. | Any hypoglycemia . | Major hypoglycemia . | ||||||
---|---|---|---|---|---|---|---|---|
. | Saxagliptin (%) . | Placebo (%) . | HR (95% CI) . | P+ . | Saxagliptin (%) . | Placebo (%) . | HR (95% CI) . | P+ . |
Overall | 1,462/8,280 (17.7) | 1,277/8,212 (15.6) | 1.16 (1.08, 1.25) | 177/8,280 (2.1) | 140/8,212 (1.7) | 1.26 (1.01, 1.58) | ||
Age (years) | ||||||||
<65 | 671/3,990 (16.8) | 560/3,941 (14.2) | 1.20 (1.08, 1.35) | 0.408 | 60/3,990 (1.5) | 49/3,941 (1.2) | 1.22 (0.84, 1.78) | 0.368 |
≥65 to ≤75 | 629/3,336 (18.9) | 555/3,314 (16.7) | 1.16 (1.04, 1.30) | 78/3,336 (2.3) | 68/3,314 (2.1) | 1.15 (0.83, 1.59) | ||
>75 | 162/954 (17.0) | 162/957 (16.9) | 1.02 (0.82, 1.27) | 39/954 (4.1) | 23/957 (2.4) | 1.77 (1.07, 3.01) | ||
Sex | ||||||||
Male | 974/5,512 (17.7) | 862/5,525 (15.6) | 1.15 (1.05, 1.27) | 0.815 | 118/5,512 (2.1) | 88/5,525 (1.6) | 1.33 (1.01, 1.76) | 0.504 |
Female | 488/2,768 (17.6) | 415/2,687 (15.4) | 1.18 (1.03, 1.34) | 59/2,768 (2.1) | 52/2,687 (1.9) | 1.14 (0.79, 1.66) | ||
Race | ||||||||
White | 1,136/6,241 (18.2) | 977/6,166 (15.8) | 1.18 (1.08, 1.28) | 0.860 | 130/6,241 (2.1) | 104/6,166 (1.7) | 1.24 (0.96, 1.61) | 0.779 |
Black | 53/278 (19.1) | 56/290 (19.3) | 1.03 (0.71, 1.50) | 10/278 (3.6) | 10/290 (3.4) | 1.03 (0.42, 2.52) | ||
Asian | 153/896 (17.1) | 140/884 (15.8) | 1.10 (0.88, 1.39) | 18/896 (2.0) | 10/884 (1.1) | 1.83 (0.86, 4.12) | ||
Other* | 120/865 (13.9) | 104/872 (11.9) | 1.18 (0.91, 1.54) | 19/865 (2.2) | 16/872 (1.8) | 1.21 (0.62, 2.39) | ||
BMI (kg/m2) | ||||||||
≤30 | 664/3,829 (17.3) | 567/3,821 (14.8) | 1.20 (1.07, 1.34) | 0.509 | 83/3,829 (2.2) | 77/3,821 (2.0) | 1.09 (0.80, 1.49) | 0.195 |
>30 | 798/4,444 (18.0) | 705/4,369 (16.1) | 1.14 (1.03, 1.26) | 94/4,444 (2.1) | 63/4,369 (1.4) | 1.47 (1.07, 2.04) | ||
CVD or MRF | ||||||||
CVD | 1,174/6,494 (18.1) | 1,047/6,465 (16.2) | 1.14 (1.05, 1.24) | 0.287 | 137/6,494 (2.1) | 124/6,465 (1.9) | 1.11 (0.87, 1.42) | 0.011 |
MRF | 288/1,786 (16.1) | 230/1,747 (13.2) | 1.26 (1.06, 1.50) | 40/1,786 (2.2) | 16/1,747 (0.9) | 2.45 (1.40, 4.51) | ||
Renal failure# | ||||||||
Normal-mild | 1,156/6,986 (16.5) | 1,021/6,930 (14.7) | 1.14 (1.05, 1.24) | 0.667 | 105/6,986 (1.5) | 94/6,930 (1.4) | 1.11 (0.84, 1.47) | 0.033 |
