Canagliflozin as a first-line drug fpr patients with type 2 diabetes mellitus appears to be beneficial in many aspects including glycemic control, body weight, uric acid (UA), insulin sensitivity, and beta-cell function, though certain precautions are required regarding its adverse events. |
Atherogenic cholesterols including non-high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol may be involved in the glycemic efficacy of canagliflozin. |
Some differences may exist between canagliflozin and ipragliflozin regarding their effect on metabolic markers in relation to their glycemic efficacies. |
1 Introduction
2 Subjects and Methods
2.1 Subjects
2.2 Laboratory Measurements
2.3 Data Analyses
3 Results
3.1 Safety and Tolerability of Canagliflozin Monotherapy as an Initial Therapy in Drug-Naïve Subjects with T2DM
3.2 Effect of Canagliflozin Monotherapy on Glycemic Parameters in Drug-Naïve Subjects with T2DM
Baseline | 3 months |
p values | % changes | |
---|---|---|---|---|
Age | 53.1 ± 14.0 | |||
F/M | 10/29 | |||
HbA1c (%) | 9.96 ± 2.52 | 8.33 ± 1.66 | <0.00001 | −16.3 |
FBG (mg/dL) | 193.4 ± 66.7 | 147.1 ± 32.4 | <0.00001 | −23.9 |
Insulin (μU/mL) | 9.45 ± 7.17 | 8.42 ± 6.26 | 0.077 | −10.8 |
HOMA-R | 4.50 ± 9.15 | 2.99 ± 2.17 | <0.00001 | −33.5 |
HOMA-B | 31.91 ± 30.12 | 41.52 ± 38.20 | <0.03 | 30.1 |
BMI | 26.84 ± 5.56 | 26.34 ± 5.50 | <0.00001 | −1.8 |
UA (mg/dL) | 5.35 ± 1.21 | 5.07 ± 1.19 | <0.05 | −5.2 |
T-C (mg/dL) | 219.1 ± 38.7 | 215.1 ± 39.1 | n.s. | −1.8 |
TG (mg/dL) | 187.2 ± 134.8 | 165.6 ± 95.8 | 0.057 | −11.5 |
HDL-C (mg/dL) | 52.4 ± 13.3 | 54.4 ± 12.2 | n.s. | 3.8 |
Non-HDL-C (mg/dL) | 166.6 ± 38.3 | 160.7 ± 39.6 | n.s. | −3.5 |
LDL-C (mg/dL) | 140.2 ± 37.8 | 137.1 ± 34.6 | n.s. | −2.2 |
0 | Coefficient | SE |
t value |
p value |
R
2
|
---|---|---|---|---|---|
(A) Canagliflozin
| |||||
Constant | −1.374 | 3.7421 | −0.36717 | 0.71658 | 0 |
Age | 0.024168 | 0.018375 | 1.3152 | 2.00E−01 | 0.024128 |
HbA1c | −0.83641 | 0.18562 | −4.506 | 0.000134 | 0.46652 |
FBG | 0.017085 | 0.009091 | 1.8794 | 0.071895 | 0.20613 |
Insulin | 0.047408 | 0.29753 | 0.15934 | 0.87468 | 0.053026 |
BMI | 0.028767 | 0.072687 | 0.39576 | 0.69564 | 0.020409 |
HOMA-R | −0.02944 | 0.45409 | −0.06483 | 0.94882 | 0.00085 |
HOMA-B | 0.005526 | 0.033547 | 0.16473 | 0.87048 | 0.15989 |
TG | −0.00905 | 0.003648 | −2.4803 | 0.020214 | 0.006131 |
HDL-C | 0.022281 | 0.018685 | 1.1925 | 0.24427 | 0.023862 |
Non-HDL-C | 0.058565 | 0.02184 | 2.6815 | 0.012794 | 0.00772 |
LDL-C | −0.05288 | 0.021241 | −2.4895 | 0.019805 | 9.82E−05 |
UA | 0.063483 | 0.22951 | 0.2766 | 0.78436 | 0.01183 |
(B) Ipragliflozin
| |||||
Constant | 5.0469 | 4.2932 | 1.1756 | 0.25509 | 0 |
Age | 0.019515 | 0.022548 | 0.86548 | 0.39816 | 0.15101 |
HbA1c | −0.48812 | 0.23057 | −2.117 | 0.048445 | 0.43358 |
FBG | −0.01283 | 0.009475 | −1.3542 | 0.19243 | 0.20424 |
Insulin | −0.21354 | 0.35315 | −0.60469 | 0.55293 | 0.011142 |
BMI | −0.09143 | 0.06348 | −1.4403 | 0.16696 | 0.066983 |
HOMA-R | 0.77484 | 0.58649 | 1.3212 | 0.203 | 0.010184 |
HOMA-B | −0.01357 | 0.03741 | −0.36264 | 0.7211 | 0.089243 |
TG | −0.00114 | 0.002732 | −0.4171 | 0.68154 | 0.091779 |
HDL-C | 0.002301 | 0.023205 | 0.099156 | 0.92211 | 0.050386 |
Non-HDL-C | 0.005596 | 0.01869 | 0.2994 | 0.76807 | 0.16314 |
LDL-C | −0.0071 | 0.018719 | −0.3794 | 0.70883 | 0.028367 |
UA | 0.19859 | 0.22846 | 0.86926 | 0.39615 | 0.070164 |
3.3 Effect of Canagliflozin on Non-Glycemic Parameters in Drug-Naïve Subjects with T2DM
3.4 Link Between the Changes in Metabolic Parameters
R
|
p values | |
---|---|---|
(A) Canagliflozin
| ||
ΔHbA1c vs. ΔFBG | 0.7443 | <0.00001 |
vs. Δinsulin | −0.3888 | <0.002 |
vs. ΔBMI | 0.2402 | n.s. |
vs. ΔHOMA-R | 0.0665 | n.s. |
vs. ΔHOMA-B | −0.6328 | <0.00001 |
vs. ΔTG | 0.0982 | n.s. |
vs. ΔHDL-C | −0.1198 | n.s. |
vs. Δnon-HDL-C | 0.3954 | <0.002 |
vs. ΔLDL-C | 0.4317 | <0.01 |
vs. ΔUA | −0.227 | n.s. |
(B) Ipragliflozin
| ||
ΔHbA1c vs. ΔFBG | 0.5524 | <0.001 |
vs. Δinsulin | −0.4864 | <0.005 |
vs. ΔBMI | 0.1836 | n.s. |
vs. ΔHOMA-R | −0.0342 | n.s. |
vs. ΔHOMA-B | −0.5813 | <0.0005 |
vs. ΔTG | 0.3978 | <0.05 |
vs. ΔHDL-C | −0.1665 | n.s. |
vs. Δnon-HDL-C | 0.1723 | n.s. |
vs. ΔLDL-C | −0.1091 | n.s. |
vs. ΔUA | −0.4309 | <0.02 |