Table 1. Effect of SGLT-2 inhibitors on body weight and waist circumference in Asian patients with T2DM.
| Study | Design and population | Intervention | Effect on body weight | Effect on waist circumference |
|---|---|---|---|---|
| Monotherapy | ||||
| Inagaki et al. (2013) [79] | Phase II, 12-wk randomized study; Japanese T2DM (n=383) | Canagliflozin (50, 100, 200, or 300 mg); placebo | −1.98 kg (50 mg); −2.51 kg (100 mg); −2.39 kg (200 mg); −3.19 kg (300 mg); −0.78 kg (placebo) | −1.59 cm (50 mg), −1.81 cm (100 mg), −1.83 cm (200 mg), −2.21 cm (300 mg); −0.59 cm (placebo) |
| Inagaki et al. (2014) [73] | Phase III, 24-wk double-blind randomized study; Japanese T2DM (n=272) | Canagliflozin (100, 200 mg); placebo | −3.76% (100 mg), −4.02% (200 mg); −0.76% (placebo) | −2.21 cm (100 mg); −2.82 cm (200 mg); −1.03 cm (placebo) |
| Kaku et al. (2013) [80] | Phase II, 12-wk randomized study; Japanese T2DM (n=279) | Dapagliflozin (1, 2.5, 5, or 10 mg/day); placebo | −1.25 kg (1 mg); −1.24 kg (2.5 mg); −2.06 kg (5 mg); −1.91 kg (10 mg); −0.05 (placebo) | - |
| Ji et al. (2014) [74] | Phase III, 24-wk double-blind randomized study; drug-naïve Asian T2DM (n=393) | Dapagliflozin (5 or 10 mg); placebo | −1.64 kg (5 mg); −2.25 kg (10 mg); −0.27 kg (placebo) | −2.77 cm (5 mg); −2.20 cm (10 mg); −0.72 cm (placebo) |
| Kaku et al. (2014) [81] | Phase III, 24-wk double-blind randomized study; Japanese T2DM (n=261) | Dapagliflozin (5 or 10 mg); placebo | −2.13 kg (5 mg); −2.22 kg (10 mg); −0.84 kg (placebo) | - |
| Kadowaki et al. (2014) [82] | Phase II, 12-wk randomized study; Japanese T2DM (n=547) | Empagliflozin (5, 10, 25, or 50 mg); placebo | −2.5 kg (5 mg); −2.6 kg (10 mg); −2.9 kg (25 mg); −3.1 kg (50 mg); −0.9 kg (placebo) | −2.4 cm (5 mg); −2.3 cm (10 mg); −2.6 cm (25 mg); −2.6 cm (50 mg); −1.3 cm (placebo) |
| Kadowaki et al. (2015) [75] | 40-wk extension study; Japanese T2DM (n=532) | Empagliflozin (10, 25 mg) | −3.1 kg (10 mg); −3.1 kg (25 mg) | −2.8 cm (10 mg); −2.8 cm (25 mg) |
| Kashiwagi et al. (2014) [66] | Phase II, 12-wk randomized study; Japanese T2DM (n=361) | Ipragliflozin (12.5, 25, 50, or 100 mg/day); placebo | −1.46 kg (12.5 mg); −1.69 kg (25 mg); −1.81 kg (50 mg); −2.1 kg (100 mg); −0.39 kg (placebo) | - |
| Kashiwagi et al. (2015) [83] | Phase III, 16-wk double-blind randomized study; Japanese T2DM (n=131) | Ipragliflozin (50 mg); placebo | −2.31 kg (50 mg); −1.03 kg (placebo) | −1.61 cm (50 mg); −0.41 cm (placebo) |
| Seino et al. (2015) [67] | 52-wk open-label study; Japanese T2DM (n=299) | Luseogliflozin (2.5 mg, option to uptitrate to 5 mg) | 12 wk: −1.77 kg (2.5/5 mg) 24 wk: −1.91 kg (2.5/5 mg) 36 wk: −2.35 kg (2.5/5 mg) 52 wk: −2.68 kg (2.5/5 mg) | - |
| Hirose et al. (2016) [84] | 8-wk open-label study (n=17) | Tofogliflozin (20 mg) | −1.1 kg (20 mg) | - |
| Kaku et al. (2014) [65] | Phase II/III, 24-wk double-blind randomized study; Japanese T2DM (n=235) | Tofogliflozin (10, 20, or 40 mg); placebo | −2.23 kg (10 mg); −2.85 kg (20 mg); −2.97 kg (40 mg); −0.36 kg (placebo) | −2.42 cm (10 mg); −2.47 cm (20 mg); −2.27 cm (40 mg); 0.02 cm (placebo) |