Moderate | 266/1,122 (23.7) | 221/1,118 (19.8) | 1.25 (1.05, 1.49) | 64/1,122 (5.7) | 34/1,118 (3.0) | 1.91 (1.27, 2.92) | ||
Severe | 40/172 (23.3) | 35/164 (21.3) | 1.17 (0.74, 1.84) | 8/172 (4.7) | 12/164 (7.3) | 0.65 (0.26, 1.58) | ||
ACR | ||||||||
<30 | 813/4,867 (16.7) | 731/4,829 (15.1) | 1.12 (1.01, 1.24) | 0.476 | 76/4,867 (1.6) | 60/4,829 (1.2) | 1.26 (0.90, 1.77) | 0.988 |
≥30–300 | 426/2,217 (19.2) | 356/2,209 (16.1) | 1.24 (1.08, 1.43) | 64/2,217 (2.9) | 51/2,209 (2.3) | 1.26 (0.87, 1.83) | ||
>300 | 165/832 (19.8) | 151/806 (18.7) | 1.09 (0.88, 1.37) | 29/832 (3.5) | 24/806 (3.0) | 1.23 (0.71, 2.13) | ||
Diabetes duration (years) | ||||||||
<5 | 170/1,975 (8.6) | 139/1,941 (7.2) | 1.23 (0.98, 1.54) | 0.618 | 14/1,975 (0.7) | 8/1,941 (0.4) | 1.73 (0.74, 4.33) | 0.734 |
≥5–10 | 269/1,957 (13.7) | 228/1,968 (11.6) | 1.20 (1.00, 1.43) | 32/1,957 (1.6) | 25/1,968 (1.3) | 1.32 (0.78, 2.25) | ||
≥10–15 | 346/1,764 (19.6) | 277/1,736 (16.0) | 1.26 (1.07, 1.47) | 40/1,764 (2.3) | 26/1,736 (1.5) | 1.46 (0.89, 2.42) | ||
≥15–20 | 260/1,027 (25.3) | 257/1,084 (23.7) | 1.10 (0.92, 1.30) | 27/1,027 (2.6) | 30/1,084 (2.8) | 0.98 (0.58, 1.66) | ||
≥20 | 417/1,547 (27.0) | 375/1,478 (25.4) | 1.09 (0.94, 1.25) | 64/1,547 (4.1) | 51/1,478 (3.5) | 1.20 (0.83, 1.74) | ||
Baseline HbA1c (%) | ||||||||
<6.5 | 73/590 (12.4) | 66/673 (9.8) | 1.28 (0.92, 1.79) | 0.016 | 13/590 (2.2) | 6/673 (0.9) | 2.38 (0.94, 6.80) | 0.072 |
≥6.5–7 | 234/1,442 (16.2) | 157/1,414 (11.1) | 1.53 (1.25, 1.87) | 31/1,442 (2.1) | 17/1,414 (1.2) | 1.83 (1.02, 3.38) | ||
≥7–8 | 497/2,759 (18.0) | 450/2,657 (16.9) | 1.07 (0.94, 1.22) | 58/2,759 (2.1) | 51/2,657 (1.9) | 1.06 (0.73, 1.55) | ||
≥8–9 | 347/1,577 (22.0) | 304/1,562 (19.5) | 1.16 (1.00, 1.35) | 38/1,577 (2.4) | 24/1,562 (1.5) | 1.58 (0.95, 2.66) | ||
≥9 | 288/1,761 (16.4) | 288/1,764 (16.3) | 1.01 (0.86, 1.19) | 34/1,761 (1.9) | 42/1,764 (2.4) | 0.83 (0.52, 1.30) | ||
≤7 | 384/2,374 (16.2) | 268/2,393 (11.2) | 1.50 (1.29, 1.76) | <0.001 | 54/2,374 (2.3) | 28/2,393 (1.2) | 1.99 (1.27, 3.19) | 0.016 |
>7 | 1,055/5,755 (18.3) | 997/5,677 (17.6) | 1.06 (0.97, 1.15) | 120/5,755 (2.1) | 112/5,677 (2.0) | 1.05 (0.82, 1.37) | ||
No baseline antidiabetic medications | 21/370 (5.7) | 17/417 (4.1) | 1.43 (0.76, 2.75) | 3/370 (0.8) | 1/417 (0.2) | NA | ||
