Background
Methods
Study population
Study protocol
Measurements of biochemical parameters
Endpoints
Statistical analysis
Results
Baseline characteristics
Variable | Sitagliptin n = 40 | Voglibose n = 40 |
P value |
---|---|---|---|
Age, y | 67.8 ± 10.5 | 66.7 ± 9.8 | 0.654 |
Women, n (%) | 20(50) | 14(35) | 0.258 |
Diabetes duration, months (95 % CI) | 48(6-240) | 38.5(3-218) | 0.145 |
Body mass index, kg/m2 | 27.7 ± 4.1 | 25.7 ± 4.3 | 0.038 |
Abdominal girth, cm | 88.7 ± 14.3 | 85.9 ± 15.6 | 0.469 |
Current smoking | 6(15) | 4(10) | 0.762 |
Regular alcohol drinkers | 13(33) | 17(43) | 0.489 |
NYHA functional class | |||
Class I, n (%) | 17(43) | 17(43) | 1.000 |
Class II, n (%) | 23(58) | 22(55) | |
Class III, n (%) | 0(0) | 1(3) | |
Grades of Diastolic Dysfunction | |||
0 | 1 (2.6) | 3 (7.5) | 0.0987 |
1 | 31 (79.5) | 34 (85.0) | |
2 | 7 (17.9) | 3 (7.5) | |
Diabetes complication+ | 7(18) | 3(8) | 0.311 |
Diabetic retinopathy | 4(10) | 2(5) | 0.675 |
Diabetic nephropathy | 3(8) | 0(0) | 0.241 |
Diabetic neuropathy | 2(5) | 0(0) | 0.494 |
Hypertension | 37(93) | 32(80) | 0.193 |
Hyperuricemia | 31(78) | 31(78) | 1.000 |
Hyperlipidemia | 5(13) | 4(10) | 1.000 |
Renal disturbance | 7(18) | 1(3) | 0.057 |
Mean eGFR | 74.8 ± 21.7 | 70.5 ± 15.3 | 0.304 |
Cerebrovascular disease | 3(8) | 1(3) | 0.615 |
Myocardial infarction | 5(13) | 2(5) | 0.432 |
Peripheral artery disease | 3(8) | 1(3) | 0.615 |
Anti-diabetic drugs | |||
Pioglitazone | 14(35) | 18(45) | 0.494 |
Sulfonylurea | 6(15) | 3(8) | 0.481 |
Metformin | 7(18) | 1(3) | 0.057 |
α-GI | 1(3) | 0(0) | 1.000 |
Antihypertensive drugs | |||
ARB | 28(70) | 27(68) | 1.000 |
Calcium channel blocker | 26(65) | 22(55) | 0.494 |
Diuretics | 15(38) | 10(25) | 0.335 |
Others | 11(28) | 10(25) | 1.000 |
ACE-I | 2(5) | 3(8) | |
α-blocker | 4(10) | 1(3) | |
β-blocker | 6(15) | 4(10) | |
αβ-blocker | 1(3) | 1(3) | |
Aldosterone antagonist | 2(5) | 1(3) | |
Antihyperlipidemic drugs | |||
Statins | 24(60) | 22(55) | 0.821 |
Fibrate | 2(5) | 2(5) | 1.000 |
Ezetimibe | 5(13) | 6(15) | 1.000 |
Eicosapentaenoic acid | 5(13) | 2(5) | 0.432 |
Antiplatelet agent | 10(25) | 12(30) | 0.803 |
Nitrates | 1(3) | 1(3) | 1.000 |
Allopurinol | 1(3) | 4(10) | 0.359 |
Uricosuric agents | 0(0) | 1(3) | 1.000 |
The primary endpoint
Variable | Sitagliptin n = 40 | Voglibose n = 40 | Between-group difference |
---|---|---|---|
e’ | |||
Baseline at 0W | 5.6 ± 1.3 | 5.5 ± 1.1 | p = 0.664 |
at 24W | 5.8 ± 1.3 | 5.8 ± 1.1 | p = 0.997 |
Δe’: 24W-0W | 0.2 ± 1.1 | 0.3 ± 0.9 | p = 0.702 |
E/e’ | |||
