Introduction
Methods
Study Population
Compliance with Ethical Guidelines
Measurement of Carotid IMT
Statistical Analysis
Results
Results from the Original SPIKE Study
Baseline Characteristics
Parameters | Conventional treatment group | Lower sitagliptin dose group (<50 mg/day) | Higher sitagliptin dose group (≥50 mg/day) |
P value (intergroup) |
---|---|---|---|---|
Age (years) | 63.6 ± 10.0 (n = 137) | 65.3 ± 9.9 (n = 42) | 63.2 ± 9.6 (n = 95) | 0.51 |
Male gender | 82 (59.9%) | 27 (64.3%) | 56 (58.9%) | 0.84 |
Duration of diabetes (years) | 17.3 ± 8.7 (n = 134) | 17.6 ± 8.7 (n = 41) | 17.1 ± 8.4 (n = 94) | 0.96 |
Body mass index (kg/m2) | 25.1 ± 3.4 (n = 137) | 24.6 ± 4.2 (n = 42) | 25.2 ± 4.4 (n = 95) | 0.74 |
HbA1c (%) | 8.0 ± 1.0 (n = 137) | 7.7 ± 0.8 (n = 42) | 8.3 ± 1.1 (n = 95) | 0.002 |
HbA1c (mmol/mol) | 63.9 ± 10.6 (n = 137) | 60.0 ± 8.8 (n = 42) | 67.1 ± 12.5 (n = 95) | 0.002 |
Total cholesterol (mmol/l) | 4.94 ± 0.86 (n = 137) | 4.86 ± 0.73 (n = 41) | 5.08 ± 0.98 (n = 95) | 0.32 |
LDL cholesterol (mmol/l) | 2.78 ± 0.70 (n = 136) | 2.84 ± 0.58 (n = 42) | 2.85 ± 0.85 (n = 95) | 0.74 |
HDL cholesterol (mmol/l) | 1.39 ± 0.38 (n = 136) | 1.41 ± 0.40 (n = 42) | 1.48 ± 0.36 (n = 95) | 0.23 |
Triglycerides (mmol/l) | 1.17 (0.90, 1.72) (n = 137) | 1.16 (0.89, 1.40) (n = 42) | 1.11 (0.79, 1.67) (n = 94) | 0.76 |
Systolic BP (mmHg) | 132.0 ± 14.3 (n = 137) | 130.6 ± 16.5 (n = 42) | 130.0 ± 15.5 (n = 95) | 0.60 |
Diastolic BP (mmHg) | 74.7 ± 12.0 (n = 137) | 76.8 ± 10.9 (n = 42) | 74.3 ± 11.1 (n = 95) | 0.48 |
eGFR (ml/min/1.73 m2) | 79.7 ± 24.2 (n = 137) | 75.4 ± 17.9 (n = 42) | 78.7 ± 22.5 (n = 95) | 0.56 |
UAE (mg/g creatinine) | 108.9 ± 224.3 (n = 134) | 83.4 ± 173.9 (n = 42) | 226.6 ± 666.6 (n = 94) | 0.08 |
Number of insulin injections (times/day) | 2.9 ± 1.2 (n = 137) | 3.1 ± 1.0 (n = 42) | 2.8 ± 1.2 (n = 95) | 0.64 |
Metformin | 48 (35.0) | 13 (31.0) | 36 (37.9) | 0.73 |
Sulfonylurea | 15 (10.9) | 13 (31.0) | 4 (4.2) | <0.001 |
Glinide | 19 (13.9) | 0 (0) | 2 (2.1) | <0.001 |
Thiazolidinedione | 11 (8.0) | 4 (9.5) | 9 (9.5) | 0.88 |
α-Glucosidase inhibitor | 42 (30.7) | 11 (26.2) | 30 (31.6) | 0.82 |
Angiotensin-converting enzyme inhibitor | 4 (2.9) | 3 (7.1) | 5 (5.3) | 0.40 |
Angiotensin II receptor blocker | 69 (50.4) | 17 (40.5) | 36 (37.9) | 0.15 |
Statin | 63 (46.0) | 21 (50.0) | 45 (47.4) | 0.89 |
