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 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.

• 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, PRIME-V study group
• Journal: Journal of diabetes investigation (J Diabetes Investig) Vol. 12 Issue 2 Pg. 200-206 (Feb 2021) ISSN: 2040-1124 [Electronic] Japan
• PMID: 32623839 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: © 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Chemical References

• Biomarkers
• Blood Glucose
• Glucosides
• Hypoglycemic Agents
• Sodium-Glucose Transporter 2 Inhibitors
• Thiophenes
• ipragliflozin
• Metformin
• Sitagliptin Phosphate

Topics

• Adult
• Aged
• Biomarkers (analysis)
• Blood Glucose (analysis)
• Bone and Bones (drug effects, pathology)
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Glucosides (therapeutic use)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Muscles (drug effects, pathology)
• Prognosis
• Prospective Studies
• Sitagliptin Phosphate (therapeutic use)
• Sodium-Glucose Transporter 2 Inhibitors (therapeutic use)
• Thiophenes (therapeutic use)
• Young Adult