Introduction
Methods
Study design
Participants
Intervention
Outcome measures
Statistical analysis
Results
Participants
Characteristic | Placebo (n = 21) | OM-3CA (n = 20) | Dapagliflozin (n = 21) | OM-3CA + dapagliflozin (n = 22) | Total (N = 84) |
---|---|---|---|---|---|
Age, years | 65.6 (6.1) | 66.2 (5.9) | 65.0 (6.5) | 65.0 (5.4) | 65.5 (5.9) |
Sex, male/female, n/n | 17/4 | 11/9 | 16/5 | 15/7 | 59/25 |
Weight, kg | 93.0 (12.2) | 95.6 (13.7) | 90.2 (8.7) | 91.7 (12.9) | 92.6 (12.0) |
BMI, kg/m2 | 30.3 (3.1) | 33.0 (4.1) | 30.5 (2.8) | 31.1 (3.6) | 31.2 (3.5) |
Overweight/obesea, n/n | 10/11 | 5/15 | 11/10 | 10/12 | 36/48 |
Diabetes duration, years | 6.5 (4.2) | 6.3 (5.1) | 6.7 (6.0) | 8.5 (4.5) | 7.0 (5.0) |
Liver fat content
Variable | Placebo (n = 19) | OM-3CA (n = 15) | Dapagliflozin (n = 19) | OM-3CA + dapagliflozin (n = 20) |
---|---|---|---|---|
Body weight, kg | ||||
Baseline | 92.9 (12.16) | 95.6 (13.68) | 90.3 (9.04) | 91.6 (12.84) |
Change | −0.27 (1.79) | −0.16 (1.02) | −2.44 (2.14) | −2.16 (1.30) |
GMR | 1.00 (0.99, 0.01) | 1.00 (0.99, 1.00) | 0.97 (0.96, 0.98)* | 0.98 (0.97, 0.98)* |
Waist circumference, cm | ||||
Baseline | 109.9 (7.4) | 114.5 (9.7) | 110.1 (8.5) | 110.7 (8.7) |
Change | 0.9 (3.6) | 0.1 (2.2) | −2.2 (3.3) | −2.2 (3.2) |
GMR | 1.01 (0.99, 1.02) | 1.00 (0.99, 1.01) | 0.98 (0.97, 1.00)* | 0.98 (0.97, 0.99)* |
Hip circumference, cm | ||||
Baseline | 107.5 (7.8) | 112.6 (9.4) | 106.2 (6.8) | 107.5 (7.3) |
Change | 0.3 (4.4) | −0.6 (3.8) | −2.3 (4.2) | −0.4 (4.2) |
GMR | 1.00 (0.98, 1.02) | 0.99 (0.97, 1.01) | 0.98 (0.96, 1.00)* | 1.00 (0.98, 1.01) |
Liver PDFF, % | ||||
Baseline | 15.1 (6.5) | 22.2 (11.0) | 17.3 (9.1) | 17.8 (9.2) |
Change | −0.59 (1.86) | −3.15 (2.88) | −2.23 (3.30) | −3.15 (3.49) |
GMR | 0.97 (0.90, 1.04) | 0.85 (0.78, 0.92) | 0.87 (0.77, 0.99) | 0.79 (0.69, 0.90)* |
Total liver volume, l | ||||
Baseline | 1.91 (0.35) | 2.30 (0.70) | 1.88 (0.44) | 1.88 (0.51) |
Change | −0.001 (0.120) | −0.025 (0.165) | −0.049 (0.153) | −0.060 (0.129) |
GMR | 1.00 (0.97, 1.03) | 0.99 (0.95, 1.04) | 0.98 (0.94, 1.01) | 0.97 (0.94, 1.00) |
Total liver fat volume, l | ||||
Baseline | 0.30 (0.17) | 0.51 (0.37) | 0.37 (0.28) | 0.36 (0.25) |
Change | −0.01 (0.04) | −0.07 (0.11) | −0.06 (0.09) | −0.07 (0.08) |
GMR | 0.97 (0.88, 1.06) | 0.84 (0.75, 0.94) | 0.85 (0.74, 0.98) | 0.76 (0.65, 0.89)* |
Subcutaneous adipose tissue volume, l | ||||
Baseline | 3.91 (1.59) | 4.93 (2.03) | 3.84 (1.40) | 4.10 (1.53) |
Change | −0.06 (0.22) | 0.05 (0.13) | −0.29 (0.28) | −0.23 (0.22) |
GMR | 0.98 (0.95, 1.01) | 1.01 (0.99, 1.04) | 0.92 (0.90, 0.95)* | 0.94 (0.91, 0.96)* |
Visceral adipose tissue volume, l | ||||
Baseline | 3.96 (1.06) | 4.32 (1.20) | 4.02 (1.03) | 3.95 (1.02) |
Change | 0.03 (0.32) | 0.01 (0.20) | −0.27 (0.25) | −0.17 (0.23) |
GMR | 1.01 (0.97, 1.05) | 1.00 (0.98, 1.03) | 0.93 (0.90, 0.96)* | 0.96 (0.93, 0.99)* |
Anthropometrics and abdominal adipose tissue volumes
Glucose metabolism
Variable | Placebo (n = 20) | OM-3CA (n = 14) | Dapagliflozin (n = 20) | OM-3CA + dapagliflozin (n = 19) |
---|---|---|---|---|
HbA1ca | ||||