Antiplatelet agent | 30 (21.9) | 12 (28.6) | 17 (17.9) | 0.36 |
Changes in Clinical Parameters in the Three Groups
Parameters | Conventional treatment group | Lower sitagliptin dose group | Higher sitagliptin dose group |
P value (intergroup) |
---|---|---|---|---|
Body mass index (kg/m2) | 0.12 ± 1.77 (n = 117) | 0.04 ± 1.15 (n = 37) | 0.08 ± 1.62 (n = 82) | 0.96 |
HbA1c (%) | −0.20 ± 0.91 (n = 122)* | −0.25 ± 0.97 (n = 37) | −0.62 ± 1.05 (n = 84)§
| 0.008 |
HbA1c (mmol/mol) | −2.23 ± 9.99 (n = 122)* | −2.72 ± 10.61 (n = 37) | −6.82 ± 11.52 (n = 84)§
| 0.008 |
Total cholesterol (%) | −1.79 ± 14.60 (n = 122) | 1.16 ± 13.55 (n = 37) | −4.44 ± 16.16 (n = 84)* | 0.15 |
LDL cholesterol (%) | 5.18 ± 23.93 (n = 121)* | 3.39 ± 23.90 (n = 38) | −0.20 ± 23.29 (n = 84) | 0.28 |
HDL cholesterol (%) | −0.46 ± 14.72 (n = 121) | 4.53 ± 16.21 (n = 37) | −1.74 ± 14.49 (n = 84) | 0.10 |
Triglycerides (%) | −1.58 (−24.57, 16.67) (n = 122) | −1.89 (−28.57, 49.06) (n = 37) | 0.00 (−24.22, 43.75) (n = 83)* | 0.29 |
Systolic BP (mmHg) | 2.52 ± 16.75 (n = 122) | 1.83 ± 18.71 (n = 36) | −1.45 ± 19.11 (n = 83) | 0.29 |
Diastolic BP (mmHg) | 2.19 ± 13.15 (n = 122) | −1.00 ± 12.94 (n = 36) | 0.42 ± 10.05 (n = 83) | 0.32 |
eGFR (ml/min/1.73 m2) | −2.65 ± 11.76 (n = 122)* | −4.56 ± 8.69 (n = 36)#
| −3.70 ± 11.00 (n = 84)#
| 0.61 |
UAE (mg/g creatinine) | 23.9 ± 249.6 (n = 114) | 63.2 ± 222.3 (n = 35) | −18.9 ± 356.4 (n = 79) | 0.34 |
Frequency of hypoglycemic events (episodes/month/person) | 0.36 ± 0.80 | 0.67 ± 1.28 | 0.20 ± 0.52 | 0.008 |
Changes in IMT-CCA Among the Three Groups
Parameter | Conventional treatment group | Lower sitagliptin dose group | Higher sitagliptin dose group |
P value (intergroup) |
---|---|---|---|---|
Mean IMT-CCA (mm) | ||||
Baseline (mm) | 0.84 ± 0.21 (n = 137) | 0.82 ± 0.21 (n = 42) | 0.85 ± 0.17 (n = 95) | 0.69 |
104 weeks (mm) | 0.86 ± 0.24 (n = 122) | 0.83 ± 0.24 (n = 38) | 0.81 ± 0.17 (n = 83) | 0.16 |
P value (intragroup) | 0.06 | 0.61 | 0.001 | |
Right maximum IMT-CCA (mm) | ||||
Baseline (mm) | 1.06 ± 0.40 (n = 137) | 1.05 ± 0.30 (n = 41) | 1.04 ± 0.28 (n = 95) | 0.91 |
104 week (mm) | 1.09 ± 0.49 (n = 122) | 1.11 ± 0.41 (n = 38) | 1.00 ± 0.30 (n = 83) | 0.26 |
P value (intragroup) | 0.51 | 0.44 | 0.51 | |
Left maximum IMT-CCA (mm) | ||||
Baseline (mm) | 1.11 ± 0.41 (n = 137) | 1.06 ± 0.34 (n = 42) | 1.12 ± 0.32 (n = 95) | 0.64 |
