nine patients completed the study (canagliflozin, n = 19; glimepiride, n = 20). The change in DI was +5.1% and −11.0% in the canagliflozin and glimepiride groups, respectively, with a between-group difference ratio of 18.0% (P = 0.330). HbA1c, fasting plasma glucose, body weight, and daily-life continuous glucose monitoring-derived para-meters improved in the canagliflozin group. Hypoglycemia occurred in 60% (44 episodes) and 70% (79 episodes) of patients in the canagliflozin and glimepiride groups, respectively. The change in DI was significantly correlated with the changes in glycemic control and variability in overall cohort. Conclusion: Adding canagliflozin to the triple therapy improved beta cell function by 18%, but it did not reach statistical significance. This study also demonstrated a correlation between the change in DI and glycemic control. As canagliflozin improved both glucose level and variability with relatively lower risk of hypoglycemia compared with glimepiride dose adjustment, adding canagliflozin to the triple therapy may be clinically beneficial.
Publisher	Dove Medical Press Ltd
Source Title	Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Volume (Issue)	13
Page	4457-4468
Date of Issued	2020-11-18
Language	English
Handle URL	https://hdl.handle.net/11094/78261
eISSN	11787007
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.2147/DMSO.S273396
Access Rights	open access
CopyRight
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020, 13, p. 4457-4468
DC.title	Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes
DC.creator	Takahara, Mitsuyoshi
	Shiraiwa, Toshihiko
	Matsuoka, Taka-aki
	Yamamoto, Kaoru
	Maeno, Yoshifumi
	Shiraiwa, Yuka
	Yoshida, Yoko
	Katakami, Naoto
	Iijima, Hiroaki
	Katsumata, Hideyuki
	Arakawa, Kenji
	Hashimoto, Toshio
	Shimomura, Iichiro
DC.publisher	Dove Medical Press Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-11-18
DC.identifier	https://doi.org/10.2147/DMSO.S273396
DC.subject	Beta cell function
	Canagliflozin
	Glimepiride
	Glycemic control
	Type 2 diabetes mellitus
DC.description	This article is published in Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 18 November 2020, Volume 2020:13, Pages 4457-4468.
DCTERMS.abstract	Aim: Our aim was to investigate the effects of add-on canagliflozin with glimepiride dose adjustment or glimepiride dose adjustment on pancreatic beta cell function in patients with type 2 diabetes mellitus and inadequate glycemic control despite stable triple therapy (metformin, teneligliptin, and glimepiride) plus diet/exercise therapy. Methods: Forty patients on stable triple therapy were randomized to glimepiride dose adjustment without (glimepiride group) or with add-on canagliflozin 100 mg (canagliflozin group) for 24 weeks. The glimepiride dose was adjusted every 4 weeks based on continuous glucose monitoring over the previous 2 weeks according to a prespecified algorithm. After the 24-week treatment period, the patients returned to the pre-intervention regimen for 1 week (wash-out period). Patients underwent 75 g OGTTs at the start of the run-in period and at the end of the wash-out period. The primary endpoint was the change in disposition index (DI). Results: Thirty-nine patients completed the study (canagliflozin, n = 19; glimepiride, n = 20). The change in DI was +5.1% and −11.0% in the canagliflozin and glimepiride groups, respectively, with a between-group difference ratio of 18.0% (P = 0.330). HbA1c, fasting plasma glucose, body weight, and daily-life continuous glucose monitoring-derived para-meters improved in the canagliflozin group. Hypoglycemia occurred in 60% (44 episodes) and 70% (79 episodes) of patients in the canagliflozin and glimepiride groups, respectively. The change in DI was significantly correlated with the changes in glycemic control and variability in overall cohort. Conclusion: Adding canagliflozin to the triple therapy improved beta cell function by 18%, but it did not reach statistical significance. This study also demonstrated a correlation between the change in DI and glycemic control. As canagliflozin improved both glucose level and variability with relatively lower risk of hypoglycemia compared with glimepiride dose adjustment, adding canagliflozin to the triple therapy may be clinically beneficial.
DC.rights
DC.format	78261
citation_title	Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes
citation_author	Takahara, Mitsuyoshi
	Shiraiwa, Toshihiko
	Matsuoka, Taka-aki
	Yamamoto, Kaoru
	Maeno, Yoshifumi
	Shiraiwa, Yuka
	Yoshida, Yoko
	Katakami, Naoto
	Iijima, Hiroaki
	Katsumata, Hideyuki
	Arakawa, Kenji
	Hashimoto, Toshio
	Shimomura, Iichiro
citation_publisher	Dove Medical Press Ltd
citation_language	English
citation_date	2020-11-18
citation_journal_title	Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
citation_volume	13
citation_firstpage	4457
citation_lastpage	4468
citation_doi	https://doi.org/10.2147/DMSO.S273396
citation_public_url	https://hdl.handle.net/11094/78261

Investigation of the effect of canagliflozin on the disposition index, a marker of pancreatic beta cell function, in patients with type 2 diabetes

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