1. Events / Person-Years (Annual Rate) Hazard Ratio More Intensive
Figure 1
Events / Person-Years (Annual Rate)
Hazard Ratio
More Intensive
Less Intensive
Trials
More Intensive
Less Intensive
Better
Better
(95% CI)
Primary Kidney Outcome
ACCORD
383/21641 (1.8%)
484/21554 (2.2%)
0.79 ( )
ADVANCE
233/25728 (0.9%)
301/25675 (1.2%)
0.77 ( )
UKPDS
127/10852 (1.2%)
54/4515 (1.2%)
0.98 ( )
VADT
18/3818 (0.5%)
26/3878 (0.7%)
0.70 ( )
Overall
761/62039 (1.2%)
865/55622 (1.6%)
0.80 ( )
(I2=0.0%, p=0.583)
Primary Eye Outcome
ACCORD
131/6135 (2.1%)
167/6104 (2.7%)
0.79 ( )
ADVANCE
35/2992 (1.2%)
49/2901 (1.7%)
0.83 ( )
UKPDS
200/5300 (3.8%)
88/2251 (3.9%)
0.95 ( )
VADT
62/450 (13.8%)
63/453 (13.9%)
0.94 ( )
Overall
428/14877 (2.9%)
367/11709 (3.1%)
0.87 ( )
(I2=0.0%, p=0.688)
Primary Nerve Outcome
ACCORD
2055/14979 (13.7%)
2210/14923 (14.8%)
0.92 ( )
ADVANCE
1373/23752 (5.8%)
1299/23876 (5.4%)
1.07 ( )
UKPDS
453/12247 (3.7%)
208/5087 (4.1%)
0.93 ( )
Overall
3881/50978 (7.6%)
3717/43887 (8.5%)
0.98 ( )
(I2=78.1%, p=0.011)
0.25
0.5 1 2
p is for Cochran’s Q test
Hazard Ratio

2. A B Figure 2 Events (Annual Rate) Hazard Ratio More Intensive
Less Intensive
More Intensive
Less Intensive
Better
Better
(95% CI)
Primary Kidney Outcome
761 (1.2%)
865 (1.6%)
0.80 ( )
End Stage Kidney Disease
113 (0.2%)
143 (0.2%)
0.61 ( )
Renal Death
18 (0.0%)
22 (0.1%)
0.77 ( )
eGFR<30ml/min/1.73m2
175 (0.3%)
149 (0.3%)
1.16 ( )
Macroalbuminuria
509 (0.9%)
603 (1.2%)
0.74 ( )
Secondary Outcomes
0.90 ( )
Microalbuminuria
2121 (5.2%)
2210 (6.3%) B
Less Intensive
More Intensive
Better
Better
Secondary Outcomes
Macro to Norm
80 (3.5%)
603 (1.2%)
1.01 ( )
Macro to Micro/Norm
353 (22.0%)
332 (18.1%)
1.23 ( )
Micro to Norm
1430 (13.0%)
1176 (10.7%)
1.15 ( )
Norm to Norm
7004 (75.5%)
5784 (72.4%)
1.16 ( )
0.25
0.5 1 2
Hazard Ratio

3. Figure 3
Events (Annual Rate)
More Intensive
Less Intensive
Hazard Ratio
More Intensive
Less Intensive
Better
Better
(95% CI)
Primary Eye Outcome
428(2.9%)
367(3.1%)
0.87( )
Photocoagulation/
Vitrectomy
675(1.1%)
665(1.3%)
0.96( )
Proliferative Retinopathy
223(0.7%)
210(0.7%)
0.93( )
ETDRS Progression
≥3 steps
339(2.1%)
288(2.3%)
0.86( )
Secondary Outcomes
Macular Edema
187(0.5%)
205(0.6%)
0.83( )
Blindness .
397(0.7%)
380(0.7%)
1.03( )
Vision Deterioration
4663(9.3%)
4615(10.7%)
0.97( )
Cataract Extraction
763(2.1%)
828(2.8%)
0.90( )
0.25
0.5 1 2
Hazard Ratio

4. Supplementary Figure 1
Events (Annual Rate)
More Intensive
Less Intensive
Hazard Ratio
More Intensive
Less Intensive
Better
Better
(95% CI)
Primary Nerve Outcome
3881 (7.6%)
3717 (8.5%)
0.98 ( )
Loss of Vibratory Sensation
808 (2.7%)
789 (3.5%)
0.91 ( )
Loss of Ankle Reflexes
2804 (6.1%)
2722 (7.0%)
0.97 ( )
Loss of Light touch
994 (1.8%)
1029 (2.1%)
0.91 ( )
0.25
0.5 1 2
Hazard Ratio

