Baseline characteristics of patients with and without hypoglycemia during the trial
| . | Severe hypoglycemia . | Confirmed hypoglycemia . | ||
|---|---|---|---|---|
| Yes (n = 267) . | No (n = 9,073) . | Yes (n = 4,169) . | No (n = 5,171) . | |
| Male | 166 (62.2) | 5,837 (64.3) | 2,631 (63.1) | 3,372 (65.2) |
| Age, years | 66.4 ± 7.7 | 64.2 ± 7.2 | 64.6 ± 7.2 | 64.0 ± 7.3 |
| Diabetes duration, years | 16.0 ± 8.3 | 12.7 ± 8.0 | 14.6 ± 8.4 | 11.4 ± 7.4 |
| Insulin use | 180 (67.4) | 3,989 (44.0) | 2,321 (55.7) | 1,848 (35.7) |
| Geographic region | ||||
| Europe | 83 (31.1) | 3,213 (35.4) | 1,300 (31.2) | 1,996 (38.6) |
| North America | 96 (36.0) | 2,751 (30.3) | 1,329 (31.9) | 1,518 (29.4) |
| Asia | 17 (6.4) | 694 (7.6) | 319 (7.7) | 392 (7.6) |
| Rest of the world | 71 (26.6) | 2,415 (26.6) | 1,221 (29.3) | 1,265 (24.5) |
| HbA1c, % | 8.8 ± 1.7 | 8.7 ± 1.5 | 8.7 ± 1.5 | 8.7 ± 1.6 |
| HbA1c, mmol/mol | 72.9 ± 18.9 | 71.5 ± 16.6 | 71.4 ± 16.3 | 71.6 ± 17.0 |
| BMI, kg/m2 | 32.3 ± 6.4 | 32.5 ± 6.3 | 32.0 ± 6.2 | 32.9 ± 6.3 |
| Body weight, kg | 90.4 ± 22.5 | 91.8 ± 20.9 | 89.7 ± 20.6 | 93.4 ± 21.2 |
| Systolic blood pressure, mmHg | 137.8 ± 20.7 | 135.8 ± 17.6 | 135.3 ± 18.2 | 136.4 ± 17.4 |
| Diastolic blood pressure, mmHg | 75.5 ± 10.1 | 77.1 ± 10.2 | 76.1 ± 10.3 | 77.9 ± 10.1 |
| Heart rate, bpm | 73.4 ± 12.0 | 72.6 ± 11.4 | 72.3 ± 11.5 | 72.9 ± 11.2 |
| CV medication | ||||
| Antihypertensive therapy | 255 (95.5) | 8,376 (92.3) | 3,914 (93.9) | 4,717 (91.2) |
| β-Blockers | 146 (54.7) | 5,035 (55.5) | 2,389 (57.3) | 2,792 (54.0) |
| Diuretics | 151 (56.6) | 3,755 (41.4) | 1,857 (44.5) | 2,049 (39.6) |
| Statins | 196 (73.4) | 6,545 (72.1) | 3,177 (76.2) | 3,564 (68.9) |
| Platelet aggregation inhibitors | 174 (65.2) | 6,152 (67.8) | 2,976 (71.4) | 3,350 (64.8) |
| Established CVD (age ≥50 years) | 229 (85.8) | 7,369 (81.2) | 3,456 (82.9) | 4,142 (80.1) |
| Prior myocardial infarction | 89 (33.3) | 2,775 (30.6) | 1,347 (32.3) | 1,517 (29.3) |
| Prior stroke or transient ischemic attack | 51 (19.1) | 1,456 (16.0) | 686 (16.5) | 821 (15.9) |
| Prior revascularization | 108 (40.4) | 3,530 (38.9) | 1,730 (41.5) | 1,908 (36.9) |
| >50% stenosis of coronary, carotid, or lower-extremity arteries | 60 (22.5) | 2,319 (25.6) | 1,115 (26.7) | 1,264 (24.4) |
