Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)

Abstract Aims/Introduction Recent randomized clinical trials have suggested that sodium–glucose cotransporter 2 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium–glucose cotransporter 2 inhibit...

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Main Authors: Masaya Koshizaka, Ko Ishikawa, Ryoichi Ishibashi, Yoshiro Maezawa, Kenichi Sakamoto, Daigaku Uchida, Susumu Nakamura, Masaya Yamaga, Hidetaka Yokoh, Akina Kobayashi, Shunichiro Onishi, Kazuki Kobayashi, Jun Ogino, Naotake Hashimoto, Hirotake Tokuyama, Fumio Shimada, Emi Ohara, Takahiro Ishikawa, Mayumi Shoji, Shintaro Ide, Kana Ide, Yusuke Baba, Akiko Hattori, Takumi Kitamoto, Takuro Horikoshi, Ryouta Shimofusa, Sho Takahashi, Kengo Nagashima, Yasunori Sato, Minoru Takemoto, L. Kristin Newby, Koutaro Yokote, the PRIME‐V study group
Format: Article
Language:English
Published: Wiley 2021-02-01
Series:Journal of Diabetes Investigation
Subjects:
Online Access:https://doi.org/10.1111/jdi.13340
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author Masaya Koshizaka
Ko Ishikawa
Ryoichi Ishibashi
Yoshiro Maezawa
Kenichi Sakamoto
Daigaku Uchida
Susumu Nakamura
Masaya Yamaga
Hidetaka Yokoh
Akina Kobayashi
Shunichiro Onishi
Kazuki Kobayashi
Jun Ogino
Naotake Hashimoto
Hirotake Tokuyama
Fumio Shimada
Emi Ohara
Takahiro Ishikawa
Mayumi Shoji
Shintaro Ide
Kana Ide
Yusuke Baba
Akiko Hattori
Takumi Kitamoto
Takuro Horikoshi
Ryouta Shimofusa
Sho Takahashi
Kengo Nagashima
Yasunori Sato
Minoru Takemoto
L. Kristin Newby
Koutaro Yokote
the PRIME‐V study group
author_facet Masaya Koshizaka
Ko Ishikawa
Ryoichi Ishibashi
Yoshiro Maezawa
Kenichi Sakamoto
Daigaku Uchida
Susumu Nakamura
Masaya Yamaga
Hidetaka Yokoh
Akina Kobayashi
Shunichiro Onishi
Kazuki Kobayashi
Jun Ogino
Naotake Hashimoto
Hirotake Tokuyama
Fumio Shimada
Emi Ohara
Takahiro Ishikawa
Mayumi Shoji
Shintaro Ide
Kana Ide
Yusuke Baba
Akiko Hattori
Takumi Kitamoto
Takuro Horikoshi
Ryouta Shimofusa
Sho Takahashi
Kengo Nagashima
Yasunori Sato
Minoru Takemoto
L. Kristin Newby
Koutaro Yokote
the PRIME‐V study group
author_sort Masaya Koshizaka
collection DOAJ
description Abstract Aims/Introduction Recent randomized clinical trials have suggested that sodium–glucose cotransporter 2 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium–glucose cotransporter 2 inhibitors on bone and muscle are unclear. Materials and Methods A subanalysis of a randomized controlled study was carried out to evaluate the effects of the sodium–glucose cotransporter 2 inhibitor, ipragliflozin, versus metformin on bone and muscle in Japanese patients with type 2 diabetes mellitus (baseline body mass index ≥22 kg/m2 and hemoglobin A1c 7–10%) who were already receiving sitagliptin. These patients were randomly administered ipragliflozin 50 mg or metformin 1,000–1,500 mg daily. The effects of these medications on the bone formation marker, bone alkali phosphatase; the bone resorption marker, tartrate‐resistant acid phosphatase 5b (TRACP‐5b); handgrip strength; abdominal cross‐sectional muscle area; and bone density of the fourth lumbar vertebra were evaluated. Results After 24 weeks of treatment, the changes in bone density of the fourth lumbar vertebra, handgrip strength and abdominal cross‐sectional muscle area were not significantly different between the two groups. However, TRACP‐5b levels increased in patients treated with ipragliflozin compared with patients treated with metformin (median 11.94 vs −10.30%, P < 0.0001), showing that ipragliflozin can promote bone resorption. Conclusions There were no adverse effects on bone or muscle when sitagliptin was used in combination with either ipragliflozin or metformin. However, ipragliflozin combination increased the levels of TRACP‐5b. A long‐term study is required to further understand the effects of this TRACP‐5b increase caused by ipragliflozin.
