| |
Time at risk (person-years)
|
Incidence rate (per 1000 person-years)
|
Unadjusted HR (95 % CI)
|
Adjusted HR* (95 % CI)
|
p value
|
|---|
|
MACEs
|
|
Antidiabetic drug (ref. = DPP4i)
|
28,508
|
39.56
|
–
|
–
|
–
|
|
No antidiabetic drug
|
101,166
|
62.02
|
1.52 (1.39, 1.65)
|
1.31 (1.20, 1.43)
|
<0.0001
|
|
Sulfonylureas
|
110,618
|
35.99
|
0.89 (0.81, 0.96)
|
0.96 (0.88, 1.05)
|
0.3942
|
|
Acarbose
|
22,800
|
48.37
|
1.20 (1.08, 1.33)
|
1.07 (0.96, 1.18)
|
0.2098
|
|
Meglitinides
|
13,103
|
102.49
|
2.52 (2.27, 2.78)
|
1.68 (1.52, 1.86)
|
<0.0001
|
|
Insulin
|
9632
|
206.06
|
5.08 (4.60, 5.61)
|
3.73 (3.35, 4.14)
|
<0.0001
|
|
Metformin
|
172,813
|
30.87
|
0.76 (0.69, 0.82)
|
0.87 (0.79, 0.94)
|
0.0009
|
|
Pioglitazone
|
4678
|
24.15
|
0.59 (0.47, 0.73)
|
0.70 (0.56, 0.86)
|
0.0011
|
|
Rosiglitazone
|
504
|
35.64
|
0.78 (0.48, 1.23)
|
0.89 (0.55, 1.42)
|
0.6296
|
|
Ischemic stroke
|
|
Antidiabetic drug (ref. = DPP4i)
|
28,508
|
20.69
|
–
|
–
|
–
|
|
No antidiabetic drug
|
101,166
|
35.83
|
1.68 (1.49, 1.89)
|
1.42 (1.26, 1.60)
|
<0.0001
|
|
Sulfonylureas
|
110,618
|
21.95
|
1.03 (0.92, 1.16)
|
1.06 (0.94, 1.19)
|
0.3465
|
|
Acarbose
|
22,800
|
26.18
|
1.24 (1.08, 1.43)
|
1.09 (0.94, 1.25)
|
0.2432
|
|
Meglitinides
|
13,103
|
50.98
|
2.39 (2.07, 2.75)
|
1.58 (1.37, 1.81)
|
<0.0001
|
|
Insulin
|
9632
|
111.07
|
5.23 (4.58, 5.97)
|
3.99 (3.47, 4.56)
|
<0.0001
|
|
Metformin
|
172,813
|
20.61
|
0.97 (0.86, 1.08)
|
1.03 (0.92, 1.15)
|
0.5630
|
|
Pioglitazone
|
4678
|
13.25
|
0.62 (0.47, 0.82)
|
0.71 (0.53, 0.94)
|
0.0166
|
|
Rosiglitazone
|
504
|
23.76
|
0.99 (0.55, 1.75)
|
1.06 (0.59, 1.87)
|
0.8551
|
|
Myocardial infarction
|
|
Antidiabetic drug (ref. = DPP4i)
|
28,508
|
5.19
|
–
|
–
|
–
|
|
No antidiabetic drug
|
101,166
|
7.01
|
1.47 (1.20, 1.80)
|
1.45 (1.18, 1.78)
|
0.0003
|
|
Sulfonylureas
|
110,618
|
4.21
|
0.83 (0.68, 1.01)
|
0.98 (0.80, 1.78)
|
0.8257
|
|
Acarbose
|
22,800
|
5.08
|
1.00 (0.77, 1.29)
|
0.98 (0.75, 1.27)
|
0.8993
|
|
Meglitinides
|
13,103
|
9.53
|
1.89 (1.49, 2.39)
|
1.49 (1.17, 1.90)
|
0.0011
|
|
Insulin
|
9632
|
17.64
|
3.43 (2.72, 4.33)
|
2.77 (2.17, 3.51)
|
<0.0001
|
|
Metformin
|
172,813
|
3.30
|
0.66 (0.54, 0.79)
|
0.80 (0.50, 1.39)
|
0.0234
|
|
Pioglitazone
|
4678
|
3.63
|
0.70 (0.42, 1.16)
|
0.84 (0.50, 1.39)
|
0.5007
|
|
Rosiglitazone
|