Metformin alone | 76/1,588 (4.8) | 81/1,554 (5.2) | 0.92 (0.67, 1.26) | 6/1,588 (0.4) | 5/1,554 (0.3) | 1.21 (0.36, 4.19) | ||
SUR + metformin | 466/2,576 (18.1) | 327/2,549 (12.8) | 1.47 (1.27, 1.69) | 47/2,576 (1.8) | 22/2,549 (0.9) | 2.13 (1.30, 3.61) | ||
Taking SUR | 575/3,327 (17.3) | 411/3,259 (12.6) | 1.42 (1.25, 1.61) | 61/3,327 (1.8) | 35/3,259 (1.1) | 1.73 (1.15, 2.64) | ||
HbA1c ≤7% | 185/849 (21.8) | 107/838 (12.8) | 1.80 (1.42, 2.30) | 0.013 | 28/849 (3.3) | 12/838 (1.4) | 2.36 (1.23, 4.82) | 0.179 |
HbA1c >7% | 377/2,415 (15.6) | 298/2,372 (12.6) | 1.27 (1.09, 1.48) | 31/2,415 (1.3) | 23/2,372 (1.0) | 1.33 (0.78, 2.31) | ||
Not taking SUR | 887/4,953 (17.9) | 866/4,951 (17.5) | 1.04 (0.95, 1.14) | 116/4,953 (2.3) | 105/4,951 (2.1) | 1.12 (0.86, 1.46) | ||
HbA1c ≤7% | 199/1,525 (13.0) | 161/1,555 (10.4) | 1.31 (1.06, 1.61) | 0.011 | 26/1,525 (1.7) | 16/1,555 (1.0) | 1.73 (0.94, 3.29) | 0.117 |
HbA1c >7% | 678/3,340 (20.3) | 699/3,305 (21.1) | 0.96 (0.87, 1.07) | 89/3,340 (2.7) | 89/3,305 (2.7) | 0.99 (0.74, 1.33) | ||
Taking insulin | 930/3,423 (27.2) | 904/3,364 (26.9) | 1.03 (0.94, 1.13) | 117/3,423 (3.4) | 108/3,364 (3.2) | 1.07 (0.83, 1.40) | ||
HbA1c ≤7% | 190/563 (33.7) | 133/519 (25.6) | 1.41 (1.13, 1.76) | 0.001 | 27/563 (4.8) | 14/519 (2.7) | 1.76 (0.94, 3.46) | 0.071 |
HbA1c >7% | 727/2,810 (25.9) | 764/2,800 (27.3) | 0.96 (0.86, 1.06) | 89/2,810 (3.2) | 94/2,800 (3.4) | 0.95 (0.71, 1.27) | ||
Type of SUR§ | ||||||||
Glibenclamide | 199/1,172 (17.0) | 132/1,160 (11.4) | 1.57 (1.26, 1.95) | 0.482 | 34/1,172 (2.9) | 15/1,160 (1.3) | 2.28 (1.26, 4.30) | 0.571 |
Glimepiride | 169/959 (17.6) | 112/932 (12.0) | 1.50 (1.18, 1.91) | 14/959 (1.5) | 10/932 (1.1) | 1.27 (0.56, 2.96) | ||
Glipizide | 82/441 (18.6) | 74/451 (16.4) | 1.17 (0.86, 1.61) | 9/441 (2.0) | 5/451 (1.1) | 1.91 (0.66, 6.21) | ||
Gliclazide | 113/678 (16.7) | 78/645 (12.1) | 1.42 (1.07, 1.90) | 4/678 (0.6) | 4/645 (0.6) | 0.88 (0.21, 3.76) |
. | Any hypoglycemia . | Major hypoglycemia . | ||||||
---|---|---|---|---|---|---|---|---|
. | Saxagliptin (%) . | Placebo (%) . | HR (95% CI) . | P+ . | Saxagliptin (%) . | Placebo (%) . | HR (95% CI) . | P+ . |