Baseline at 0W | 12.8 ± 4.3 | 11.6 ± 2.1 | p = 0.109 |
at 24W | 12.4 ± 3.4 | 11.1 ± 2.7 | p = 0.060 |
ΔE/e’: 24W-0W | -0.3 ± 2.5 | -0.5 ± 2.3 | p = 0.804 |
Dependent variable | Independent variable | Estimate | 95 % CI |
P value | |
---|---|---|---|---|---|
e’ (24W) | e’ (0W) | 0.525 | 0.309 | 0.742 | <0.0001 |
Sitagliptin/Voglibose | -0.047 | -0.455 | 0.362 | 0.821 | |
Age — yr | -0.028 | -0.054 | -0.003 | 0.032 | |
without/with TZD | 0.547 | 0.130 | 0.965 | 0.011 | |
E/e’ (24W) | E/e’ (0W) | 0.615 | 0.471 | 0.758 | <0.0001 |
Sitagliptin/Voglibose | 0.688 | -0.239 | 1.615 | 0.144 | |
Age — yr | 0.024 | -0.025 | 0.072 | 0.334 | |
without/with TZD | -1.411 | -2.339 | -0.483 | 0.003 |
Model | e’ [cm/s] | E/e’ | ||||
---|---|---|---|---|---|---|
Change from baseline | P valueb
| R2 | Change from baseline | P valueb
| R2 | |
Beta (95 % CI) | Beta (95 % CI) | |||||
Model1—Primary model | 0.500 | 0.609 | ||||
Baseline | 0.525 (0.309 to 0.742) | <.0001 | 0.615 (0.471 to 0.758) | <.0001 | ||
Sitagliptin/Voglibose | -0.047 (-0.455 to 0.362) | 0.8206 | 0.688 (-0.239 to 1.615) | 0.1436 | ||
Age—yr | -0.028 (-0.054 to -0.003) | 0.0317 | 0.024 (-0.025 to 0.072) | 0.3335 | ||
Without/with TZD | 0.547 (0.130 to 0.965) | 0.0109 | -1.411 (-2.339 to -0.483) | 0.0034 | ||
Model2—Add demographic valuesb
| 0.522 | 0.641 | ||||
Baseline | 0.520 (0.298 to 0.742) | <.0001 | 0.603 (0.456 to 0.750) | <.0001 | ||
Sitagliptin/Voglibose | -0.069 (-0.504 to 0.365) | 0.7509 | 0.683 (-0.271 to 1.636) | 0.1576 | ||
Age—yr | -0.025 (-0.052 to 0.002) | 0.0739 | 0.013 (-0.037 to 0.064) | 0.5964 | ||
Female/Male | 0.243 (-0.195 to 0.681) | 0.2718 | -1.114 (-2.092 to -0.137) | 0.0261 | ||
BMI (0W) | 0.033 (-0.019 to 0.084) | 0.2140 | -0.037 (-0.155 to 0.081) | 0.5306 | ||
SBP (0W) | -0.005 (-0.020 to 0.011) | 0.5454 | -0.002 (-0.036 to 0.031) | 0.8917 | ||
Pulse (0W) | -0.003 (-0.025 to 0.019) | 0.7882 | 0.022 (-0.028 to 0.071) | 0.3911 | ||
Without/with TZD | 0.662 (0.216 to 1.108) | 0.0042 | -1.732 (-2.711 to -0.753) | 0.0007 | ||
Model3—Add complicationsb
| 0.518 | 0.626 | ||||
Baseline | 0.487 (0.253 to 0.721) | <.0001 | 0.584 (0.425 to 0.744) | <.0001 | ||
Sitagliptin/Voglibose | 0.018 (-0.426 to 0.462) | 0.9362 | 0.642 (-0.331 to 1.615) | 0.1922 | ||
Age—yr | -0.031 (-0.057 to -0.004) | 0.0228 | 0.030 (-0.020 to 0.081) | 0.2389 | ||
Diabetes complication | -0.395 (-1.038 to 0.247) | 0.2238 | 0.721 (-0.799 to 2.241) | 0.3473 | ||
Hypertension | 0.202 (-0.410 to 0.814) | 0.5131 | -0.527 (-1.908 to 0.854) | 0.4491 | ||
Hyperlipidemia | 0.219 (-0.317 to 0.755) | 0.4177 | -0.886 (-2.086 to 0.313) | 0.1450 | ||