504
|
3.96
|
0.81 (0.20, 3.23)
|
0.92 (0.23, 3.63)
|
0.9037
|
|
Heart failure
|
|
Antidiabetic drug (ref. = DPP4i)
|
28,508
|
15.92
|
–
|
–
|
–
|
|
No antidiabetic drug
|
101,166
|
25.23
|
1.50 (1.30, 1.71)
|
1.28 (1.11, 1.47)
|
0.0004
|
|
Sulfonylureas
|
110,618
|
11.78
|
0.71 (0.62, 0.81)
|
0.86 (0.74, 1.08)
|
0.0322
|
|
Acarbose
|
22,800
|
19.82
|
1.21 (1.03, 1.42)
|
1.08 (0.92, 1.26)
|
0.3227
|
|
Meglitinides
|
13,103
|
48.23
|
2.91 (2.48, 3.40)
|
1.85 (1.58, 2.16)
|
<0.0001
|
|
Insulin
|
9632
|
92.80
|
5.67 (4.87, 6.58)
|
3.71 (3.14, 4.37)
|
<0.0001
|
|
Metformin
|
172,813
|
8.51
|
0.51 (0.44, 0.59)
|
0.66 (0.57, 0.75)
|
<0.0001
|
|
Pioglitazone
|
4678
|
9.40
|
0.57 (0.39, 0.80)
|
0.76 (0.53, 1.07)
|
0.1229
|
|
Rosiglitazone
|
504
|
7.92
|
0.42 (0.15, 1.13)
|
0.53 (0.19, 1.46)
|
0.2226
|
|
Hypoglycemia
|
|
Antidiabetic drug (ref. = DPP4i)
|
28,508
|
5.82
|
–
|
–
|
–
|
|
No antidiabetic drug
|
101,166
|
5.23
|
0.83 (0.67, 1.00)
|
0.76 (0.62, 0.92)
|
0.0053
|
|
Sulfonylureas
|
110,618
|
6.21
|
1.00 (0.84, 1.19)
|
1.08 (0.91, 1.29)
|
0.3621
|
|
Acarbose
|
22,800
|
5.83
|
0.96 (0.77, 1.19)
|
0.90 (0.72, 1.11)
|
0.3402
|
|
Meglitinides
|
13,103
|
18.16
|
2.91 (2.35, 3.59)
|
2.09 (1.68, 2.58)
|
<0.0001
|
|
Insulin
|
9632
|
39.44
|
6.41 (5.24, 7.84)
|
4.55 (3.67, 5.64)
|
<0.0001
|
|
Metformin
|
172,813
|
2.69
|
0.43 (0.35, 0.52)
|
0.50 (0.41, 0.60)
|
<0.0001
|
|
Pioglitazone
|
4678
|
5.77
|
0.93 (0.62, 1.40)
|
1.07 (0.71, 1.60)
|
0.7471
|
|
Rosiglitazone
|
504
|
11.88
|
1.50 (0.66, 3.37)
|
1.58 (0.70, 3.55)
|
0.2679
|
- The results in italics above indicate significant findings in the Cox models
-
HR hazard ratio, CI confidence interval, MACEs major adverse cardiovascular events, DPP4i dipeptidyl peptidase-4 inhibitors
- * Adjusted hazard ratios were estimated from the Cox models adjusted for age, sex, diabetes duration, comorbidity history (hypertension, hyperlipidemia, coronary artery diseases, stroke, myocardial infarction, heart failure, Charlson comorbidity index), diabetic complications (via adapted diabetic complication severity index), co-medications (α-blockers, β-blockers, diuretics, calcium channel blockers, angiotensin-II-converting enzyme inhibitors/angiotensin receptor blockers, lipid-lowering agents, anti-platelet agents/anticoagulants, nitroglycerin, digoxin)