Overall | 1,462/8,280 (17.7) | 1,277/8,212 (15.6) | 1.16 (1.08, 1.25) | 177/8,280 (2.1) | 140/8,212 (1.7) | 1.26 (1.01, 1.58) | ||
Age (years) | ||||||||
<65 | 671/3,990 (16.8) | 560/3,941 (14.2) | 1.20 (1.08, 1.35) | 0.408 | 60/3,990 (1.5) | 49/3,941 (1.2) | 1.22 (0.84, 1.78) | 0.368 |
≥65 to ≤75 | 629/3,336 (18.9) | 555/3,314 (16.7) | 1.16 (1.04, 1.30) | 78/3,336 (2.3) | 68/3,314 (2.1) | 1.15 (0.83, 1.59) | ||
>75 | 162/954 (17.0) | 162/957 (16.9) | 1.02 (0.82, 1.27) | 39/954 (4.1) | 23/957 (2.4) | 1.77 (1.07, 3.01) | ||
Sex | ||||||||
Male | 974/5,512 (17.7) | 862/5,525 (15.6) | 1.15 (1.05, 1.27) | 0.815 | 118/5,512 (2.1) | 88/5,525 (1.6) | 1.33 (1.01, 1.76) | 0.504 |
Female | 488/2,768 (17.6) | 415/2,687 (15.4) | 1.18 (1.03, 1.34) | 59/2,768 (2.1) | 52/2,687 (1.9) | 1.14 (0.79, 1.66) | ||
Race | ||||||||
White | 1,136/6,241 (18.2) | 977/6,166 (15.8) | 1.18 (1.08, 1.28) | 0.860 | 130/6,241 (2.1) | 104/6,166 (1.7) | 1.24 (0.96, 1.61) | 0.779 |
Black | 53/278 (19.1) | 56/290 (19.3) | 1.03 (0.71, 1.50) | 10/278 (3.6) | 10/290 (3.4) | 1.03 (0.42, 2.52) | ||
Asian | 153/896 (17.1) | 140/884 (15.8) | 1.10 (0.88, 1.39) | 18/896 (2.0) | 10/884 (1.1) | 1.83 (0.86, 4.12) | ||
Other* | 120/865 (13.9) | 104/872 (11.9) | 1.18 (0.91, 1.54) | 19/865 (2.2) | 16/872 (1.8) | 1.21 (0.62, 2.39) | ||
BMI (kg/m2) | ||||||||
≤30 | 664/3,829 (17.3) | 567/3,821 (14.8) | 1.20 (1.07, 1.34) | 0.509 | 83/3,829 (2.2) | 77/3,821 (2.0) | 1.09 (0.80, 1.49) | 0.195 |
>30 | 798/4,444 (18.0) | 705/4,369 (16.1) | 1.14 (1.03, 1.26) | 94/4,444 (2.1) | 63/4,369 (1.4) | 1.47 (1.07, 2.04) | ||
CVD or MRF | ||||||||
CVD | 1,174/6,494 (18.1) | 1,047/6,465 (16.2) | 1.14 (1.05, 1.24) | 0.287 | 137/6,494 (2.1) | 124/6,465 (1.9) | 1.11 (0.87, 1.42) | 0.011 |
MRF | 288/1,786 (16.1) | 230/1,747 (13.2) | 1.26 (1.06, 1.50) | 40/1,786 (2.2) | 16/1,747 (0.9) | 2.45 (1.40, 4.51) | ||
Renal failure# | ||||||||
Normal-mild | 1,156/6,986 (16.5) | 1,021/6,930 (14.7) | 1.14 (1.05, 1.24) | 0.667 | 105/6,986 (1.5) | 94/6,930 (1.4) | 1.11 (0.84, 1.47) | 0.033 |
Moderate | 266/1,122 (23.7) | 221/1,118 (19.8) | 1.25 (1.05, 1.49) | 64/1,122 (5.7) | 34/1,118 (3.0) | 1.91 (1.27, 2.92) | ||
Severe | 40/172 (23.3) | 35/164 (21.3) | 1.17 (0.74, 1.84) | 8/172 (4.7) | 12/164 (7.3) | 0.65 (0.26, 1.58) | ||