| Add-on to oral antidiabetic agents | ||||
| Ji et al. (2015) [85] | Phase III, 18-wk double-blind randomized study; Asian T2DM (n=678) | Canagliflozin (100, 300 mg)+Met or SU+Met; placebo | −1.9 kg (100 mg); –2.1 kg (300 mg); –0.5 kg (placebo) | - |
| Inagaki et al. (2015) [72] | 52-wk open-label randomized study; Japanese T2DM (n=1,299) | Canagliflozin (100, 200 mg); other GLDs | −4.42% (100 mg); −4.70% (200 mg); −2.94% (100 mg+SU); −3.51% (200 mg+SU); −3.97% (100 mg+glinide); −4.37% (200 mg+glinide); −4.03% (100 mg+α-GI); −4.98% (200 mg+α-GI); −4.42% (100 mg+BG); −5.54% (200 mg+BG); −3.37% (100 mg+TZD); −3.43% (200 mg+TZD); −4.00% (100 mg+DPP-4i); −4.37% (200 mg+DPP-4i) | −2.76 cm (100 mg); −3.34 cm (200 mg); −1.96 cm (100 mg+SU); −1.72 cm (200 mg+SU); −2.93 cm (100 mg+glinide); −3.24 cm (200 mg+glinide); −2.27 cm (100 mg+α-GI); −2.57 (200 mg+α-GI); −3.40 cm (100 mg+BG); −3.82 cm (200 mg+BG); −3.12 cm (100 mg+TZD); −2.64 cm (200 mg+TZD); −3.34 cm (100 mg+DPP-4i); −2.37 cm (200 mg+DPP-4i) |
| Kadowaki et al. (2017) [86] | Phase III, 24-wk double-blind randomized study; Japanese T2DM (n=138) | Canagliflozin (100 mg); teneligliptin; placebo | −2.29 kg (100 mg+teneligliptin); −0.78 kg (placebo+teneligliptin) | - |
| Kadowaki et al. (2018) [87] | 52-wk open-label study; Japanese T2DM (n=153) | Canagliflozin (100 mg); teneligliptin | −2.86 kg (100 mg+teneligliptin) | - |
| Harashima et al. (2018) [68] | Phase IV, 52-wk open-label; Japanese T2DM (n=71) | Canagliflozin (100 mg); liraglutide | −3.29 kg (100 mg+liraglutide) | −3.39 cm (100 mg+liraglutide) |
| Kaku et al. (2014) [81] | Phase III, 52-wk open-label study; Japanese T2DM (n=728) | Dapagliflozin (5 mg, option to uptitrate to 10 mg); other GLDs | −2.6 kg (monotherapy); −2.1 kg (combination therapy) | −2.1 cm (monotherapy); −2.0 cm (combination therapy) |
| Yang et al. (2016) [78] | Phase III, 24-wk randomized doubleblind study; Asian T2DM (n=444) | Dapagliflozin (5, 10 mg); Met; placebo | −1.8 kg (5 mg+Met); −2.6 kg (10 mg+Met); −0.7 kg (placebo+Met) | −1.96 cm (5 mg+Met); −2.15 cm (10 mg+Met); −0.39 cm (placebo+Met) |
| Araki et al. (2015) [88] | Phase III, 52-wk randomized study; Japanese T2DM (n=1,160) | Empagliflozin (10, 25 mg); other GLDs | SU: −2.3 kg (10 mg+SU); −2.8 kg (25 mg+SU) BG: −3.9 kg (10 mg+BG); −3.4 kg (25 mg+BG) TZD: −2.6 kg (10 mg+TZD); −2.8 kg (25 mg+TZD) α-GI: −3.8 kg (10 mg+α-GI); −3.4 kg (25 mg+α-GI) DPP-4i: −2.9 kg (10 mg+DPP-4i); −2.8 kg (25 mg+DPP-4i) Glinide: −2.6 kg (10 mg+glinide); −3.1 kg (25 mg+glinide) | - |
| Kashiwagi et al. (2015) [89] | Phase III, 24-wk randomized study; Japanese T2DM (n=168) | Ipragliflozin (50 mg); Met; placebo | −2.33 kg (50 mg+Met); −0.63 kg (placebo+Met) | −2.39 cm (50 mg+Met); −0.48 cm (placebo+Met) |
| Lu et al. (2016) [76] | Phase III, 24-wk randomized doubleblind study; Asian T2DM (n=171) | Ipragliflozin (50 mg); Met; placebo | −2.93 kg (50 mg+Met); −1.70 kg (placebo+Met) | −1.72 cm (50 mg+Met); −0.85 cm (placebo+Met) |
| Kashiwagi et al. (2015) [90] | Phase III, 24-wk randomized doubleblind study; Japanese T2DM (n=152) | Ipragliflozin (50 mg); pioglitazone; placebo | −2.29 kg (50 mg+pioglitazone); 0.51 kg (placebo+pioglitazone) | −1.82 cm (50 mg+pioglitazone); 0.14 cm (placebo+pioglitazone) |
