Using sodium-glucose cotransporter 2(SGLT-2) inhibitors improves body composition in T2DM patients including body weight, body mass index, waist circumference, visceral fat area, subcutaneous fat area, percentage body fat and fat mass reduction - but cause adverse effects of reducing muscle mass – according to outcomes of a meta-analysis of randomised controlled trials by researchers from Cangzhou Central Hospital, Cangzhou, Hebei Province, China. The findings were featured in the paper, ‘Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials’, published in PLOS One.
The authors noted that although the positive impact of SGLT-2 inhibitors has been well documented, there are warnings that SGLT-2 inhibitors should be used with caution because they may increase the risk of sarcopenia:
“The effect of SGLT-2 inhibitors on body composition in T2DM is inconclusive. In this work, a meta-analysis of randomised controlled trials was conducted to evaluate the effect of SGLT-2 inhibitors on body composition in T2DM.”
They identified 18 studies and 1,430 participants (726 SGLT-2 inhibitors participants and 704 control participants), including seven multi-centre studies and 11 single-centre studies, for the meta-analysis. SGLT-2 inhibitors groups include canagliflozin (3 studies), dapagliflozin (8 studies), empagliflozin (3 studies) and ipragliflozin (4 studies), meanwhile control groups include traditional hypoglycaemic drugs (16 studies), such as sulfonylureas, insulin, metformin, thiazolidinediones, DPP-4 inhibitors, etc and another new class of hypoglycaemic drugs, GLP-1 receptor agonists(GLP-1RAs)(2 studies). All studies were high-quality parallel grouped studies.
Outcomes
The meta-analysis showed that SGLT-2 inhibitors treatment significantly decreased body weight compared with other drugs (Weight mean difference (WMD):-2. 73kg, 95%CI: -3. 32 to -2. 13, p<0.00001). Seven RCTs reported BMI in 234 SGLT-2 inhibitors users and 219 non-users. In this meta-analysis, SGLT-2 inhibitors treatment significantly decreased BMI compared with other drugs (WMD:-1. 13kg/m2, 95%CI: -1. 77 to -0. 50, p=0.0005). Four studies evaluated the effects of SGLT-2 inhibitors on waist circumference (WC). Overall analysis showed that SGLT-2 inhibitors significantly reduced WC (WMD:-2. 20cm, 95%CI: -3. 81 to -0. 58, p=0.008).
Eight studies of 429 participants showed that SGLT-2 inhibitors significantly decreased VFA compared with other antihyperglycemic drugs (MD:-14. 79cm2, 95%CI: -24. 65 to -4. 93, p=0.003). Six studies evaluated the effects of SGLT-2 inhibitors on SFA. Overall analysis showed that SGLT-2 inhibitors significantly decreased SFA (WMD:-23. 27cm2, 95% CI:-46. 44 to -0. 11, p=0.05).
Ten studies of 827 participants showed that SGLT-2 inhibitors significantly decreased fat mass (FM) compared with other antihyperglycemic drugs (WMD:-1. 16kg, 95%CI: -2. 01 to -0. 31, p=0.008). There were four studies that reported the effect of SGLT-2 inhibitors on percentage body fat (PBF). In contrast with the control group, SGLT-2 inhibitors evidently reduced PBF (WMD:-1. 50%, 95%CI:-2. 12 to -0. 87, p<0.00001). Nine studies evaluated the effects of SGLT-2 inhibitors on lean mass (LM). Overall analysis showed that SGLT-2 inhibitors significantly decreased LM compared with other antihyperglycemic drugs (WMD:-0. 76kg, 95%CI:-1. 53 to 0. 01, p=0.05). Seven studies in 206 SGLT-2 inhibitors users and 201 non-users evaluated the skeletal muscle mass (SMM). Overall analysis showed that SGLT-2 inhibitors significantly reduced SMM compared with other antihyperglycemic (WMD:-1. 01kg, 95%CI:-1. 91 to -0. 11, p=0.03).
“The highlight of this meta-analysis is to confirm not only the advantages of SGLT-2 inhibitors in improving body composition, such as weight loss, BMI, WC, VFA, SFA, PBF and FM reduction, but also the adverse effects of these drugs on muscle mass reduction,” the authors noted. “…the studies included in the meta-analysis are from different ethnic groups, age ranges, genders and patient groups with comorbidities, and that there are many parameters that may affect muscle loss, suggesting that pre-planned prospective control and large-scale studies will be more instructive in this regard…Therefore, until more evidence is obtained to support that SGLT-2 inhibitors increase the risk of sarcopenia, not only the benefit on body composition, but also the adverse effects of the reduction on muscle mass by SGLT-2 inhibitors in T2DM should be considered.”
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