Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

Abstract

Objective Type 2 diabetes mellitus(T2DM) is closely related to sarcopenic obesity(SO). Body composition measurement including body weight, body mass index, waist circumference, percentage body fat, fat mass, muscle mass, visceral adipose tissue and subcutaneus adipose tissue, plays a key role in evaluating T2DM and SO. The weight reduction effect of sodium-glucose cotransporter 2(SGLT-2) inhibitors has been demonstrated. However, 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 randomized controlled trials was conducted to evaluate the effect of SGLT-2 inhibitors on body composition in T2DM. Methods PubMed, the Cochrane Library, EMbase and Web of Science databases were searched by computer. All statistical analyses were carried out with Review Manager version 5. 3. Results were compared by weight mean difference(WMD), with 95% confidence intervals(CI) for continuous outcomes. A random effects model was applied regardless of heterogeneity. The I2 statistic was applied to evaluate the heterogeneity of studies. Publication bias was assessed using Funnel plots. Results 18 studies with 1430 participants were eligible for the meta-analysis. SGLT-2 inhibitors significantly reduced body weight(WMD:-2. 73kg, 95%CI: -3. 32 to -2. 13, p<0. 00001), body mass index(WMD:-1. 13kg/m2, 95%CI: -1. 77 to -0. 50, p = 0. 0005), waist circumference(WMD:-2. 20cm, 95%CI: -3. 81 to -0. 58, p = 0. 008), visceral fat area(MD:-14. 79cm2, 95%CI: -24. 65 to -4. 93, p = 0. 003), subcutaneous fat area(WMD:-23. 27cm2, 95% CI:-46. 44 to -0. 11, P = 0. 05), fat mass(WMD:-1. 16kg, 95%CI: -2. 01 to -0. 31, p = 0. 008), percentage body fat(WMD:-1. 50%, 95%CI:-2. 12 to -0. 87, P<0. 00001), lean mass(WMD:-0. 76kg, 95%CI:-1. 53 to 0. 01, P = 0. 05) and skeletal muscle mass(WMD:-1. 01kg, 95%CI:-1. 91 to -0. 11, P = 0. 03). Conclusion SGLT-2 inhibitors improve body composition in T2DM 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. 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 effect of the reduction in muscle mass by SGLT-2 inhibitors in T2DM should be considered.

Recent advances in the treatment of patients with obesity and chronic kidney disease

“…While there is an increase in the relative risk of adverse reactions (mycotic genital infection, UTI, and lower limb amputation), the absolute benefit currently outweighs the risk. Several meta-analyses involving the above trials have demonstrated a positive weight loss outcome with SGLT2i compared to placebo [ 48 , 49 ]. However, to date, there are no published trials of SGLT2i specifically in patients with obesity.…”

Efficacy and safety of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin in elderly Japanese adults (≥65 years) with type 2 diabetes: A randomized, double‐blind, placebo‐controlled, 52‐week clinical trial (EMPA‐ELDERLY)

“…11,12 Conversely, a meta-analysis of 18 small, short (median 24 weeks), randomized trials of SGLT2is (including nine in Japan) reported an overall significant reduction of skeletal muscle mass [À1.01 kg; 95% confidence interval (CI) À1.91, À0.11]. 13 However, these studies included younger people with higher body mass index (BMI), and the effects remain to be investigated specifically in older patients with T2D where extreme caution is appropriate because of higher risk of muscle weakness and frailty. Therefore, we evaluated the SGLT2i empagliflozin in elderly Japanese adults with T2D with regard to its effects on glycaemia, muscle mass, muscle strength and physical performance, as well as safety.…”

“…Randomized, open‐label, 24‐week trials of dapagliflozin or ipragliflozin added to other anti‐diabetes drugs in patients with T2D in Japan did not find loss of skeletal muscle mass 11,12 . Conversely, a meta‐analysis of 18 small, short (median 24 weeks), randomized trials of SGLT2is (including nine in Japan) reported an overall significant reduction of skeletal muscle mass [−1.01 kg; 95% confidence interval (CI) −1.91, −0.11] 13 . However, these studies included younger people with higher body mass index (BMI), and the effects remain to be investigated specifically in older patients with T2D where extreme caution is appropriate because of higher risk of muscle weakness and frailty.…”

Urinary α1 microglobulin level is useful for selecting sodium‐glucose transporter 2 inhibitor or metformin for visceral fat reduction in patients with type 2 diabetes

“…Visceral adipose tissue, accurately measured using computed tomography (CT), is an independent risk marker of cardiovascular and metabolic diseases, while visceral fat reduction ameliorates metabolic disorders 2 . Some studies reported that SGLT2 inhibitors significantly reduced visceral fat area (VFA) 3 and metformin reduced visceral fat 4 …”