Baseline characteristics
A total of 4,007 patients with T2DM receiving insulin therapy were initially screened. Among those, 623 patients who underwent ≥2 CCTAs were finally included in the study analysis. The mean age was 63.0 (±10.1) years, and 379 (60.8%) of them were male. Between the two CCTA examinations, a DPP-4i was prescribed to 380 patients, and it was not prescribed to 243 patients. The DPP-4i and no DPP-4i groups did not differ significantly in age or body mass index (Table 1). HbA1c level was significantly higher in the DPP-4i group at baseline (8.5 ± 2.1% vs. 8.1 ± 2.2% in the DPP-4i group and no DPP-4i group, respectively, p=0.009) and was similar in the two groups at follow-up (7.9 ± 1.7 vs. 7.8 ± 2.0, p=0.465). Among the baseline comorbidities, prior MI and atrial fibrillation were more prevalent in the no DPP-4i group. More patients in the no DPP-4i group received CABG before the CCTAs (14.7% vs. 31.7%, p <0.001). The prescription rate for a beta-blocker was lower in the DPP-4i group, and the prescription rates for metformin and sulfonylurea were higher in the DPP-4i group. After the PS-matching procedure, 220 patients remained in each group. The baseline demographic characteristics, comorbidities, and prescription rates of concurrent medications were well-balanced in the two groups after PS-matching (Table 2).
Table 1. Baseline characteristics in the two groups before PS matching
Variable
|
DPP-4i (N=380)
|
No DPP-4i (N=243)
|
p
|
Age, years
|
63.1 ± 10.3
|
62.8 ± 9.8
|
0.690
|
Male, n (%)
|
219 (57.6%)
|
160 (65.8%)
|
0.050
|
Body mass index
|
25.1 ± 3.6
|
25.2 ± 4.2
|
0.815
|
HbA1c at baseline
|
8.5 ± 2.1
|
8.1 ± 2.2
|
0.009
|
HbA1c at follow-up
|
7.9 ± 1.7
|
7.8 ± 2.0
|
0.465
|
Mean HbA1c, %
|
8.2 ± 1.4
|
7.9 ± 1.8
|
0.039
|
Mean SBP, mmHg
|
133 ± 17
|
135 ± 17
|
0.191
|
Mean DBP, mmHg
|
68 ± 10
|
66 ± 9
|
0.015
|
Hypertension
|
288 (75.8%)
|
189 (77.8%)
|
0.635
|
Heart failure
|
127 (33.4%)
|
88 (36.2%)
|
0.529
|
Chronic kidney disease
|
92 (24.2%)
|
59 (24.3%)
|
1.000
|
Prior MI
|
41 (10.8%)
|
42 (17.3%)
|
0.027
|
PAOD
|
90 (23.7%)
|
49 (20.2%)
|
0.352
|
Atrial fibrillation
|
29 (7.6%)
|
37 (15.2%)
|
0.004
|
Stroke
|
88 (23.2%)
|
44 (18.1%)
|
0.160
|
Dyslipidemia
|
359 (94.5%)
|
221 (90.9%)
|
0.126
|
Prior PCI
|
78 (20.5%)
|
62 (25.5%)
|
0.175
|
Prior CABG
|
56 (14.7%)
|
77 (31.7%)
|
<0.001
|
Medications
|
|
|
|
Antiplatelet agent
|
243 (63.9%)
|
172 (70.8%)
|
0.093
|
RAS-blocker
|
191 (50.3%)
|
132 (54.3%)
|
0.365
|
Beta-blocker
|
169 (44.5%)
|
129 (53.1%)
|
0.044
|
Statin
|
301 (79.2%)
|
194 (79.8%)
|
0.931
|
Metformin
|
350 (92.1%)
|
191 (78.6%)
|
<0.001
|
Sulfonylurea
|
285 (75.0%)
|
135 (55.6%)
|
<0.001
|
Thiazolidinedione
|
55 (14.5%)
|
25 (10.3%)
|
0.161
|
SGLT-2 inhibitor
|
55 (14.5%)
|
38 (15.6%)
|
0.778
|
