Why carry out this study?
|
Altered body composition plays a significant role in the pathogenesis and prognosis of type 2 diabetes mellitus. |
Sodium–glucose cotransporter 2 (SGLT2) inhibitors are new glucose-lowering drugs that reduce body weight, but their effect on body composition remains uncertain. |
This review aimed to investigate the association of SGLT2 inhibitors and body composition in type 2 diabetes mellitus. |
What was learned from the review?
|
SGLT2 inhibitors reduce total body weight in people with type 2 diabetes mellitus. Reduction of body weight is primarily due to the loss of fat mass. |
In long-term studies, loss of fat-free mass approximately contributes 35% of body weight reduction. This change is comparable to the body composition changes reported after lifestyle interventions and bariatric surgery. |
The impact of SGLT2 inhibitors on body composition significantly differs from sulfonylureas and dipeptidyl peptidase 4 inhibitors, but it is similar to glucagon-like peptide 1 receptor agonists. |
Introduction
Type 2 Diabetes Mellitus and Body Composition
Mechanism of Action of Sodium–Glucose Cotransporter 2 Inhibitors on Body Composition
Methods for Evaluating Body Composition
Compartment | Definition |
---|---|
Fat mass | Mass of adipose tissue |
Fat-free mass | Total body mass except fat mass |
Lean body mass | Fat-free mass except for mineral content (bones) |
Skeletal muscle mass | Lean body mass minus connective tissue, skin, and other organs |
Methods
Ethical Approval
Results and Discussion
Study | Year, country | Population | Intervention | Sample size | Age (years) | Baseline BMI (kg/m2) | Concurrent medications |
---|---|---|---|---|---|---|---|
Bolinder et al. [53] | 2012, multicenter | T2DM | Dapagliflozin 10 mg/day | 91 | 60.6 ± 8.2 | 32.1 ± 3.9 | Exclusive treatment with metformin |
Placebo | 89 | 60.8 ± 6.9 | 31.7 ± 3.9 | ||||
Bolinder et al. [52] | 2014, multicenter | T2DM | Dapagliflozin 10 mg/day | 69 | 60.6 ± 8.2 | 32.1 ± 3.9 | Exclusive treatment with metformin |
Placebo | 71 | 60.8 ± 6.9 | 31.7 ± 3.9 | ||||
Blonde et al. [51] | 2016, multicenter | T2DM | Canagliflozin 100 mg/day | 63 | 64.3 ± 6.6 | 30.9 ± 4.8 | Antihyperglycemic agents |
Canagliflozin 300 mg/day | 73 | 63.0 ± 6.0 | 31.6 ± 4.3 | ||||
Placebo | 75 | 64.2 ± 6.4 | 32.0 ± 5.5 | ||||
Fadini et al. [62] | 2017, Italy | T2DM | Dapagliflozin 10 mg/day | 15 | 66.3 ± 1.8 | 28.4 ± 1.4 | Oral glucose-lowering drugs or insulin |
Placebo | 16 | 61.0 ± 1.8 | 32.8 ± 1.4 | ||||
Inoue et al. [69] | 2019, Japan | T2DM | Ipragliflozin 50 mg/day | 24 | 60.5 ± 9.8 | 27.9 ± 4.0 | Insulin alone or plus oral hypoglycemic agents |
Placebo | 24 | 60.8 ± 12.1 | 27.7 ± 4.5 | ||||