104 week (mm) | 1.12 ± 0.42 (n = 122) | 1.04 ± 0.32 (n = 38) | 1.03 ± 0.29 (n = 83) | 0.19 |
P value (intragroup) | 0.39 | 0.88 | 0.010 |
Parameters | Treatment effect (mm) |
P value by ANCOVA |
P value by Tukey-Kramer |
---|---|---|---|
Mean IMT-CCA (mm) | |||
Conventional treatment group vs. lower sitagliptin dose group | −0.02 (−0.08, 0.05) | 0.006 | 0.82 |
Conventional treatment group vs. higher sitagliptin dose group | −0.07 (−0.12, −0.02) | 0.004 | |
Lower sitagliptin dose group vs. higher sitagliptin dose group | −0.05 (−0.12, 0.02) | 0.19 | |
Right maximum IMT-CCA (mm) | |||
Conventional treatment group vs. lower sitagliptin dose group | 0.02 (−0.13, 0.17) | 0.43 | 0.95 |
Conventional treatment group vs. higher sitagliptin dose group | −0.05 (−0.17, 0.06) | 0.51 | |
Lower sitagliptin dose group vs. higher sitagliptin dose group | −0.08 (−0.24, 0.09) | 0.52 | |
Left maximum IMT-CCA (mm) | |||
Conventional treatment group vs. lower sitagliptin dose group | −0.06 (−0.19, 0.07) | 0.06 | 0.51 |
Conventional treatment group vs. higher sitagliptin dose group | −0.10 (−0.19, 0.00) | 0.05 | |
Lower sitagliptin dose group vs. higher sitagliptin dose group | −0.04 (−0.17, 0.10) | 0.79 |
Variable | Regression coefficient (SE) |
P value |
---|---|---|
Change in mean IMT-CCA | ||
Model 1 | −0.0015 (0.0004) | <0.001 |
Model 2 | −0.0013 (0.0004) | 0.002 |
Model 3 | −0.0014 (0.0004) | <0.001 |
Model 4 | −0.0014 (0.0004) | 0.002 |
Change in right max IMT-CCA | ||
Model 1 | −0.0008 (0.0010) | 0.42 |
Model 2 | −0.0010 (0.0010) | 0.29 |
Model 3 | −0.0013 (0.0010) | 0.20 |
Model 4 | −0.0012 (0.0010) | 0.25 |
Change in left max IMT-CCA | ||
Model 1 | −0.0022 (0.0009) | 0.014 |
Model 2 | −0.0019 (0.0008) | 0.018 |
Model 3 | −0.0023 (0.0008) | 0.006 |
Model 4 | −0.0023 (0.0009) | 0.008 |
Variable | Regression coefficient (SE) |
P value |
---|---|---|
Change in mean IMT-CCA | ||
Model 1 | −0.0010 (0.0003) | 0.003 |
Model 2 | −0.0008 (0.0003) | 0.009 |
Model 3 | −0.0009 (0.0003) | 0.006 |
Model 4 | −0.0008 (0.0003) | 0.010 |
Change in right max IMT-CCA | ||
Model 1 | −0.0001 (0.0008) | 0.92 |
Model 2 | −0.0002 (0.0007) | 0.78 |
Model 3 | −0.0003 (0.0008) | 0.65 |
Model 4 | −0.0002 (0.0008) | 0.75 |
Change in left max IMT-CCA | ||
Model 1 | −0.0013 (0.0007) | 0.046 |
Model 2 | −0.0012 (0.0006) | 0.06 |
Model 3 | −0.0014 (0.0006) | 0.022 |
Model 4 | −0.0014 (0.0006) | 0.030 |