Renal disturbance | -0.219 (-1.000 to 0.562) | 0.5780 | 0.277 (-1.453 to 2.007) | 0.7502 | ||
Without/with TZD | 0.511 (0.068 to 0.954) | 0.0244 | -1.302 (-2.271 to -0.334) | 0.0092 | ||
Model4—Add laboratory valuesb
| 0.525 | 0.642 | ||||
Baseline | 0.542 (0.314 to 0.770) | <.0001 | 0.615 (0.469 to 0.761) | <.0001 | ||
Sitagliptin/Voglibose | -0.127 (-0.568 to 0.314) | 0.5671 | 0.669 (-0.314 to 1.651) | 0.1790 | ||
Age—yr | -0.023 (-0.053 to 0.006) | 0.1220 | 0.029 (-0.027 to 0.084) | 0.3045 | ||
WBC (0W) | -0.000 (-0.000 to 0.000) | 0.7030 | 0.000 (-0.000 to 0.000) | 0.2013 | ||
AST (0W) | 0.012 (-0.008 to 0.032) | 0.2398 | 0.003 (-0.040 to 0.046) | 0.8871 | ||
BUN (0W) | 0.009 (-0.045 to 0.063) | 0.7380 | -0.019 (-0.139 to 0.101) | 0.7498 | ||
Glucagon (0W) | -0.001 (-0.012 to 0.010) | 0.8296 | -0.010 (-0.034 to 0.014) | 0.3929 | ||
Adiponectin (0W) | -0.017 (-0.049 to 0.016) | 0.3067 | -0.030 (-0.102 to 0.041) | 0.4020 | ||
IVSTh (0W) | -0.192 (-1.847 to 1.463) | 0.8175 | -1.323 (-5.000 to 2.353) | 0.4749 | ||
Without/with TZD | 0.380 (-0.181 to 0.941) | 0.1808 | -1.675 (-2.916 to -0.434) | 0.0089 | ||
Model5—Add adiponectinc
| 0.511 | 0.620 | ||||
Baseline | 0.516 (0.299 to 0.732) | <.0001 | 0.623 (0.480 to 0.766) | <.0001 | ||
Sitagliptin/Voglibose | -0.080 (-0.490 to 0.330) | 0.6991 | 0.587 (-0.344 to 1.519) | 0.2129 | ||
Age—yr | -0.025 (-0.051 to 0.001) | 0.0637 | 0.033 (-0.016 to 0.083) | 0.1858 | ||
Adiponectin (0W) | -0.018 (-0.047 to 0.011) | 0.2169 | -0.046 (-0.112 to 0.019) | 0.1610 | ||
Without/with TZD | 0.388 (-0.099 to 0.876) | 0.1169 | -1.807 (-2.884 to -0.730) | 0.0013 | ||
Model6—Remove TZD | 0.493 | 0.560 | ||||
Baseline | 0.480 (0.266 to 0.695) | <.0001 | 0.624 (0.472 to 0.777) | <.0001 | ||
Sitagliptin/Voglibose | -0.067 (-0.481 to 0.347) | 0.7471 | 0.566 (-0.429 to 1.561) | 0.2605 | ||
Age—yr | -0.026 (-0.052 to 0.001) | 0.0580 | 0.025 (-0.028 to 0.078) | 0.3505 | ||
Adiponectin (0W) | -0.030 (-0.055 to -0.005) | 0.0187 | 0.010 (-0.050 to 0.070) | 0.7331 |
Secondary efficacy measures
Variable | Sitagliptin | Voglibose | Between-group difference | ||
---|---|---|---|---|---|
Mean ± SD |
P value | Mean ± SD |
P value |
P value | |
Glucose | |||||
Baseline at 0W | 145 ± 58 | 133 ± 42 | 0.304 | ||
At 24W | 127 ± 26 | 133 ± 27 | 0.354 | ||
24W-0W | -23 ± 60 | 0.047 | 1 ± 43 | 0.916 | 0.083 |
HbA1c | |||||
Baseline at 0W | 7.1 ± 0.7 | 6.9 ± 0.5 | 0.273 | ||
At 24W | 6.4 ± 0.4 | 6.7 ± 0.5 | 0.026 | ||
24W-0W | -0.7 ± 0.6 | <0.0001 | -0.3 ± 0.4 | 0.0004 | 0.002 |