Chehregosha et al. [56] | 2021, Iran | T2DM/NAFLD | Empagliflozin 10 mg | 35 | 50.5 ± 8.4 | 30.9 ± 3.3 | NR |
Pioglitazone | 34 | 52.5 ± 7.9 | 29.4 ± 3.7 | ||||
Placebo | 37 | 51.8 ± 7.8 | 30.2 ± 4.4 | ||||
Lauritsen et al. [58] | 2021, Denmark | T2DM | Empagliflozin 25 mg/day vs. placebo (crossover design) | 13 | 62 ± 6 | 31.5 ± 5.0 | Metformin |
Horibe et al. [68] | 2022, Japan | T2DM | Dapagliflozin 5 mg/day | 26 | 59.7 ± 12.0 | 28.0 ± 4.0 | Oral hypoglycemic agents other than SGLT2i |
Placebo | 24 | 62.3 ± 6.5 | 27.6 ± 3.8 | ||||
Brandt-Jacobsen et al. [54] | 2023, Denmark | T2DM | Empagliflozin 25 mg/day | 38 | 65.7 ± 9.1 | 32.8 ± 5.6 | Unspecified glucose-lowering treatment |
Placebo | 40 | 66.4 ± 8.7 | 30.3 ± 5.9 | ||||
Nakaguchi et al. [60] | 2020, Japan | T2DM | Empagliflozin 10 mg/day | 31 | 66.3 ± 9.5 | 25.8 ± 4.1 | Insulin |
Liraglutide | 30 | 67.2 ± 9.0 | 26.4 ± 4.6 | ||||
McCrimmon et al. [59] | 2020, multicenter | T2DM | Canagliflozin 300 mg/day | 90 | 58.6 ± 10.1 | 32.3 ± 5.5 | Metformin |
Semaglutide | 88 | 57.8 ± 9.9 | 32.6 ± 6.4 | ||||
Cefalu et al. [55] | 2013, multicenter | T2DM | Canagliflozin 100 mg/day | 111 | NR | NR | Metformin |
Canagliflozin 300 mg/day | 102 | ||||||
Glimepiride | 96 | ||||||
Kitazawa et al. [64] | 2020, Japan | T2DM | Tofogliflozin 20 mg/day | 33 | 57.3 ± 11.4 | 25.3 ± 3.9 | Metformin and DPP4 inhibitors |
Glimepiride | 31 | 57.6 ± 9.3 | 25.4 ± 3.8 | ||||
Wolf et al. [61] | 2021, Brazil | T2DM | Dapagliflozin 10 mg/day | 44 | 58 ± 7 | 30 (7) | Up to two oral hypoglycemic agents |
Glibenclamide | 45 | 58 ± 7 | 30 (7) | ||||
Tsurutani et al. [50] | 2018, multicenter | T2DM | Ipragliflozin 50 mg/day | 60 | 53.5 ± 11.72 | 28.8 (6.3) | Patients with prior use of SGLT2is or incretin-related agents were excluded |
Sitagliptin | 59 | 54.0 ± 10.7 | 28.5 (5.2) | ||||
Zeng et al. [67] | 2022, Taiwan | T2DM | Empagliflozin 25 mg/day | 46 | 58.9 ± 9.9 | 27.7 ± 5.0 | Premixed insulin with or without OAD |
Linagliptin | 51 | 58.7 ± 10.2 | 28.0 ± 3.5 | ||||
Kato et al. [63] | 2017, Japan | T2DM | Dapagliflozin 5 mg/day vs. control (Cross-over design) | Preceding group = 27 | 48.7 ± 11.5 | 30.3 ± 5.3 | Insulin or antidiabetic drugs |
Following group = 29 | 49.4 ± 11.8 | 29.6 ± 4.9 | |||||
Shimizu et al. [65] | 2018, Japan | T2DM/NAFLD | Dapagliflozin 5 mg/day | 33 | 56.2 ± 11.5 | 27.6 ± 4.7 | Three OAD with or without insulin |
Control | 24 | 57.1 ± 13.8 | 28.3 ± 3.5 | ||||
Yamakage et al. [66] | 2020, Japan | T2DM | Dapagliflozin 5 mg/day | 27 | 58.4 ± 13.0 | 31.3 ± 7.6 | Sulfonylureas, biguanides, alpha-glucosidase, DPP4 inhibitors, or their combination |
Control | 27 | 60.7 ± 11.9 | 30.7 ± 6.2 | ||||