PS = propensity score; DPP-4i = dipeptidyl peptidase-4 inhibitor; SBP = systolic blood pressure; DBP = diastolic blood pressure; MI = myocardial infarction; PAOD = peripheral arterial occlusive disease; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; RAS = renin-angiotensin system; SGLT = sodium-glucose linked transporter
Table 2. Baseline characteristics in PS-matched patients
Variable
|
DPP-4i (N=220)
|
No DPP-4i(N=220)
|
p
|
Age, years
|
63.1 ± 9.7
|
62.8 ± 9.9
|
0.696
|
Male, n (%)
|
131 (59.5%)
|
146 (66.4%)
|
0.167
|
Body mass index
|
24.8 ± 3.4
|
25.2 ± 4.2
|
0.300
|
HbA1c at baseline
|
8.3 ± 1.9
|
8.1 ± 2.2
|
0.368
|
HbA1c at follow-up
|
7.8 ± 1.6
|
7.8 ± 2.0
|
0.951
|
Mean HbA1c, %
|
8.1 ± 1.3
|
8.0 ± 1.8
|
0.613
|
Mean SBP, mmHg
|
133 ± 17
|
134 ± 16
|
0.542
|
Mean DBP, mmHg
|
67 ± 10
|
66 ± 9
|
0.267
|
Hypertension
|
168 (76.4%)
|
169 (76.8%)
|
1.000
|
Heart failure
|
77 (35.0%)
|
74 (33.6%)
|
0.841
|
Chronic kidney disease
|
57 (25.9%)
|
53 (24.6%)
|
0.741
|
Prior MI
|
26 (11.8%)
|
33 (15.0%)
|
0.401
|
PAOD
|
50 (22.7%)
|
46 (20.9%)
|
0.729
|
Atrial fibrillation
|
21 (9.5%)
|
29 (13.2%)
|
0.293
|
Stroke
|
54 (24.5%)
|
39 (17.7%)
|
0.102
|
Dyslipidemia
|
215 (95.5%)
|
200 (90.9%)
|
0.089
|
Prior PCI
|
45 (20.5%)
|
57 (25.9%)
|
0.214
|
Prior CABG
|
56 (25.5%)
|
54 (24.5%)
|
0.912
|
Medications
|
|
|
|
Antiplatelet agent
|
149 (67.7%)
|
151 (68.6%)
|
0.918
|
RAS-blocker
|
107 (48.6%)
|
121 (55.0%)
|
0.215
|
Beta-blocker
|
101 (45.9%)
|
113 (51.4%)
|
0.294
|
Statin
|
174 (79.1%)
|
177 (80.5%)
|
0.812
|
Metformin
|
191 (86.8%)
|
186 (84.5%)
|
0.586
|
Sulfonylurea
|
144 (65.5%)
|
128 (58.2%)
|
0.141
|
Thiazolidinedione
|
28 (12.7%)
|
24 (10.9%)
|
0.658
|
SGLT-2 inhibitor
|
30 (13.6%)
|
38 (17.3%)
|
0.356
|
Abbreviations are same as Table 1.
Outcomes before PS-matching
The median time difference between the two CCTAs was 39.0 (17.0–61.4) months. The prevalence of OCAD on CCTA was 32.9% vs. 53.5% (p<0.001) in the DPP-4i group and no DPP-4i group, respectively, at baseline and changed to 36.6% vs. 64.6% at follow-up (p<0.001) (Table 3). New OCAD was detected on the follow-up CCTA in 62 (16.3%) patients in the DPP-4i group and 76 (31.3%) patients in the no DPP-4i group (p<0.001). The new PCI rate during the interval was similar in the two groups (7.4% vs. 7.0%, p=0.969), but the new CABG rate during the interval was significantly higher in the no DPP-4i group (2.6% vs. 7.8% in the DPP-4i group and no DPP-4i group, respectively, p=0.005). The composite rate of new OCAD or new revascularization was significantly lower in the DPP-4i group (19.7% vs. 38.7%, p<0.001). The result was consistent after excluding patients who have undergone CABG at baseline. CCS data were available at both the baseline and follow-up CCTA in 265 patients in the DPP-4i group and 115 patients in the no DPP-4i group. The median change in CCS per year was 13.3 (0.1 – 56.8) vs. 13.5 (0.0 – 78.6) in the DPP-4i and no DPP-4i group, respectively (p=0.793).
Table 3. Outcomes in the two groups before PS-matching.