| Kashiwagi et al. (2015) [91] | Phase III, 24-wk randomized doubleblind study; Japanese T2DM (n=243) | Ipragliflozin (50, 100 mg); SU; placebo | −2.33 kg (50 mg+SU); −0.88 kg (placebo+SU) | −1.61 cm (50 mg+SU); −0.87 cm (placebo+SU) |
| Seino et al. (2018) [69] | 52-wk, open-label study; Japanese T2DM (n=76) | Luseogliflozin (2.5 mg, option to uptitrate to 5 mg); liraglutide | 12 wk: −1.65 kg (2.5/5 mg+GLP-RA) 12 wk: −2.52 kg (2.5/5 mg+GLP-RA) 36 wk: −2.86 kg (2.5/5 mg+GLP-RA) 52 wk: −2.71 kg (2.5/5 mg+GLP-RA) | 12 wk: −1.39 cm (2.5/5 mg+GLP-RA) 12 wk: −2.63 cm (2.5/5 mg+GLP-RA) 36 wk: −3.09 cm (2.5/5 mg+GLP-RA) 52 wk: −2.86 cm (2.5/5 mg+GLP-RA) |
| Ikeda et al. (2015) [92] | Phase II, 12-wk randomized, doubleblind study (n=398) | Tofogliflozin (2.5, 5, 10, 20, or 40 mg); Met; placebo | −1.56 kg (2.5 mg+Met); −1.85 kg (5 mg+Met); −2.24 kg (10 mg+Met); −2.55 kg (20 mg+Met); −2.82 kg (40 mg+Met); −0.74 kg (placebo+Met) | - |
| Add-on to insulin | ||||
| Inagaki et al. (2016) [93] | Phase IV, 16-wk double-blind randomized study; Japanese T2DM (n=146) | Canagliflozin (100 mg); insulin; placebo | −1.49 kg (100 mg+insulin); 0.15 kg (placebo+insulin) | - |
| Inagaki et al. (2018) [94] | Phase IV, 52-wk (16-wk double-blind randomized placebocontrolled study+36wk open-label extension); Japanese T2DM (n=146) | Canagliflozin (100 mg); insulin; placebo | −0.99 kg (placebo+insulin → 100 mg+insulin); −1.52 kg (100 mg+insulin → 100 mg+insulin) | - |
| Araki et al. (2016) [70] | Phase IV, 16-wk double-blind randomized placebo-controlled study; Japanese T2DM (n=182) | Dapagliflozin (5 mg); insulin; placebo | −0.55 kg (5 mg+insulin); 0.66 kg (placebo+insulin) | Placebo-corrected mean reduction: −1.00 cm |
| Araki et al. (2017) [71] | 36-wk open-label extension of Araki et al. 2016 [70] (n=175) | Dapagliflozin (5 mg); insulin | −1.5 kg (5 mg+insulin → 5 mg+insulin); −1.37 kg (placebo+insulin → 100 mg+insulin) | −1.4 cm (5 mg+insulin → 5 mg+insulin); −0.9 cm (placebo+insulin → 100 mg+insulin) |
| Yang et al. (2018) [95] | Phase III, 24-wk randomized doubleblind study; Asian T2DM (n=272) | Dapagliflozin (10 mg); insulin; placebo | −1.00 kg (10 mg+insulin); 0.37 kg (placebo+insulin) | −0.70 cm (10 mg+insulin); 0.00 cm (placebo+insulin) |
| Ishihara et al. (2016) [96] | Phase IV, 16-wk double-blind randomized placebo-controlled study; Japanese T2DM (n=262) | Ipragliflozin (50 mg); insulin; placebo | −1.09 kg (10 mg+insulin); −0.05 kg (placebo+insulin) | −1.36 cm (10 mg+insulin); −0.84 cm (placebo+insulin) |
| Seino et al. (2018) [77] | Phase IV, 52-wk (16-wk double-blind randomized placebo-controlled study+36-wk openlabel extension); Japanese T2DM (n=233) | Luseogliflozin (2.5 mg); insulin; placebo | −1.32 kg (2.5 mg+insulin); −0.05 kg (placebo+insulin) | −1.16 cm (2.5 mg+insulin); 0.04 cm (placebo+insulin) |
| Terauchi et al. (2017) [97] | Phase IV, 16-wk double-blind randomized placebo-controlled study; Japanese T2DM (n=211) | Tofogliflozin (20 mg); insulin; placebo | −1.34 kg (20 mg+insulin); 0.03 kg (placebo+insulin) | - |