ACR | ||||||||
<30 | 813/4,867 (16.7) | 731/4,829 (15.1) | 1.12 (1.01, 1.24) | 0.476 | 76/4,867 (1.6) | 60/4,829 (1.2) | 1.26 (0.90, 1.77) | 0.988 |
≥30–300 | 426/2,217 (19.2) | 356/2,209 (16.1) | 1.24 (1.08, 1.43) | 64/2,217 (2.9) | 51/2,209 (2.3) | 1.26 (0.87, 1.83) | ||
>300 | 165/832 (19.8) | 151/806 (18.7) | 1.09 (0.88, 1.37) | 29/832 (3.5) | 24/806 (3.0) | 1.23 (0.71, 2.13) | ||
Diabetes duration (years) | ||||||||
<5 | 170/1,975 (8.6) | 139/1,941 (7.2) | 1.23 (0.98, 1.54) | 0.618 | 14/1,975 (0.7) | 8/1,941 (0.4) | 1.73 (0.74, 4.33) | 0.734 |
≥5–10 | 269/1,957 (13.7) | 228/1,968 (11.6) | 1.20 (1.00, 1.43) | 32/1,957 (1.6) | 25/1,968 (1.3) | 1.32 (0.78, 2.25) | ||
≥10–15 | 346/1,764 (19.6) | 277/1,736 (16.0) | 1.26 (1.07, 1.47) | 40/1,764 (2.3) | 26/1,736 (1.5) | 1.46 (0.89, 2.42) | ||
≥15–20 | 260/1,027 (25.3) | 257/1,084 (23.7) | 1.10 (0.92, 1.30) | 27/1,027 (2.6) | 30/1,084 (2.8) | 0.98 (0.58, 1.66) | ||
≥20 | 417/1,547 (27.0) | 375/1,478 (25.4) | 1.09 (0.94, 1.25) | 64/1,547 (4.1) | 51/1,478 (3.5) | 1.20 (0.83, 1.74) | ||
Baseline HbA1c (%) | ||||||||
<6.5 | 73/590 (12.4) | 66/673 (9.8) | 1.28 (0.92, 1.79) | 0.016 | 13/590 (2.2) | 6/673 (0.9) | 2.38 (0.94, 6.80) | 0.072 |
≥6.5–7 | 234/1,442 (16.2) | 157/1,414 (11.1) | 1.53 (1.25, 1.87) | 31/1,442 (2.1) | 17/1,414 (1.2) | 1.83 (1.02, 3.38) | ||
≥7–8 | 497/2,759 (18.0) | 450/2,657 (16.9) | 1.07 (0.94, 1.22) | 58/2,759 (2.1) | 51/2,657 (1.9) | 1.06 (0.73, 1.55) | ||
≥8–9 | 347/1,577 (22.0) | 304/1,562 (19.5) | 1.16 (1.00, 1.35) | 38/1,577 (2.4) | 24/1,562 (1.5) | 1.58 (0.95, 2.66) | ||
≥9 | 288/1,761 (16.4) | 288/1,764 (16.3) | 1.01 (0.86, 1.19) | 34/1,761 (1.9) | 42/1,764 (2.4) | 0.83 (0.52, 1.30) | ||
≤7 | 384/2,374 (16.2) | 268/2,393 (11.2) | 1.50 (1.29, 1.76) | <0.001 | 54/2,374 (2.3) | 28/2,393 (1.2) | 1.99 (1.27, 3.19) | 0.016 |
>7 | 1,055/5,755 (18.3) | 997/5,677 (17.6) | 1.06 (0.97, 1.15) | 120/5,755 (2.1) | 112/5,677 (2.0) | 1.05 (0.82, 1.37) | ||
No baseline antidiabetic medications | 21/370 (5.7) | 17/417 (4.1) | 1.43 (0.76, 2.75) | 3/370 (0.8) | 1/417 (0.2) | NA | ||
Metformin alone | 76/1,588 (4.8) | 81/1,554 (5.2) | 0.92 (0.67, 1.26) | 6/1,588 (0.4) | 5/1,554 (0.3) | 1.21 (0.36, 4.19) | ||
