Fig. 1Flow chart of the study design. MET, metformin; SU, sulfonylurea; DPP4i, dipeptidyl peptidase-4 inhibitor; TZD, thiazolidinedione.
Table 1Baseline characteristics by type of second-line antidiabetic medication
Variable |
MET+SU (n=4,447) |
MET+DPP4i (n=6,136) |
MET+TZD (n=617) |
P value |
Age, yr |
61.1±10.6 |
58.1±10.5 |
58.1±10.5 |
<0.001 |
Men, sex |
2,064 (46.4) |
2,927 (47.7) |
323 (52.4) |
0.018 |
Duration of MET monotherapy, mo |
10.1±3.5 |
10.3±3.6 |
10.2±3.6 |
0.002 |
Duration of second line therapy, mo |
20.3±17.2 |
19.7±15.7 |
18.6±16.5 |
<0.001 |
Comorbidities |
|
|
|
|
Hypertension |
3,166 (71.2) |
4,124 (67.2) |
410 (66.5) |
<0.001 |
Dyslipidemia |
3,155 (71.0) |
5,029 (82.0) |
482 (78.1) |
<0.001 |
Atrial fibrillation |
67 (1.5) |
108 (1.8) |
10 (1.6) |
0.599 |
Chronic kidney disease |
59 (1.3) |
65 (1.1) |
6 (1.0) |
0.405 |
Diabetic neuropathy |
652 (14.7) |
877 (14.3) |
69 (11.2) |
0.068 |
Diabetic nephropathy |
328 (7.4) |
662 (10.8) |
72 (11.7) |
<0.001 |
Charlson score, unit |
3.3±1.8 |
3.2±1.7 |
3.2±1.7 |
0.072 |
Intravitreal injection |
46 (1.0) |
60 (1.0) |
3 (0.5) |
0.429 |
Inclusion year |
|
|
|
<0.001 |
2009 |
2,120 (47.7) |
3,079 (50.2) |
355 (57.5) |
2010 |
1,113 (25.0) |
1,547 (25.2) |
128 (20.8) |
2011 |
685 (15.4) |
899 (14.7) |
84 (13.6) |
2012 |
529 (11.9) |
611 (10.0) |
50 (8.1) |
Table 2Hazard ratios for aggravation of diabetic retinopathy by type of second-line antidiabetic medication
Drugs |
PY |
No. of cases |
Event rate, /100,000 PY |
Adjusted 1a
|
Adjusted 2b
|
HR (95% CI) |
P value |
HR (95% CI) |
P value |
MET+SU |
7,087 |
3,271 |
46,154 |
1.00 |
|
1.00 |
|
MET+DPP4i |
7,835 |
4,217 |
53,823 |
0.74 (0.62–0.89) |
0.001 |
0.80 (0.66–0.97) |
0.024 |
MET+TZD |
948 |
399 |
42,089 |
0.45 (0.27–0.76) |
0.003 |
0.50 (0.29–0.84) |
0.009 |
Table 3Hazard ratios for aggravation of diabetic retinopathy by type of second-line antidiabetic medication in a subgroup with available health screening data
Drugs |
PY |
No. of cases |
Event rate, /100,000 PY |
Adjusted 1a
|
Adjusted 2b
|
HR (95% CI) |
P value |
HR (95% CI) |
P value |
MET+SU |
2,436 |
1,106 |
45,402 |
1.00 |
|
1.00 |
|
MET+DPP4i |
3,065 |
1,630 |
53,181 |
0.89 (0.64–1.24) |
0.493 |
0.92 (0.64–1.32) |
0.646 |
MET+TZD |
315 |
146 |
46,349 |
0.36 (0.11–1.13) |
0.079 |
0.38 (0.12–1.22) |
0.103 |