Journal Article

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)

Ishikawa, Ko, Hashimoto, Naotake, Shoji, Mayumi, Hattori, Akiko, Ohara, Emi, Baba, Yusuke, Sakamoto, Kenichi, Shimofusa, Ryouta, Kobayashi, Akina, Sato, Yasunori, Yokoh, Hidetaka, Ogino, Jun, Ishibashi, Ryoichi, Takahashi, Sho, Koshizaka, Masaya, Onishi, Shunichiro, Ide, Shintaro, Horikoshi, Takuro, Yamaga, Masaya, Ishikawa, Takahiro, Maezawa, Yoshiro, Newby, L. Kristin, Ide, Kana, Tokuyama, Hirotake, Nagashima, Kengo, Shimada, Fumio, Kitamoto, Takumi, Takemoto, Minoru, Yokote, Koutaro, Nakamura, Susumu, Uchida, Daigaku, Kobayashi, Kazuki

2021

Overview

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. Ipragliflozin in combination with sitagliptin did not affect bones or muscles adversely compared to metformin. However, ipragliflozin increased the levels of the bone resorption marker, tartrate‐resistant acid phosphatase 5b.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Acid phosphatase (tartrate-resistant) / Acids / Adult / Aged / Antidiabetics / Biomarkers - analysis / Blood Glucose - analysis / Body mass index / Bone and Bones - drug effects / Bone and Bones - pathology / Bone density / Bone growth / Bone metabolism / Bone resorption / Clinical Trial / Clinical trials / Confidence intervals / Congestive heart failure / Cross-Sectional Studies / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - drug therapy / Drug Therapy, Combination / Female / Follow-Up Studies / Fractures / Glucose / Glucosides - therapeutic use / Hemoglobin / Humans / Hypoglycemic Agents - therapeutic use / Male / Metabolism / Metformin / Metformin - therapeutic use / Middle Aged / Muscles - drug effects / Muscles - pathology / Osteogenesis / Patients / Phosphatase / Prognosis / Prospective Studies / Renal failure / Sitagliptin Phosphate - therapeutic use / Sodium / Sodium-glucose cotransporter / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Sodium–glucose cotransporter 2 inhibitor / Thiophenes - therapeutic use / Vertebrae / Young Adult