GIP | |||||
Baseline at 0W | 191 ± 214 | 159 ± 211 | 0.517 | ||
At 24W | 149 ± 161 | 162 ± 148 | 0.759 | ||
24W-0W | -21 ± 226 | 0.314 | 0.6 ± 1.6 | 0.041 | 0.749 |
CD34 | |||||
Baseline at 0W | 1.1 ± 0.7 | 0.9 ± 0.6 | 0.239 | ||
At 24W | 1.1 ± 0.5 | 0.9 ± 0.7 | 0.160 | ||
24W-0W | 0.1 ± 0.5 | 0.435 | 0.0 ± 0.5 | 0.772 | 0.430 |
Total cholesterol | |||||
Baseline at 0W | 184 ± 27 | 185 ± 33 | 0.944 | ||
At 24W | 178 ± 29 | 183 ± 37 | 0.522 | ||
24W-0W | -3 ± 30 | 0.603 | 0 ± 29 | 0.991 | 0.709 |
Triglyceride | |||||
Baseline at 0W | 155 ± 107 | 141 ± 74 | 0.486 | ||
At 24W | 132 ± 62 | 127 ± 72 | 0.803 | ||
24W-0W | -15 ± 94 | 0.391 | -13 ± 52 | 0.190 | 0.905 |
HDL-C | |||||
Baseline at 0W | 51 ± 12 | 56 ± 16 | 0.106 | ||
At 24W | 52 ± 14 | 53 ± 15 | 0.930 | ||
24W-0W | 0.8 ± 7.9 | 0.551 | -3.6 ± 8.2 | 0.010 | 0.021 |
Adiponectin | |||||
Baseline at 0W | 11.0 ± 8.3 | 13.3 ± 8.7 | 0.222 | ||
At 24W | 11.7 ± 8.8 | 12.9 ± 7.3 | 0.528 | ||
24W-0W | 0.5 ± 1.8 | 0.092 | -0.3 ± 2.9 | 0.539 | 0.150 |
MDA-LDL | |||||
Baseline at 0W | 106 ± 34 | 110 ± 37 | 0.658 | ||
At 24W | 113 ± 34 | 109 ± 36 | 0.591 | ||
24W-0W | 9 ± 32 | 0.118 | 1 ± 38 | 0.860 | 0.364 |
8-OHdG | |||||
Baseline at 0W | 11.7 ± 7.9 | 13.5 ± 10.0 | 0.392 | ||
At 24W | 11.4 ± 7.4 | 14.8 ± 14.6 | 0.221 | ||
24W-0W | -0.2 ± 10.0 | 0.903 | 1.5 ± 16.9 | 0.596 | 0.605 |
hs-CRP | |||||
Baseline at 0W | 3869 ± 9072 | 1358 ± 2511 | 0.099 | ||
At 24W | 1933 ± 5101 | 661 ± 691 | 0.147 | ||
24W-0W | -1929 ± 6798 | 0.098 | -380 ± 1186 | 0.059 | 0.186 |
PTX-3 | |||||
Baseline at 0W | 1.8 ± 1.0 | 2.4 ± 2.7 | 0.206 | ||
At 24W | 1.5 ± 0.8 | 1.6 ± 0.8 | 0.557 | ||
24W-0W | -0.3 ± 0.7 | 0.006 | -0.3 ± 1.2 | 0.104 | 0.974 |
e-GFR | |||||
Baseline at 0W | 75 ± 22 | 71 ± 15 | 0.304 | ||
At 24W | 69 ± 19 | 72 ± 16 | 0.411 | ||
24W-0W | -5 ± 12 | 0.014 | 0 ± 9 | 0.903 | 0.036 |
BNP, pg/ml | |||||
Baseline at 0W | 39 ± 48 | 34 ± 35 | 0.600 | ||
At 24W | 40 ± 41 | 28 ± 24 | 0.160 | ||
24W-0W | 1 ± 40 | 0.923 | -5 ± 22 | 0.164 | 0.443 |
Variable | Sitagliptin | Voglibose | Between-group difference | ||
---|---|---|---|---|---|
Mean ± SD |
P value | Mean ± SD |
P value |
P value | |
SBP, mmHg | |||||
Baseline at 0W | 135 ± 16 | 131 ± 13 | 0.180 | ||
At 24W | 128 ± 10 | 129 ± 15 | 0.855 | ||
24W-0W | -7 ± 17 | 0.022 | -2 ± 15 | 0.496 | 0.184 |
DBP, mmHg | |||||
Baseline at 0W | 74 ± 13 | 75 ± 10 | 0.818 | ||
At 24W | 71 ± 10 | 75 ± 11 | 0.108 | ||
24W-0W | -2 ± 14 | 0.344 | 1 ± 10 | 0.779 | 0.349 |
Pulse, b.p.m. | |||||
Baseline at 0W | 71 ± 11 | 71 ± 10 | 0.903 | ||