5. Supplementary Figure 2A (Primary Kidney Outcome)
Events (Annual Rate)
More Intensive
Less Intensive
Hazard Ratio P
Subgroups
More Intensive
Less Intensive
Better
Better
(95% CI)
interaction
OVERALL
Male
Female
Age < mean (62.3y)
Age ≥ mean (62.3y)
Age < 70y
Age ≥ 70y
HbA1c < 7.5%
HbA1c %
HbA1c > 8.5%
Caucasian
Asian
Hispanic
Black
Duration of diabetes < 5y
Duration of diabetes ≥ 5y
No existing CVD
Existing CVD
eGFR 1st third (<73 ml/min)
eGFR 2nd third (73-90 ml/min)
eGFR 3rd third (>90 ml/min)
761(1.2%)
480(1.3%)
291(1.2%)
392(1.2%)
379(1.3%)
607(1.2%)
164(1.5%)
260(1.0%)
223(1.3%)
277(1.6%)
472(1.2%)
47(2.2%)
92(1.6%)
139(1.1%)
256(1.0%)
513(1.4%)
496(1.1%)
275(1.6%)
348(1.7%)
192(0.9%)
223(1.1%)
865(1.6%)
568(1.7%)
301(1.4%)
402(1.5%)
467(1.6%)
684(1.5%)
185(1.7%)
239(1.1%)
282(1.7%)
338(2.0%)
520(1.5%)
41(1.9%)
101(1.9%)
171(1.5%)
225(1.2%)
642(1.8%)
547(1.4%)
322(1.9%)
413(2.2%)
224(1.2%)
229(1.2%)
0.80( )
0.80( )
0.84( )
0.83( )
0.78( )
0.79( )
0.93( )
0.90( )
0.72( )
0.81( )
0.81( )
0.76( )
0.79( )
0.75( )
0.80( )
0.80( )
0.78( )
0.84( )
0.75( )
0.86( )
0.816
0.645
0.415
0.251
0.682
0.952
0.398
0.517
0.25
0.5 1 2
Hazard Ratio

6. Supplementary Figure 2B (Primary Eye Outcome)
Events (Annual Rate)
More Intensive
Less Intensive
Hazard Ratio P
Subgroups
More Intensive
Less Intensive
Better
Better
(95% CI)
interaction
OVERALL
Male
Female
Age < mean (62.3y)
Age ≥ mean (62.3y)
Age < 70y
Age ≥ 70y
HbA1c < 7.5%
HbA1c %
HbA1c > 8.5%
Caucasian
Asian
Hispanic
Black
Duration of diabetes < 5y
Duration of diabetes ≥ 5y
No existing CVD
Existing CVD
eGFR 1st third (<73 ml/min)
eGFR 2nd third (73-90 ml/min)
eGFR 3rd third (>90 ml/min)
428(2.9%)
281(3.0%)
147(2.6%)
280(3.0%)
148(2.7%)
399(3.0%)
29(2.0%)
140(2.1%)
101(2.4%)
181(4.9%)
283(2.8%)
28(6.1%)
54(3.9%)
55(2.2%)
223(2.8%)
204(3.0%)
336(2.8%)
91(3.1%)
113(2.7%)
142(2.7%)
172(3.2%)
367(3.1%)
268(3.6%)
99(2.3%)
232(3.4%)
135(2.8%)
328(3.2%)
39(2.7%)
85(1.8%)
110(3.0%)
167(5.2%)
210(2.8%)
23(5.1%)
57(4.8%)
62(2.9%)
135(2.7%)
230(3.4%)
274(3.1%)
93(3.3%)
91(2.8%)
119(2.9%)
155(3.6%)
0.87( )
0.76( )
1.08( )
0.83( )
0.90( )
0.86( )
0.78( )
0.95( )
0.72( )
0.87( )
0.89( )
1.02( )
0.92( )
0.76( )
0.64( )
0.85( )
0.78( )
1.02( )
0.96( )
0.80( )
0.83( )
0.035
0.639
0.719
0.687
0.391
0.563
0.178
0.461
0.25
0.5 1 2
Hazard Ratio

7. Supplementary Figure 2C (Primary Nerve Outcome)
Events (Annual Rate)
More Intensive
Less Intensive
Hazard Ratio P
Subgroups
More Intensive
Less Intensive
Better
Better
(95% CI)
interaction
OVERALL
Male
Female
Age < mean (62.3y)
Age ≥ mean (62.3y)
Age < 70y
Age ≥ 70y
HbA1c < 7.5%
HbA1c %
HbA1c > 8.5%
Caucasian
Asian
Hispanic
Black
Duration of diabetes < 5y
Duration of diabetes ≥ 5y
No existing CVD
Existing CVD
eGFR 1st third (<73 ml/min)
eGFR 2nd third (73-90 ml/min)
eGFR 3rd third (>90 ml/min)
3881(7.6%)
2489(8.4%)
1392(6.5%)
1853(6.8%)
2028(8.5%)
3078(7.3%)
803(9.4%)
1463(6.0%)
1265(9.3%)
1103(9.2%)
2797(8.5%)
111(9.6%)
399(9.7%)
458(3.9%)
1311(5.3%)
2553(9.7%)
2681(7.0%)
1200(9.4%)
1349(7.9%)
1257(7.2%)
1258(7.7%)
3717(8.5%)
2363(9.2%)
1354(7.4%)
1682(8.1%)
2035(8.8%)
2890(8.2%)
827(9.7%)
1309(6.6%)
1267(10.4%)
1116(10.0%)
2638(9.8%)
129(11.3%)
413(12.4%)
401(3.6%)
1089(6.3%)
2607(9.8%)
2538(8.1%)
1178(9.3%)
1253(8.3%)
1237(8.5%)
1214(8.7%)
0.98( )
0.99( )
0.95( )
1.00( )
0.96( )
0.98( )
0.97( )
0.99( )
0.95( )
0.98( )
0.97( )
0.86( )
0.89( )
0.87( )
0.94( )
1.01( )
0.96( )
1.00( )
1.00( )
0.93( )
0.99( )
0.656
0.694
0.901
0.847
0.870
0.449
0.714
0.978
0.25
0.5 1 2
Hazard Ratio