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

**Authors:** Runzhou Pan, Yan Zhang, Rongrong Wang, Yao Xu, Hong Ji, Yongcai Zhao, Gulali Aktas, Gulali Aktas, Gulali Aktas

PMC · DOI: 10.1371/journal.pone.0279889 · PLOS ONE · 2022-12-30

## TL;DR

This study finds that SGLT-2 inhibitors help reduce fat in type 2 diabetes patients but may also lower muscle mass, suggesting a need for caution.

## Contribution

The study provides a meta-analysis showing specific body composition changes from SGLT-2 inhibitors in type 2 diabetes.

## Key findings

- SGLT-2 inhibitors significantly reduce body weight, BMI, and fat mass in T2DM patients.
- They also lower visceral and subcutaneous fat but may reduce lean and skeletal muscle mass.
- The findings suggest a potential risk of sarcopenia despite benefits in fat reduction.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Diseases:** type 2 diabetes mellitus (MONDO:0005148)

## Full-text entities

- **Genes:** GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, FMOD (fibromodulin) [NCBI Gene 2331] {aka FM, SLRR2E}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}
- **Diseases:** abdominal obesity (MESH:D056128), FM loss (MESH:D016388), Type 1 Diabetes Mellitus (MESH:D003922), dehydration (MESH:D003681), non-alcoholic fatty liver disease (MESH:D065626), gestational diabetes (MESH:D016640), cardiovascular, diabetes and kidney diseases (MESH:D003928), diabetes (MESH:D003920), weight loss (MESH:D015431), SO (MESH:D009765), coronary heart disease (MESH:D003327), physical dysfunction (MESH:D059445), Loss of Muscle Mass (MESH:C536030), inflammation (MESH:D007249), water loss (MESH:D000069578), T2DM (MESH:D003924), insulin resistance (MESH:D007333), muscle loss (MESH:D009135), sarcopenia (MESH:D055948), muscle fiber atrophy (MESH:D009133), euglycemic ketoacidosis (MESH:D007662), Euglycemic Diabetic Ketoacidosis (MESH:D016883),  (MESH:D001835)
- **Chemicals:** Sotagliflozin (MESH:C575681), A1c (-), sulfonylureas (MESH:D013453), Ipragliflozin (MESH:C572941), thiazolidinediones (MESH:D045162), glucose (MESH:D005947), Pioglitazone (MESH:D000077205), Canagliflozin (MESH:D000068896), Linagliptin (MESH:D000069476), Tofogliflozin (MESH:C575086), Empagliflozin (MESH:C570240), Luseogliflozin (MESH:C549343), Ertugliflozin (MESH:C570288), Dapagliflozin (MESH:C529054), Metformin (MESH:D008687), amino acids (MESH:D000596), Glimepiride (MESH:C057619)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC9803203/full.md

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Source: https://tomesphere.com/paper/PMC9803203