1Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
2State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China
Copyright © 2022 Korean Diabetes Association
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Baseline variable | Dapagliflozin (n=30) | Sitagliptin (n=30) | P value | ||
---|---|---|---|---|---|
Clinical parameters | |||||
Men, % | 53.3 | 66.7 | 0.292 | ||
Age, yr | 56.9±10.7 | 60.6±7.03 | 0.120 | ||
Ever smoker, % | 40.0 | 40.0 | 1.000 | ||
Duration of diabetes, yr | 17.1±9.56 | 19.3±8.50 | 0.357 | ||
BMI, kg/m2 | 26.4±3.87 | 26.9±2.90 | 0.570 | ||
WC, cm | 92.7±8.28 | 92.9±8.19 | 0.949 | ||
Men | 94.8±8.96 | 95.0±6.85 | 0.952 | ||
Women | 90.3±6.98 | 88.6±9.34 | 0.615 | ||
Central obesity, % | 83.3 | 66.7 | 0.136 | ||
Systolic BP, mm Hg | 132±13.1 | 137±14.5 | 0.143 | ||
Diastolic BP, mm Hg | 73.1±7.27 | 75.6±7.99 | 0.207 | ||
Biochemistry parameters | |||||
Fasting glucose, mmol/L | 9.35±3.32 | 9.82±2.89 | 0.564 | ||
HbA1c, % | 8.94±0.60 | 8.79±0.56 | 0.321 | ||
HbA1c, mmol/mol | 74.20±6.57 | 72.60±6.11 | 0.321 | ||
C-peptide, nmol/L | 0.29 (0.19–0.39) | 0.28 (0.17–0.46) | 0.444 | ||
HDL-C, mmol/L | 1.25±0.34 | 1.24±0.41 | 0.945 | ||
HDL-CEC, % | 22.2±5.24 | 21.8±6.32 | 0.792 | ||
LDL-C, mmol/L | 2.08±0.64 | 1.86±0.77 | 0.235 | ||
Triglycerides |
1.15 (0.90–1.63) | 1.35 (0.88–2.18) | 0.328 | ||
ALT |
22 (16–37) | 23 (19–31) | 0.813 | ||
AST |
20 (18–29) | 22 (17–24) | 0.447 | ||
eGFR, mL/min/1.73 m2 | 90.4±19.6 | 81.2±16.1 | 0.050 | ||
≥60 mL/min/1.73 m2, % | 90.0 | 93.3 | 1.000 | ||
Albuminuria status | 0.865 | ||||
A1, % | 53.3 | 56.7 | |||
A2, % | 33.33 | 23.3 | |||
A3, % | 13.3 | 20.0 | |||
Fasting FFA, µmol/L | 91.5 (63.2–165) | 110 (86.6–160) | 0.278 | ||
Fasting BHB, µmol/L | 372 (315–521) | 401 (325–514) | 0.389 | ||
hsCRP |
0.96 (0.51–2.62) | 0.89 (0.42–2.49) | 0.341 | ||
VCTE | |||||
CAP, dB/m | 285±48.2 | 292±56.6 | 0.625 | ||
Minimal <248 dB/m | 23.3 | 20.0 | |||
Mild 248–267 dB/m | 16.7 | 23.3 | |||
Moderate 268–279 dB/m | 0.0 | 3.3 | |||
Severe >279 dB/m | 60.0 | 63.3 | |||
LS |
5.75 (4.33–8.95) | 6.10 (4.98–8.15) | 0.675 | ||
F0/1 <5.8 kPa | 50.0 | 46.7 | |||
F2 5.8–9.5 kPa | 36.7 | 43.3 | |||
F3 9.6–11.4 kPa | 6.6 | 3.3 | |||
F4 >11.4 kPa | 6.7 | 6.7 | |||
Medical diseases, % | |||||
Hypertension | 80.0 | 83.3 | 0.739 | ||
Coronary artery disease | 13.3 | 13.3 | 1.000 | ||
Stroke | 6.7 | 6.7 | 1.000 | ||
STDR | 6.7 | 10.0 | 1.000 | ||
Concomitant medications, % | |||||
Metformin | 100 | 100 | 1.000 | ||
Pioglitazone | 13.3 | 16.7 | 0.718 | ||
ACEI | 50.0 | 53.3 | 0.796 | ||
ARB | 27.7 | 26.7 | 1.000 | ||
Statin | 63.3 | 80.0 | 0.152 | ||
Fibrate | 0.0 | 10.0 | 0.237 | ||
Aspirin | 26.7 | 26.7 | 1.000 | ||
Total daily insulin dosage, units | 42.0±15.9 | 45.0±14.1 | 0.447 |
Baseline variable | Dapagliflozin (n=30) |
Sitagliptin (n=30) |
Change from baseline |
P value (Δchange) | ||||
---|---|---|---|---|---|---|---|---|
At baseline | At week 24 | At baseline | At week 24 | Dapagliflozin | Sitagliptin | |||
Primary outcome | ||||||||
BHB |
372 (315 to 521) | 472 (349 to 587) |
401 (325 to 514) | 403 (326 to 524) | 90.5 (–8.10 to 193) | –11.9 (–123 to 79.3) | 0.045 |
|
Secondary outcomes | ||||||||