At 24W | 69 ± 12 | 71 ± 11 | 0.483 | ||
24W-0W | -1 ± 12 | 0.653 | 0 ± 12 | 0.816 | 0.625 |
Body weight | |||||
Baseline at 0W | 69 ± 10 | 67 ± 12 | 0.294 | ||
At 24W | 68 ± 11 | 67 ± 13 | 0.736 | ||
24W-0W | -1.3 ± 3.2 | 0.018 | 0.4 ± 2.8 | 0.433 | 0.020 |
a’, cm/s | |||||
Baseline at 0W | 8.4 ± 1.6 | 9.0 ± 1.6 | 0.110 | ||
At 24W | 8.1 ± 1.8 | 9.0 ± 1.6 | 0.031 | ||
24W-0W | -0.3 ± 1.7 | 0.316 | 0.2 ± 1.4 | 0.468 | 0.214 |
s’, cm/s | |||||
Baseline at 0W | 6.6 ± 1.1 | 7.2 ± 1.2 | 0.019 | ||
At 24W | 6.8 ± 1.4 | 7.0 ± 1.1 | 0.609 | ||
24W-0W | 0.2 ± 1.4 | 0.398 | -0.2 ± 1.4 | 0.412 | 0.237 |
Dct | |||||
Baseline at 0W | 234 ± 41 | 237 ± 39 | 0.769 | ||
At 24W | 236 ± 42 | 233 ± 43 | 0.765 | ||
24W-0W | 1 ± 41 | 0.885 | -4 ± 35 | 0.525 | 0.604 |
E velocity, m/s | |||||
Baseline at 0W | 68 ± 16 | 62 ± 11 | 0.048 | ||
At 24W | 69 ± 14 | 63 ± 14 | 0.047 | ||
24W-0W | 1 ± 10 | 0.569 | 0 ± 12 | 0.879 | 0.803 |
A velocity, m/s | |||||
Baseline at 0W | 82 ± 19 | 79 ± 18 | 0.421 | ||
At 24W | 80 ± 19 | 74 ± 14 | 0.150 | ||
24W-0W | -1 ± 13 | 0.537 | -4 ± 10 | 0.020 | 0.299 |
E/A ratio | |||||
Baseline at 0W | 0.9 ± 0.3 | 0.8 ± 0.2 | 0.424 | ||
At 24W | 0.9 ± 0.2 | 0.9 ± 0.3 | 0.668 | ||
24W-0W | 0.0 ± 0.2 | 0.402 | 0.0 ± 0.2 | 0.157 | 0.651 |
Septal thickness, mm | |||||
Baseline at 0W | 1.0 ± 0.2 | 0.9 ± 0.1 | 0.069 | ||
At 24W | 0.9 ± 0.1 | 0.9 ± 0.1 | 0.502 | ||
24W-0W | 0.0 ± 0.1 | 0.015 | 0.0 ± 0.1 | 0.876 | 0.083 |
LVEF, % | |||||
Baseline at 0W | 68 ± 7 | 71 ± 7 | 0.209 | ||
At 24W | 68 ± 6 | 66 ± 9 | 0.179 | ||
24W-0W | 0 ± 8 | 0.967 | -5 ± 8 | 0.001 | 0.013 |
LVMI, g/m2 | |||||
Baseline at 0W | 93 ± 20 | 85 ± 18 | 0.085 | ||
At 24W | 90 ± 17 | 86 ± 18 | 0.239 | ||
24W-0W | -3 ± 13 | 0.195 | 1 ± 14 | 0.551 | 0.183 |
LA volume index, ml/m2 | |||||
Baseline at 0W | 27.7 ± 5.9 | 26.1 ± 7.6 | 0.346 | ||
At 24W | 27.7 ± 7.5 | 26.6 ± 6.3 | 0.508 | ||
24W-0W | 0.3 ± 5.0 | 0.734 | 0.8 ± 5.6 | 0.448 | 0.733 |
Urine albumin, mg/g/Cr | |||||
Baseline at 0W | 37 ± 66 | 31 ± 41 | 0.603 | ||
At 24W | 39 ± 94 | 28 ± 50 | 0.533 | ||
24W-0W | -1 ± 50 | 0.889 | -5 ± 30 | 0.339 | 0.723 |
BUN | |||||
Baseline at 0W | 17 ± 5 | 16 ± 5 | 0.760 | ||
At 24W | 16 ± 3 | 16 ± 4 | 0.824 | ||
24W-0W | 0 ± 3 | 0.759 | 0 ± 4 | 0.740 | 0.959 |
Adverse events
Events | Sitagliptin | Voglibose |
---|---|---|
n = 40 | n = 40 | |
2 cases (5.0) | 4 cases (10.0) | |
Hypoglycemia | 1 (2.5) | 0 (0.0) |
Diarrhea | 0 (0.0) | 4 (10.0) |
Edema | 0 (0.0) | 3 (7.5) |
Gastrointestinal symptom | 0 (0.0) | 2 (5.0) |
Liver dysfunction | 1 (2.5) | 0 (0.0) |
Total events | 2 | 9 |