Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

Abstract

Aim: This study aims to assess the association between sodium–glucose cotransporter type-2 inhibitor (SGLT-2i) treatment and muscle atrophy in patients with type 2 diabetes mellitus (T2DM). Methods: We searched six databases from 1 January 2012 to 1 May 2023, without language restrictions. The primary outcome was muscle. Secondary outcomes were weight loss, weakness, malaise, or fatigue. Subgroup analyses were performed according to different definitions of muscle, treatment duration, and measurement methods. The quality of the studies was assessed using the Cochrane tool. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Results: Nineteen randomized controlled trials (RCTs) involving 1,482 participants were included. Compared with the control group, a meta-analysis showed that T2DM participants in the group treated with SGLT-2i demonstrated statistically significant reductions in lean body mass of 0.66 (95% confidence interval (CI), −1.05 to −0.27; p = 0.0009) and skeletal muscle mass of 0.35 (95% CI, −0.66 to −0.04; p = 0.03). No deaths or serious adverse events were reported. The quality of evidence in the included trials was low. Conclusions: SGLT-2i may lead to a reduction in muscle strength in the treatment of T2DM compared to the control group. However, there is still a lack of high-quality evidence to evaluate muscle atrophy caused by SGLT-2i. Systematic review registration: https://inplasy.com/inplasy-2022-12-0061/, identifier 2022120061.