Variable
|
DPP-4i (N=380)
|
No DPP-4i (N=243)
|
p
|
OCAD analysis, n(%)
|
|
|
|
OCAD (baseline)
|
125 (32.9%)
|
130 (53.5%)
|
<0.001
|
OCAD (follow-up)
|
139 (36.6%)
|
157 (64.6%)
|
<0.001
|
New OCAD at follow-up
|
62 (16.3%)
|
76 (31.3%)
|
<0.001
|
New PCI during follow-up, n(%)
|
28 (7.4%)
|
17 (7.0%)
|
0.969
|
New CABG during follow-up, n(%)
|
10 (2.6%)
|
19 (7.8%)
|
0.005
|
New OCAD or revascularization, n(%)
|
75 (19.7%)
|
94 (38.7%)
|
<0.001
|
New OCAD or revascularization, after excluding patients with prior CABG, n(%)
|
55/324 (17.0%)
|
56/166 (33.7%)
|
<0.001
|
CCS analysis*
|
|
|
|
CCS (baseline)
|
39.5 (0.6 – 247.8)
|
60.5 (0.2 – 268.1)
|
0.630
|
CCS (follow-up)
|
105.5 (8.4 – 507.7)
|
137.9 (17.2 – 554.8)
|
0.362
|
CCS change/year
|
13.3 (0.1 – 56.8)
|
13.5 (0.0 – 78.6)
|
0.793
|
*CCS data was analyzed in 380 patients, including 265 patients in the DPP-4i group and 115 patients in the no DPP-4i group.
PS = propensity score; DPP-4i = dipeptidyl peptidase-4 inhibitor; OCAD = obstructive coronary artery disease; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; CCS = coronary calcium score;
Outcomes in the PS-matched population
In the PS-matched cohort, the prevalence of OCAD on the baseline CCTA was 41.8% vs. 48.6% (p=0.180), and changed to 46.4% vs. 60.9% (p=0.003) at follow-up in the DPP-4i and no DPP-4i groups, respectively (Table 4). New OCAD was detected on the follow-up CCTA in 35 (15.9%) patients in the DPP-4i group and 65 (29.5%) patients in the no DPP-4i group (p=0.001). The new PCI rate during the interval was non-significantly higher in the no DPP-4i group (5.9% vs. 7.7% in the DPP-4i group and no DPP-4i group, respectively, p=0.570), and the new CABG rate during the interval was significantly higher in the no DPP-4i group (2.3% vs. 8.2% in the DPP-4i group and no DPP-4i group, respectively, p=0.010). The composite rate of new OCAD or new revascularization was significantly lower in the DPP-4i group (18.6% vs. 37.3%, p<0.001). The incidence of new OCAD or new revascularization was also lower in the DPP-4i group after excluding patients who had undergone CABG (18.6% vs. 37.3%, p<0.001). CCS data were available in 138 patients in the DPP-4i group and 115 patients in the no DPP-4i group. The median CCS change per year was 9.1 (0.1 – 56.8) in the DPP-4i group and 13.5 (0.0 – 78.6) in the no DPP-4i group (p=0.715). In subgroup analyses, the benefit of DPP-4is on the progression of OCAD in patients with T2DM receiving insulin therapy were consistent across all prespecified subgroups except in patients with age <65 years (Figure 1). Also there was a trend favoring DPP-4is in patients with female sex or higher baseline HbA1c level.
Table 4. Outcomes in the PS-matched population
Variable
|
DPP-4i (N=220)
|
No DPP-4i (N=220)
|
p
|
OCAD analysis, n (%)
|
|
|
|
OCAD (baseline)
|
92 (41.8%)
|
107 (48.6%)
|
0.180
|
OCAD (follow-up)
|
102 (46.4%)
|
134 (60.9%)
|
0.003
|
New OCAD at follow-up
|
35 (15.9%)
|
65 (29.5%)
|
0.001
|
New PCI during follow-up, n(%)
|
13 (5.9%)
|
17 (7.7%)
|
0.570
|
New CABG during follow-up, n(%)
|
5 (2.3%)
|
18 (8.2%)
|
0.010
|
New OCAD or revascularization, n(%)
|
41 (18.6%)
|
82 (37.3%)
|
<0.001
|
New OCAD or revascularization, after excluding patients with prior CABG, n(%)
|
34/164 (20.7%)
|
66/166 (39.8%)
|
<0.001
|
CCS analysis*
|
|
|
|
CCS (baseline)
|
28.9 (0.1 – 231.6)
|
60.5 (0.2 – 268.1)
|
0.247
|
CCS (follow-up)
|
70.2 (2.7 – 454.5)
|
137.9 (17.2 – 554.8)
|
0.078
|
CCS change/year
|
9.1 (0.1 – 56.8)
|
13.5 (0.0 – 78.6)
|
0.715
|
*CCS data was analyzed in 253 patients, including 138 patients in the DPP-4i group and 115 patients in the no DPP-4i group.
Abbreviations are same as Table 3.