Body weight, kg | 70.3±12.8 | 69.3±12.5 |
71.5±11.6 | 72.2±12.8 | –0.94±1.89 | 0.65±2.46 | 0.006 | |
WC, cm | 92.7±8.28 | 91.6±8.19 | 92.9±8.19 | 94.0±9.02 |
–1.09±4.47 | 1.11±2.90 | 0.028 | |
Systolic BP, mm Hg | 132±13.1 | 129±12.9 | 137±14.5 | 136±16.4 | –2.20±13.2 | –1.18±15.8 | 0.787 | |
Diastolic BP, mm Hg | 73.1±7.27 | 71.7±8.66 | 75.6±7.99 | 74.9±9.26 | –1.40±6.46 | –0.75±6.61 | 0.701 | |
Total daily insulin dose, units | 42.0±15.9 | 41.4±15.8 | 45.0±14.1 | 45.8±14.9 | –0.60±3.33 | 0.80±2.66 | 0.077 | |
FG, mmol/L | 9.35±3.32 | 7.21±2.11 |
9.82±2.89 | 6.79±2.02 |
–2.14±3.28 | –3.03±3.32 | 0.298 | |
HbA1c, % | 8.94±0.60 | 7.69±0.86 |
8.79±0.56 | 7.81±0.93 |
–1.25±0.78 | –0.98±0.80 | 0.198 | |
HbA1c, mmol/mol | 74.20±6.57 | 60.60±9.38 |
72.60±6.11 | 61.80±10.10 |
–13.60±0.56 | –10.70±8.78 | 0.198 | |
eGFR, mL/min/1.73 m2 | 91.9±18.1 | 90.2±19.8 | 81.2±16.1 | 77.7±15.6 |
–0.21±5.97 | –3.43±8.50 | 0.092 | |
HDL-C, mmol/L | 1.25±0.34 | 1.30±0.37 | 1.24±0.41 | 1.20±0.41 | 0.05±0.15 | –0.04±0.18 | 0.041 | |
LDL-C, mmol/L | 2.08±0.64 | 2.06±0.74 | 1.86± 0.77 | 1.76±0.62 | –0.02±0.47 | –0.11±0.62 | 0.545 | |
TG |
1.15 (0.90 to 1.63) | 1.15 (0.80 to 1.53) | 1.35 (0.88 to 2.18) | 1.25 (0.80 to 1.70) |
–0.15 (–0.40 to 0.10) | –0.25 (–0.50 to 0.05) | 0.611 | |
ALT |
21.5 (15.8 to 37.3) | 20.0 (15.8 to 27.5) | 22.5 (19.0 to 30.5) | 27.0 (19.8 to 32.0) | –1.00 (3.00 to –5.50) | 2.00 (–2.00 to 5.25) | 0.284 | |
AST |
20.0 (17.8 to 29.3) | 19.0 (16.8 to 25.0) | 21.5 (16.8–24.0) | 23.0 (20.8 to 27.3) |
0.00 (–3.50 to 2.00) | 3.00 (–1.00 to 5.25) | 0.160 | |
CAP, dB/m | 285±48.2 | 268±50.9 |
292±56.6 | 302 ± 58.0 | –17.8±40.6 | 10.0±37.0 | 0.007 | |
LS, kPa | 5.75 (4.33 to 8.95) | 5.15 (4.58 to 6.75) |
6.10 (4.98 to 8.15) | 7.00 (5.10 to 8.58) | –0.50 (–1.25 to 0.15) | 0.25 (–0.50 to 1.20) | 0.022 | |
HDL-CEC, % | 22.2±5.32 | 24.8±7.60 |
21.8± 6.32 | 21.3±6.43 | 2.66±5.14 | –0.50±6.71 | 0.045 | |
hsCRP |
0.96 (0.51 to 2.62) | 0.63 (0.42 to 2.05) | 0.89 (0.42 to 2.49) | 0.97 (0.42 to 2.22) | –0.19 (–0.95 to 0.002) | –0.10 (–0.60 to 0.63) | 0.177 | |
FFA |
91.6 (64.1 to 164) | 119 (69.0 to 164) | 110 (86.6 to 160) | 106 (56.6 to 174) | 9.58 (–41.8 to 45.0) | –6.72 (–43.6 to 26.5) | 0.191 |
Change in clinical and metabolic variable | Change in BHB levels, μmol/L |
|
---|---|---|
Crude r | P value | |
Body weight, kg | 0.111 | 0.560 |
Waist circumference, cm | –0.022 | 0.910 |
Systolic BP, mm Hg | 0.017 | 0.929 |
Diastolic BP, mm Hg | 0.239 | 0.204 |
Total daily insulin dose, units | 0.221 | 0.241 |
Fasting glucose, mmol/L | 0.068 | 0.723 |
HbA1c, % | 0.140 | 0.461 |
Triglyceride |
0.188 | 0.319 |
LDL-C, mmol/L | –0.344 | 0.063 |
HDL-C, mmol/L | –0.052 | 0.783 |
HDL-CEC, % | 0.107 | 0.575 |
ALT |
0.088 | 0.644 |
AST |
0.047 | 0.804 |
eGFR, mL/min/1.73 m2 | 0.011 | 0.956 |
CAP, dB/m | 0.239 | 0.204 |
LS |
–0.208 | 0.270 |
FFA |
0.433 | 0.017 |
hsCRP |
–0.206 | 0.274 |
Echocardiographic parameter | Dapagliflozin (n=25) |
Sitagliptin (n=25) |
Change from baseline |
P value (Δchange) | |||
---|---|---|---|---|---|---|---|
At baseline | At week 24 | At baseline | At week 24 | Dapagliflozin | Sitagliptin | ||
IVSd, mm | 11.00±1.42 | 11.30±1.55 | 11.50±1.55 | 11.40±1.76 | 0.18±1.20 | –0.47±1.07 | 0.374 |