SUR + metformin | 466/2,576 (18.1) | 327/2,549 (12.8) | 1.47 (1.27, 1.69) | 47/2,576 (1.8) | 22/2,549 (0.9) | 2.13 (1.30, 3.61) | ||
Taking SUR | 575/3,327 (17.3) | 411/3,259 (12.6) | 1.42 (1.25, 1.61) | 61/3,327 (1.8) | 35/3,259 (1.1) | 1.73 (1.15, 2.64) | ||
HbA1c ≤7% | 185/849 (21.8) | 107/838 (12.8) | 1.80 (1.42, 2.30) | 0.013 | 28/849 (3.3) | 12/838 (1.4) | 2.36 (1.23, 4.82) | 0.179 |
HbA1c >7% | 377/2,415 (15.6) | 298/2,372 (12.6) | 1.27 (1.09, 1.48) | 31/2,415 (1.3) | 23/2,372 (1.0) | 1.33 (0.78, 2.31) | ||
Not taking SUR | 887/4,953 (17.9) | 866/4,951 (17.5) | 1.04 (0.95, 1.14) | 116/4,953 (2.3) | 105/4,951 (2.1) | 1.12 (0.86, 1.46) | ||
HbA1c ≤7% | 199/1,525 (13.0) | 161/1,555 (10.4) | 1.31 (1.06, 1.61) | 0.011 | 26/1,525 (1.7) | 16/1,555 (1.0) | 1.73 (0.94, 3.29) | 0.117 |
HbA1c >7% | 678/3,340 (20.3) | 699/3,305 (21.1) | 0.96 (0.87, 1.07) | 89/3,340 (2.7) | 89/3,305 (2.7) | 0.99 (0.74, 1.33) | ||
Taking insulin | 930/3,423 (27.2) | 904/3,364 (26.9) | 1.03 (0.94, 1.13) | 117/3,423 (3.4) | 108/3,364 (3.2) | 1.07 (0.83, 1.40) | ||
HbA1c ≤7% | 190/563 (33.7) | 133/519 (25.6) | 1.41 (1.13, 1.76) | 0.001 | 27/563 (4.8) | 14/519 (2.7) | 1.76 (0.94, 3.46) | 0.071 |
HbA1c >7% | 727/2,810 (25.9) | 764/2,800 (27.3) | 0.96 (0.86, 1.06) | 89/2,810 (3.2) | 94/2,800 (3.4) | 0.95 (0.71, 1.27) | ||
Type of SUR§ | ||||||||
Glibenclamide | 199/1,172 (17.0) | 132/1,160 (11.4) | 1.57 (1.26, 1.95) | 0.482 | 34/1,172 (2.9) | 15/1,160 (1.3) | 2.28 (1.26, 4.30) | 0.571 |
Glimepiride | 169/959 (17.6) | 112/932 (12.0) | 1.50 (1.18, 1.91) | 14/959 (1.5) | 10/932 (1.1) | 1.27 (0.56, 2.96) | ||
Glipizide | 82/441 (18.6) | 74/451 (16.4) | 1.17 (0.86, 1.61) | 9/441 (2.0) | 5/451 (1.1) | 1.91 (0.66, 6.21) | ||
Gliclazide | 113/678 (16.7) | 78/645 (12.1) | 1.42 (1.07, 1.90) | 4/678 (0.6) | 4/645 (0.6) | 0.88 (0.21, 3.76) |
+P values represent interaction between subgroups and treatment allocation.
*Other: multiracial, Native Hawaiian, or other Pacific, American Indian, or Alaska native.
#Renal function categories defined as normal function–mild impairment (eGFR >50 mL/min), moderate impairment (eGFR = 30–50 mL/min), and severe impairment (eGFR <30 mL/min).
§Among patients taking SUR, excluding those taking more than one type of SUR, excluding tolbutamide and other SUR use.