TY - JOUR
T1 - Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus
T2 - Subanalysis of a prospective, randomized, controlled study (PRIME-V study)
AU - Koshizaka, Masaya
AU - Ishikawa, Ko
AU - Ishibashi, Ryoichi
AU - Maezawa, Yoshiro
AU - Sakamoto, Kenichi
AU - Uchida, Daigaku
AU - Nakamura, Susumu
AU - Yamaga, Masaya
AU - Yokoh, Hidetaka
AU - Kobayashi, Akina
AU - Onishi, Shunichiro
AU - Kobayashi, Kazuki
AU - Ogino, Jun
AU - Hashimoto, Naotake
AU - Tokuyama, Hirotake
AU - Shimada, Fumio
AU - Ohara, Emi
AU - Ishikawa, Takahiro
AU - Shoji, Mayumi
AU - Ide, Shintaro
AU - Ide, Kana
AU - Baba, Yusuke
AU - Hattori, Akiko
AU - Kitamoto, Takumi
AU - Horikoshi, Takuro
AU - Shimofusa, Ryouta
AU - Takahashi, Sho
AU - Nagashima, Kengo
AU - Sato, Yasunori
AU - Takemoto, Minoru
AU - Newby, L. Kristin
AU - Yokote, Koutaro
N1 - Funding Information:
KY received research grants from Astellas Pharma Inc. and MSD K.K. (Tokyo, Japan). He also received a lecture fee from Astellas Pharma Inc. and Sumitomo Dainippon Pharma (Tokyo, Japan). The other authors declare no conflict of interest.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Bone metabolism
KW - Metformin
KW - Sodium–glucose cotransporter 2 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85089661199&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089661199&partnerID=8YFLogxK
U2 - 10.1111/jdi.13340
DO - 10.1111/jdi.13340
M3 - Article
C2 - 32623839
AN - SCOPUS:85089661199
JO - Journal of Diabetes Investigation
JF - Journal of Diabetes Investigation
SN - 2040-1116
ER -