LVPWd, mm | 9.40±1.58 | 9.26±1.34 | 9.60±1.79 | 9.29±1.21 | –0.08±1.26 | –0.41±1.59 | 0.680 |
LV mass, g | 92.00±19.60 | 90.80±16.60 | 94.70±20.20 | 95.30±16.70 | –1.03±13.50 | 0.27±11.50 | 0.615 |
LVEF, % | 62.20±9.90 | 62.20±6.56 | 64.30±5.10 | 64.30±5.37 | 0.33±9.42 | –0.15±5.19 | 0.970 |
E/A | 0.86±0.20 | 0.87±0.20 | 0.98±0.32 | 0.96±0.31 | –0.02±0.18 | –0.03±0.21 | 0.562 |
DT, ms | 208.2±43.3 | 238.0±28.9a | 213.6±41.4 | 238.0±47.5b | 29.9±45.7 | 24.4±49.0 | 0.687 |
Septal e’, m/s | 0.0744±0.02 | 0.0744±0.02 | 0.0680±0.02 | 0.0676±0.02 | 0.0004±0.02 | –0.0007±0.01 | 0.928 |
Lateral e’, m/s | 0.094±0.02 | 0.099±0.02 | 0.097±0.02 | 0.094±0.03 | 0.007±0.01 | –0.005±0.02 | 0.093 |
Average E/e’ | 10.20±2.64 | 9.68±2.77c | 11.60±2.52 | 11.30±2.67c | –0.55±1.81 | –0.22±2.36 | 0.583 |
LAVi, mL/m2 | 31.50±7.50 | 30.60±8.27 | 32.20±8.75 | 33.60±12.40 | –0.46±7.24 | 1.07±11.50 | 0.394 |
Values are presented as percent, mean±standard deviation, or median (interquartile range). Albuminuria status was assessed with a random urine sample, and categorized according to urine albumin to creatinine ratio (A1: <30 mg/g; A2: ≥30–<300 mg/g; A3 ≥300 mg/g). BMI, body mass index; WC, waist circumference; BP, blood pressure; HbA1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; CEC, cholesterol efflux capacity; LDL-C, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; FFA, free fatty acid; BHB, β-hydroxybutyrate; hsCRP, high sensitivity C-reactive protein; VCTE, vibration-controlled transient elastography; CAP, controlled attenuation parameter; LS, liver stiffness; STDR, sight threatening diabetic retinopathy; ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin II receptor blocker. Log-transformed before analysis.
Values are presented as median (interquartile range) or mean±standard deviation. BHB, β-hydroxybutyrate; WC, waist circumference; BP, blood pressure; FG, fasting glucose; HbA1c, glycosylated hemoglobin; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAP, controlled attenuation parameter; LS, liver stiffness; CEC, cholesterol efflux capacity; hsCRP, high sensitivity C-reactive protein; FFA, free fatty acid. Log-transformed before analysis, Sex-adjusted <0.05, <0.01, <0.001 vs. baseline.
BHB, β-hydroxybutyrate; BP, blood pressure; HbA1c, glycosylated hemoglobin; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; CEC, cholesterol efflux capacity; ALT, alanine aminotransferase; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; CAP, controlled attenuation parameter; LS, liver stiffness; FFA, free fatty acid; hsCRP, high sensitivity C-reactive protein. Log-transformed before analysis.
Values are presented as mean±standard deviation. IVSd, inter-ventricular septal dimension; LVPWd, left ventricular posterior wall thickness at end-diastole; LV, left ventricular; LVEF, left ventricular ejection fraction; E wave, peak trans-mitral flow velocities in early diastole; A wave, peak trans-mitral flow velocities in late diastole; DT, deceleration time; e’, peak velocities of septal and lateral mitral annulus in early diastole; LAVi, left atrial volume divided by body surface area of the participants. Paired