{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:54:20Z","timestamp":1792086860539,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Recent randomized clinical trials have suggested that sodium\u2013glucose cotransporter\u00a02 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium\u2013glucose cotransporter\u00a02 inhibitors on bone and muscle are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A subanalysis of a randomized controlled study was carried out to evaluate the effects of the sodium\u2013glucose cotransporter\u00a02 inhibitor, ipragliflozin, versus metformin on bone and muscle in Japanese patients with type\u00a02 diabetes mellitus (baseline body mass index \u226522\u00a0kg\/m<jats:sup>2<\/jats:sup> and hemoglobin A1c 7\u201310%) who were already receiving sitagliptin. These patients were randomly administered ipragliflozin 50\u00a0mg or metformin 1,000\u20131,500\u00a0mg daily. The effects of these medications on the bone formation marker, bone alkali phosphatase; the bone resorption marker, tartrate\u2010resistant acid phosphatase\u00a05b (TRACP\u20105b); handgrip strength; abdominal cross\u2010sectional muscle area; and bone density of the fourth lumbar vertebra were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After 24\u00a0weeks of treatment, the changes in bone density of the fourth lumbar vertebra, handgrip strength and abdominal cross\u2010sectional muscle area were not significantly different between the two groups. However, TRACP\u20105b levels increased in patients treated with ipragliflozin compared with patients treated with metformin (median 11.94 vs \u221210.30%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), showing that ipragliflozin can promote bone resorption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u20105b. A long\u2010term study is required to further understand the effects of this TRACP\u20105b increase caused by ipragliflozin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13340","type":"journal-article","created":{"date-parts":[[2020,7,5]],"date-time":"2020-07-05T04:00:25Z","timestamp":1593921625000},"page":"200-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type\u00a02 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME\u2010V study)"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-9993","authenticated-orcid":false,"given":"Masaya","family":"Koshizaka","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Diabetes, Metabolism and Endocrinology Chiba University Hospital Chiba 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