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

Abstract

AimThis 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).MethodsWe 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.ResultsNineteen 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.ConclusionsSGLT-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 registrationhttps://inplasy.com/inplasy-2022-12-0061/, identifier 2022120061.

Type 2 Diabetes and Chronic Kidney Disease: An Opportunity for Pharmacists to Improve Outcomes

“…Other limitations of treatment may include the requirement for regular monitoring of blood pressure and volume status [ 5 ]. SGLT-2is may also be associated with muscle atrophy, and as T2D is a further risk factor for sarcopenia, patients should be assessed for other relevant risk factors, such as age, weight, and muscle mass when considering this type of treatment [ 65 ].…”

Drug‐related sarcopenia as a secondary sarcopenia

“…Sodium-glucose cotransporter 2 inhibitors that decrease proximal tubular glucose reabsorption, not only reduce body weight and body fat, but meta-analyses have indicated that they also reduce lean body mass and skeletal muscle mass. 25,26 Sodiumglucose cotransporter 2 itself is not present in skeletal muscle, and its effects on skeletal muscle may be mediated by indirect systemic effects. Possible mechanisms include decreased uptake of glucose and amino acids and increased degradation of muscle proteins in skeletal muscle associated with decreased insulin secretion, but the detailed mechanisms remain unclear (Tables 2 and 3).…”

“…Sodium–glucose cotransporter 2 inhibitors that decrease proximal tubular glucose reabsorption, not only reduce body weight and body fat, but meta‐analyses have indicated that they also reduce lean body mass and skeletal muscle mass 25,26 . Sodium–glucose cotransporter 2 itself is not present in skeletal muscle, and its effects on skeletal muscle may be mediated by indirect systemic effects.…”