Baseline, mmol/mol | 57.9 (9.0) | 57.3 (8.4) | 56.7 (6.1) | 58.9 (8.9) |
Baseline, % | 7.44 (0.80) | 7.38 (0.68) | 7.38 (0.56) | 7.50 (0.76) |
Change, mmol/mol | −0.99 (3.81) | 1.43 (4.35) | −6.89 (7.24) | −4.88 (5.25) |
Change, % units | −0.09 (0.35) | 0.13 (0.40) | −0.63 (0.66) | −0.45 (0.48) |
GMR | 0.99 (0.97, 1.01) | 1.01 (0.98, 1.04) | 0.91 (0.87, 0.96)* | 0.94 (0.92, 0.97) |
Fasting glucose, mmol/l | ||||
Baseline | 9.40 (1.65) | 9.02 (1.48) | 8.99 (1.85) | 9.38 (1.97) |
Change | 0.37 (0.82) | 0.21 (1.07) | −0.98 (1.49) | −0.91 (2.00) |
GMR | 1.04 (0.99, 1.08) | 1.02 (0.95, 1.09) | 0.90 (0.84, 0.96)* | 0.91 (0.83, 1.01)* |
Fasting insulin, pmol/l | ||||
Baseline | 72.5 (40.0) | 94.9 (39.2) | 79.1 (38.5) | 75.2 (28.3) |
Change | −3.8 (18.3) | −4.0 (15.8) | −9.6 (24.6) | −10.7 (22.6) |
GMR | 0.94 (0.82, 1.07) | 0.96 (0.84, 1.09) | 0.84 (0.72, 0.98) | 0.81 (0.71, 0.93) |
HOMA-IRb | ||||
Baseline | 4.2 (2.4) | 5.4 (2.9) | 4.3(1.9) | 4.4 (1.7) |
Change | −0.19 (1.44) | 0.31 (2.39) | −1.08 (1.38) | −0.86 (1.58) |
GMR | 0.97 (0.84, 1.12) | 1.03 (0.83, 1.28) | 0.72 (0.60, 0.86)* | 0.76 (0.65, 0.90)* |
120 min glucosec, mmol/l | ||||
Baseline | 17.5 (3.8) | 16.9 (2.2) | 17.2 (4.1) | 16.8 (3.8) |
Change | 0.7 (1.9) | 0.4 (0.8) | −2.2 (3.1) | −1.2 (2.2) |
GMR | 1.06 (0.99, 1.12) | 1.02 (0.99, 1.06) | 0.88 (0.78, 0.98)* | 0.94 (0.88, 1.01)* |
NEFA, mmol/l | ||||
Baseline | 0.76 (0.34) | 0.64 (0.16) | 0.64 (0.20) | 0.66 (0.18) |
Change | −0.08 (0.18) | 0.02 (0.14) | 0.04 (0.18) | 0.02 (0.17) |
GMR | 0.91 (0.80, 1.03) | 1.00 (0.84, 1.20) | 1.07 (0.92, 1.23) | 1.03 (0.90, 1.18) |
Insulin sensitivity index for lipolysisd | ||||
Baseline | 0.79 (0.261) | 0.64 (0.238) | 0.79 (0.260) | 0.79 (0.251) |
Change | 0.027 (0.123) | 0.010 (0.171) | −0.022 (0.124) | 0.027 (0.149) |
GMR | 1.04 (0.96, 1.13) | 1.04 (0.90, 1.19) | 0.99 (0.90, 1.08) | 1.05 (0.94, 1.16) |
Plasma fatty acid composition and lipoprotein levels
Variable | Placebo (n = 20) | OM-3CA (n = 16) | Dapagliflozin (n = 19) | OM-3CA + dapagliflozin (n = 20) |
---|---|---|---|---|
20:4 n-6/20:3 n-6 (δ-5 desaturase) | ||||
Baseline | 9.87 (2.42) | 9.14 (2.37) | 8.76 (1.98) | 10.91 (1.97) |
Change | 0.26 (0.82) | 3.53 (2.57) | 1.24 (1.50) | 3.79 (3.10) |
GMR | 1.02 (0.98, 1.06) | 1.38 (1.22, 1.55)* | 1.14 (1.07, 1.21) | 1.33 (1.20, 1.47)* |
18:3 n-6/18:2 n-6 (δ-6 desaturase) | ||||
Baseline | 0.022 (0.01) | 0.025 (0.008) | 0.021 (0.009) | 0.023 (0.009) |
Change | −0.002 (0.006) | −0.009 (0.006) | −0.001 (0.009) | −0.008 (0.006) |
GMR | 0.94 (0.85, 1.04) | 0.66 (0.58, 0.76)* | 0.95 (0.79, 1.15) | 0.65 (0.56, 0.74)* |
16:1 n-7/16:0 (δ-9 desaturase) | ||||
Baseline | 0.301 (0.112) | 0.343 (0.089) | 0.314 (0.131) | 0.279 (0.080) |
Change | −0.016 (0.047) | −0.070 (0.052) | −0.027 (0.086) | −0.072 (0.053) |
GMR | 0.96 (0.88, 1.03) | 0.78 (0.72, 0.85)* | 0.93 (0.82, 1.05) | 0.74 (0.68, 0.80)* |
18:1 n-9/18:0 (δ-9 desaturase) | ||||
Baseline | 30.7 (7.39) | 29.2 (4.44) | 30.7 (7.48) | 32.0 (5.99) |
Change | 1.21 (5.34) | −1.29 (6.27) | 1.97 (7.13) | −3.79 (7.34) |
GMR | 1.04 (0.96, 1.14) | 0.95 (0.84, 1.08) | 1.09 (0.96, 1.23) | 0.88 (0.78, 1.00) |