Han et al. [57] | 2020, Korea | T2DM | Ipragliflozin 50 mg/day | 30 | 52.5 ± 10.3 | 30.4 ± 5.4 | Metformin and pioglitazone combination for at least 8 weeks |
Control | 15 | 56.7 ± 11.8 | 30.2 ± 2.5 |
Effect of Treatment Duration on Body Composition
Author, year, country | Assessment method | Duration (weeks) | Body composition indices in SGLT2is groupa (kg) | ||||||
---|---|---|---|---|---|---|---|---|---|
Baseline BW | BW change | Baseline fat mass | Fat mass change | Baseline fat-free massb | Fat-free mass change | ||||
Compared to placebo | |||||||||
1 | Bolinder et al. (2012), [53] | DXA | 24 | 92.1 | − 2.96* | 33.6 | − 2.22* | 56.2 | − 1.1* |
2 | Bolinder et al. (2014), [52] | DXA | 102 | 92.1 | − 4.54* | 33.7 | − 2.80 | 55.3 | − 1.30 |
3 | Blonde et al. [51] | DXA | 26 | 100: 88.9 300: 93.2 | − 2.5* − 3.2* | 32.2 33.8 | − 1.9* − 2.4* | 51.2 53.2 | − 0.9* − 1.2* |
4 | Fadini et al. [62] | BIA | 12 | NR | − 3.1* | NR | − 0.1 | NR | − 2.9* |
5 | Inoue et al. [69] | DXA/BIA | 24 | 72.34 | − 2.78* | DXA: 23.29 BIA: 22.14 | DXA: − 2.07* BIA: − 2.21* | DXA: 41.63 BIA: 47.14 | DXA: − 0.6 BIA: − 0.56 |
6 | Chehregosha et al. [56] | DXA | 24 | 82.2 | − 2.7* | NR | NR | NR | NR |
7 | Lauritsen et al. [58] | DXA | 4 | 95.2 | − 0.6 | 31.4 | − 0.2 | 60.4 | − 1.0* |
8 | Horibe et al. [68] | DXA/ BIA | 24 | 73.29 | − 2.40* | DXA: 25.43 BIA: 23.27 | DXA: − 2.32* BIA: − 1.73* | DXA: 45.86 BIA: 47.92 | DXA: − 0.17 BIA: − 0.64 |
9 | Brandt–Jacobsen et al. [54] | DXA | 13 | 97.1 | − 1.40* | 30.2 | − 0.9* | 67.4 | − 0.49 |
Compared to GLP-1 receptor agonists | |||||||||
10 | Nakaguchi et al. [60] | DXA | 24 | 69.0 | − 1.5 | 19.2 | − 0.7 | 46.1 | − 0.6 |
11 | McCrimmon et al. [59] | DXA | 52 | 87.6 | − 4.1 | 32.5 | − 2.62 | 51.3 | − 1.48 |
Compared to sulfonylureas | |||||||||
12 | Cefalu et al. [55] | DXA | 52 | 100 mg: 84.4 300 mg: 85.9 | − 4.4* − 4.2* | 28.2 29.3 | NR | 47.7 44.6 | − 0.9* − 1.1* |
13 | Kitazawa et al. [64] | BIA | 24 | 67.0 | − 2.0* | 19.4 | − 0.7* | 47.6 | − 1.3* |
14 | Wolf et al. [61] | DXA | 12 | 81.6 | − 2.7* | 29.9 | − 2.0* | 51.3 | − 0.34* |
Compared to DPP4 inhibitors | |||||||||
15 | Tsurutani et al. [50] | NR | 12 | NR | − 2.2* | NR | NR | NR | NR |
16 | Zeng et al. [67] | BIA | 24 | 71.4 | − 1.55* | 20.8 | − 1.02 | 46.5 | − 0.44* |
Compared to conventional treatment | |||||||||
17 | Kato et al. [63] | BIA | 12 | Grp 1: 80.0 Grp 2: 81.7 | Grp 1: − 1.2 Grp 2: − 3.2 | NR | Grp 1: − 1.39 Grp 2: − 1.97 | NR | Grp 1: − 0.12 Grp 2: − 0.22 |
18 | Shimizu et al. [65] | BIA | 24 | 73.6 | − 2.9* | NR | NR | 27.8 | − 0.9* |
19 | Yamakage et al. [66] | BIA | 24 | 80.5 | − 3.2* | NR | NR | 25.9 | 0.1 |
20 | Han et al. [57] | DXA | 24 | 84.2 | − 1.6* | 24.7 | − 1.0 | 56.6 | − 0.8 |