Table 2.
Changes in variables according to quartiles of percentage change in HICCIR at week 24 after administration of tofogliflozin
| Variables | Quartile 1(%Δ HICCIR a < +5.5) | Quartile 2(+5.5 ≤ %Δ HICCIR a < +20.5) | Quartile 3(+20.5 ≤ %Δ HICCIR a < +35.5) | Quartile 4(+35.5 ≤ %Δ HICCIR a) | P |
|---|---|---|---|---|---|
| N | 76 | 76 | 77 | 76 | |
| Fasting insulin (%) | −5.5 (3.3) | −24.9 (3.3)*** | −23.7 (3.3)*** | −31.1 (3.3)*** | <0.001 |
| Fasting C‐peptide (%) | −5.3 (2.7)* | −10.7 (2.7)*** | −10.0 (2.7)*** | −9.8 (2.7)*** | 0.49 |
| Fasting glucagon (%) | 0.59 (2.08) | −2.18 (2.08) | 1.53 (2.07) | −2.10 (2.08) | 0.48 |
| Insulin AUC0‐120min (%) | 17.4 (2.2)*** | −10.2 (2.2)*** | −19.4 (2.1)*** | −30.6 (2.2)*** | <0.001 |
| C‐peptide AUC0‐120min (%) | 11.3 (2.3)*** | 1.8 (2.3) | 3.3 (2.3) | 3.4 (2.3) | 0.02 |
| Glucagon AUC0‐120min (%) | −4.1 (1.7)* | −2.3 (1.7) | −2.3 (1.7) | −3.7 (1.7)* | 0.81 |
| HICCIR b (%) | −4.4 (1.0)*** | 13.5 (1.0)*** | 28.2 (1.0)*** | 50.1 (1.0)*** | <0.001 |
| Total GLP‐1 AUC0‐120min (%) | 7.2 (4.3) | 6.5 (4.3) | 2.1 (4.3) | 4.2 (4.3) | 0.83 |
| Active GLP‐1 AUC0‐120min (%) | 24.1 (5.1)*** | 27.6 (5.1)*** | 28.9 (5.0)*** | 41.4 (5.1)*** | 0.09 |
| Matsuda index (%) | 32.9 (5.6)*** | 64.6 (5.6)*** | 70.2 (5.6)*** | 92.7 (5.6)*** | <0.001 |
| iHOMA2%Sc (%) | 27.7 (5.9)*** | 53.3 (5.9)*** | 51.1 (5.8)*** | 64.6 (5.9)*** | <0.001 |
| iHOMA2%βc (%) | 65.8 (7.3)*** | 26.1 (7.3)*** | 32.2 (7.3)** | 19.9 (7.3)** | <0.001 |
| HbA1cd (%) | −0.88 (0.06)*** | −0.80 (0.06)*** | −0.74 (0.06)*** | −0.73 (0.06)*** | 0.23 |
| Fasting plasma glucosed (mg/dL) | −32.9 (1.9)*** | −33.2 (1.9)*** | −30.6 (1.9)*** | −32.4 (1.9)*** | 0.77 |
| Glucose AUC0‐120min d (mg/dL·2 h) | −112.3 (5.6)*** | −110.0 (5.6)*** | −98.5 (5.6)*** | −103.7 (5.6)*** | 0.29 |
| Body weight (%) | −3.4 (0.3)*** | −4.8 (0.3)*** | −4.5 (0.3)*** | −4.9 (0.3)*** | <0.01 |
| Waist circumference (%) | −2.7 (0.5)*** | −2.3 (0.5)*** | −2.8 (0.5)*** | −3.0 (0.5)*** | 0.69 |
| eGFR (%) | 4.4 (1.7)** | −1.2 (1.7) | 0.2 (1.6) | −0.9 (1.7) | 0.07 |
| LDL‐C (%) | 1.3 (1.9) | −1.2 (1.9) | 0.9 (1.9) | −0.4 (1.9) | 0.77 |
| HDL‐C (%) | 2.9 (1.6) | 5.1 (1.6)** | 7.9 (1.6)*** | 10.5 (1.6)*** | <0.01 |
| ln‐TG (ln[mg/dL]) | −0.06 (0.04) | −0.15 (0.04)*** | −0.23 (0.04)*** | −0.20 (0.04)** | 0.01 |
| AST (%) | −9.5 (2.1)*** | −10.5 (2.1)*** | −6.3 (2.1)** | −7.6 (2.1)*** | 0.49 |
| ALT (%) | −14.3 (2.6)*** | −20.1 (2.6)*** | −19.4 (2.6)*** | −20.5 (2.6)*** | 0.29 |
| ɤGTP (%) | −18.8 (2.9)*** | −21.9 (2.9)*** | −20.0 (2.8)*** | −19.0 (2.9)*** | 0.86 |
| Fatty liver indexe (%) | −18.3 (2.9)*** | −27.6 (2.9)*** | −29.2 (2.9)*** | −31.2 (2.9)*** | 0.01 |
| Fatty liver at week 24, n (%) | 37 (48.7) | 35 (46.1) | 44 (57.1) | 32 (42.1) | 0.30 |
| Fasting free fatty acid (%) | 17.6 (5.6)** | 22.3 (5.6)*** | 30.7 (5.6)*** | 34.6 (5.6)*** | 0.13 |
| Adiponectin (%) | 11.4 (2.2)*** | 13.3 (2.2)*** | 12.0 (2.2)*** | 12.6 (2.2)*** | 0.94 |
| ln‐β‐hydroxybutyrate (ln[μmol/L]) | 0.43 (0.09)*** | 0.61 (0.09)*** | 0.75 (0.09)*** | 0.82 (0.09)*** | 0.02 |
Note: ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; BMI, body mass index; eGFR, estimated glomerular filtration rate; GLP‐1, glucagon‐like peptide 1; ɤGTP, ɤ‐glutamyl transpeptidase; HbA1c, glycated haemoglobin; TG, triglycerides.Data are expressed as mean (standard error).Analyses were performed by ANOVA across quartiles for the following variables; fasting insulin, fasting C‐peptide, fasting glucagon, insulin AUC0‐120min, C‐peptide AUC0‐120min, glucagon AUC0‐120min, HICCIR, total GLP‐1 AUC0‐120min, active GLP‐1 AUC0‐120min, Matsuda index, iHOMA2S and iHOMA2β.Data are expressed as least squares mean (standard error).Analyses were performed by ANCOVA adjusted baseline values for the following variables: HbA1c, fasting plasma glucose, glucose AUC0‐120min, body weight, waist circumference, fasting free fatty acid, adiponectin, LDL‐C, HDL‐C, ln‐transformed TG, AST, ALT, ɤGTP, fatty liver index and ln‐transformed β‐hydroxybutyrate.Proportion of fatty liver was analysed by Fisher’s exact test.*P < 0.05, **P < 0.01, ***P < 0.001 vs. baseline (t‐test for least squares mean).
Percentage change from baseline in HICCIR.
C‐peptide AUC0‐120min/insulin AUC0‐120min ratio.
From the iHOMA2 model.
HbA1c, fasting plasma glucose and glucose AUC0‐120min were evaluated as absolute changes from baseline to week 24.
Fatty liver index (e0.953 × ln[TG] + 0.139 × BMI + 0.718 × ln(ɤGTP) + 0.053 × waist circumference – 15.745)/(1 + e0.953 × ln[TG] + 0.139 × BMI + 0.718 × ln[ɤGTP] + 0.053 × waist circumference – 15.745) × 100.