| Terauchi et al. (2018) [98] | 36-wk open-label extension of Terauchi et al. (2017) [97] (n=210) | Tofogliflozin (20 mg); insulin | −1.52 kg (20 mg+insulin → 20 mg+insulin); −2.13 kg (placebo+insulin → 20 mg+insulin) | - |
| Suzuki et al. (2016) [99] | 24-wk randomized active-controlled study; Japanese T2DM (n=53) | Tofogliflozin (20 mg); insulin; insulin glargine | 0.6 kg (insulin); −2.9 kg (20 mg+insulin); −3.4 kg (20 mg+insulin glargine) | - |
| Pooled analyses | ||||
| John et al. (2016) [100] | Pooled data from four 26-wk placebo-controlled studies (n=2,313) and a 104-wk active-controlled study (n=1,450) in T2DM patients in hot climate countries | Canagliflozin (100, 300 mg); placebo; glim+Met; canagliflozin (100, 300 mg)+Met | Placebo-controlled trials Hot climate subset: −1.9 kg (100 mg); −2.4 (300 mg); −0.3 kg (placebo) Other climate subset: −2.8 kg (100 mg); −3.4 kg (300 mg); −0.7 kg (placebo) Active-controlled trials Hot climate subset: −2.6 kg (100 mg+Met); −2.8 (300 mg+Met); +1.3 (glim+Met) Other climate subset: −3.9 kg (100 mg+Met); −3.9 (300 mg+Met); 0.6 (glim+Met) | - |
| Yang et al. (2017) [101] | Pooled data from eight Phase IIb/III double-blind placebo-controlled trials of up to 24 wk (n=1,453) | Dapagliflozin (5, 10 mg); placebo | −1.9 kg (5 mg); −2.4 kg (10 mg); −0.6 kg (placebo) | - |
| Yoon et al. (2016) [102] | Pooled data from four Phase III trials up to 24 wk (n=1,326) | Empagliflozin (10, 25 mg); placebo, other GLDs | Pooled data: −1.6 kg (10 mg); −1.8 kg (10 mg) Monotherapy: −1.7 kg (10 mg); −2.1 kg (25 mg) Met: −1.4 kg (10 mg+Met); −1.5 kg (10 mg+Met) Met+SU: −1.5 kg (10 mg+Met+SU); −1.9 kg (10 mg+Met+SU) Pioglitazone: −2.0 kg (10 mg+pioglitazone); −1.7 kg (10 mg+pioglitazone) | |
| Prasanna Kumar et al. (2016) [103] | Pooled subgroup analysis of patients enrolled from India (n=124) in four randomized Phase III trials | Canagliflozin (100, 300 mg); placebo; other GLDs | Overall population: −2.6 (100 mg); −3.3 (300 mg) Indian subgroup: −1.7 (100 mg); −2.2 (300 mg) | |
| Seino et al. (2015) [104] | Pooled analysis of two 52-wk studies; Japanese T2DM (n=708) | Luseogliflozin (2.5 mg); other GLDs | SU: −2.23 kg (2.5 mg+SU) BG: −2.86 kg (2.5 mg+BG) DPP-4i: −1.96 kg (2.5 mg+DPP-4i) TZD: −2.32 kg (2.5 mg+TZD) Glinide: −2.88 kg (2.5 mg+glinide) α-GI: −2.80 kg (2.5 mg+α-GI) SU+placebo (24 wk): 0.16 kg (placebo+SU) | |
| Post-marketing study | ||||
| Utsunomiya et al. (2017) [105] | 1-yr prospective, observational, postmarketing study (n=1,424) | Tofogliflozin | −1.18 kg (4 wk); −1.81 kg (12 wk); −2.01 kg (24 wk); −1.72 kg (36 wk); −2.55 (52 wk) | |
| Nakamura et al. (2018) [106] | 24-mo post-marketing surveillance study (n=8,757) | Ipragliflozin | −1.32 kg (1 mo); −2.16 kg (3 mo); −2.45 kg (6 mo); −2.81 kg (12 mo); −3.11 (24 mo) |
SGLT-2, sodium glucose cotransporter-2; T2DM, type 2 diabetes mellitus; GLD, glucose-lowering drug; SU, sulfonylurea; α-GI, alpha glucosidase inhibitor; BG, biguanide; TZD, thiazolidinedione; DPP-4i, dipeptidyl peptidase-4 inhibitor; Met, metformin; GLP-RA, glucagon-like peptide-1 receptor agonist; glim, glimepiride.