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).
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.
Koshizaka, M; Ishikawa, K; Ishibashi, R; Maezawa, Y; Sakamoto, K; Uchida, D; Nakamura, S; Yamaga, M; Yokoh, H; Kobayashi, A; Onishi, S; Kobayashi, K; Ogino, J; Hashimoto, N; Tokuyama, H; Shimada, F; Ohara, E; Ishikawa, T; Shoji, M; Ide, S; Ide, K; Baba, Y; Hattori, A; Kitamoto, T; Horikoshi, T; Shimofusa, R; Takahashi, S; Nagashima, K; Sato, Y; Takemoto, M; Newby, LK; Yokote, K; PRIME-V study group,
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)