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spelling doaj.art-a5bbfb0922504f7fa64e1190a5344a692022-12-21T21:34:38ZengWileyJournal of Diabetes Investigation2040-11162040-11242021-02-0112220020610.1111/jdi.13340Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)Masaya Koshizaka0Ko Ishikawa1Ryoichi Ishibashi2Yoshiro Maezawa3Kenichi Sakamoto4Daigaku Uchida5Susumu Nakamura6Masaya Yamaga7Hidetaka Yokoh8Akina Kobayashi9Shunichiro Onishi10Kazuki Kobayashi11Jun Ogino12Naotake Hashimoto13Hirotake Tokuyama14Fumio Shimada15Emi Ohara16Takahiro Ishikawa17Mayumi Shoji18Shintaro Ide19Kana Ide20Yusuke Baba21Akiko Hattori22Takumi Kitamoto23Takuro Horikoshi24Ryouta Shimofusa25Sho Takahashi26Kengo Nagashima27Yasunori Sato28Minoru Takemoto29L. Kristin Newby30Koutaro Yokote31the PRIME‐V study groupDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Endocrinology, Hematology, and Gerontology Chiba University Graduate School of Medicine Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Endocrinology, Hematology, and Gerontology Chiba University Graduate School of Medicine Chiba JapanHotaruno Central Naika Kisarazu JapanOdayama Clinic Kisarazu JapanDepartment of Diabetes and Metabolism Japanese Red Cross Narita Hospital Narita JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Diabetes and Metabolism Asahi General Hospital Asahi JapanDepartment of Endocrinology, Hematology, and Gerontology Chiba University Graduate School of Medicine Chiba JapanDepartment of Diabetes, Endocrine and Metabolic Disease Tokyo Women's Medical University Yachiyo Medical Center Yachiyo JapanDepartment of Diabetes, Endocrine and Metabolic Disease Tokyo Women's Medical University Yachiyo Medical Center Yachiyo JapanYukarigaoka Tokuyama Medical Clinic Sakura JapanDepartment of Diabetes and Metabolism National Hospital Organization Chiba Medical Center Chiba JapanDepartment of Diabetes and Metabolism National Hospital Organization Chiba Medical Center Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanDiagnostic Radiology and Radiation Oncology Chiba University Graduate School of Medicine Chiba JapanDepartment of Radiology Sannou Hospital Chiba JapanClinical Research Support Center The Jikei University School of Medicine Tokyo JapanResearch Center for Medical and Health Data Science The Institute of Statistical Mathematics Tachikawa JapanDepartment of Preventive Medicine and Public Health Keio University School of Medicine Shinjuku‐ku JapanDepartment of Medicine Division of Diabetes, Metabolism and Endocrinology International University of Health and Welfare Narita JapanDuke Clinical Research Institute Duke University Medical Center Durham North Carolina USADepartment of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba JapanAbstract Aims/Introduction Recent randomized clinical trials have suggested that sodium–glucose cotransporter 2 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium–glucose cotransporter 2 inhibitors on bone and muscle are unclear. Materials and Methods A subanalysis of a randomized controlled study was carried out to evaluate the effects of the sodium–glucose cotransporter 2 inhibitor, ipragliflozin, versus metformin on bone and muscle in Japanese patients with type 2 diabetes mellitus (baseline body mass index ≥22 kg/m2 and hemoglobin A1c 7–10%) who were already receiving sitagliptin. These patients were randomly administered ipragliflozin 50 mg or metformin 1,000–1,500 mg daily. The effects of these medications on the bone formation marker, bone alkali phosphatase; the bone resorption marker, tartrate‐resistant acid phosphatase 5b (TRACP‐5b); handgrip strength; abdominal cross‐sectional muscle area; and bone density of the fourth lumbar vertebra were evaluated. Results After 24 weeks of treatment, the changes in bone density of the fourth lumbar vertebra, handgrip strength and abdominal cross‐sectional muscle area were not significantly different between the two groups. However, TRACP‐5b levels increased in patients treated with ipragliflozin compared with patients treated with metformin (median 11.94 vs −10.30%, P < 0.0001), showing that ipragliflozin can promote bone resorption. Conclusions There were no adverse effects on bone or muscle when sitagliptin was used in combination with either ipragliflozin or metformin. However, ipragliflozin combination increased the levels of TRACP‐5b. A long‐term study is required to further understand the effects of this TRACP‐5b increase caused by ipragliflozin.https://doi.org/10.1111/jdi.13340Bone metabolismMetforminSodium–glucose cotransporter 2 inhibitor
spellingShingle Masaya Koshizaka
Ko Ishikawa
Ryoichi Ishibashi
Yoshiro Maezawa
Kenichi Sakamoto
Daigaku Uchida
Susumu Nakamura
Masaya Yamaga
Hidetaka Yokoh
Akina Kobayashi
Shunichiro Onishi
Kazuki Kobayashi
Jun Ogino
Naotake Hashimoto
Hirotake Tokuyama
Fumio Shimada
Emi Ohara
Takahiro Ishikawa
Mayumi Shoji
Shintaro Ide
Kana Ide
Yusuke Baba
Akiko Hattori
Takumi Kitamoto
Takuro Horikoshi
Ryouta Shimofusa
Sho Takahashi
Kengo Nagashima
Yasunori Sato
Minoru Takemoto
L. Kristin Newby
Koutaro Yokote
the PRIME‐V study group
Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)
Journal of Diabetes Investigation
Bone metabolism
Metformin
Sodium–glucose cotransporter 2 inhibitor
title Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)
title_full Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)
title_fullStr Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)
title_full_unstemmed Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)
title_short Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME‐V study)
title_sort effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in japanese patients with type 2 diabetes mellitus subanalysis of a prospective randomized controlled study prime v study
topic Bone metabolism
Metformin
Sodium–glucose cotransporter 2 inhibitor
url https://doi.org/10.1111/jdi.13340
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