| Documented symptomatic CHD* | 16 (6.0) | 802 (8.8) | 349 (8.4) | 469 (9.1) |
| Documented asymptomatic cardiac ischemia† | 60 (22.5) | 2,412 (26.6) | 1,093 (26.2) | 1,379 (26.7) |
| Heart failure NYHA II–III | 56 (21.0) | 1,249 (13.8) | 559 (13.4) | 746 (14.4) |
| Chronic kidney disease‡ | 119 (44.6) | 2,188 (24.1) | 1,245 (29.9) | 1,062 (20.5) |
| CVD risk factors (age ≥60 years) | 38 (14.2) | 1,704 (18.8) | 713 (17.1) | 1,029 (19.9) |
| Microalbuminuria or proteinuria | 26 (9.7) | 1,033 (11.4) | 459 (11.0) | 600 (11.6) |
| Hypertension and left ventricular hypertrophy | 8 (3.0) | 491 (5.4) | 193 (4.6) | 306 (5.9) |
| Left ventricular systolic or diastolic dysfunction | 6 (2.2) | 388 (4.3) | 160 (3.8) | 234 (4.5) |
| Ankle-brachial index <0.9 | 10 (3.7) | 216 (2.4) | 88 (2.1) | 138 (2.7) |
| Renal function, eGFR mL/min/1.73 m2 | ||||
| Normal (≥90) | 67 (25.1) | 3,208 (35.4) | 1,228 (29.5) | 2,047 (39.6) |
| Mild impairment (60–89) | 82 (30.7) | 3,825 (42.2) | 1,767 (42.4) | 2,140 (41.4) |
| Moderate impairment (30–59) | 96 (36.0) | 1,838 (20.3) | 1,036 (24.9) | 898 (17.4) |
| Severe impairment (<30) | 22 (8.2) | 202 (2.2) | 138 (3.3) | 86 (1.7) |
| Creatinine, μmol/L | 108.4 ± 63.2 | 86.8 ± 38.3 | 92.3 ± 42.4 | 83.5 ± 36.4 |
| Albumin/creatinine ratio, mg/g | 536.9 ± 1,482.8 | 180.1 ± 874.3 | 217.6 ± 730.8 | 168.2 ± 1,014.3 |
| Alanine aminotransferase, units/L | 23.8 ± 14.1 | 26.8 ± 16.2 | 25.8 ± 15.7 | 27.6 ± 16.4 |
| Bilirubin, μmol/L | 7.3 ± 4.2 | 7.8 ± 4.2 | 7.5 ± 3.9 | 8.1 ± 4.4 |
| Sodium, mmol/L | 140.1 ± 2.8 | 140.0 ± 2.7 | 140.1 ± 2.7 | 139.9 ± 2.7 |
| Potassium, mmol/L | 4.6 ± 0.5 | 4.5 ± 0.5 | 4.5 ± 0.5 | 4.5 ± 0.5 |
| . | Severe hypoglycemia . | Confirmed hypoglycemia . | ||
|---|---|---|---|---|
| Yes (n = 267) . | No (n = 9,073) . | Yes (n = 4,169) . | No (n = 5,171) . | |
| Male | 166 (62.2) | 5,837 (64.3) | 2,631 (63.1) | 3,372 (65.2) |
| Age, years | 66.4 ± 7.7 | 64.2 ± 7.2 | 64.6 ± 7.2 | 64.0 ± 7.3 |
| Diabetes duration, years | 16.0 ± 8.3 | 12.7 ± 8.0 | 14.6 ± 8.4 | 11.4 ± 7.4 |
| Insulin use | 180 (67.4) | 3,989 (44.0) | 2,321 (55.7) | 1,848 (35.7) |
| Geographic region | ||||
| Europe | 83 (31.1) | 3,213 (35.4) | 1,300 (31.2) | 1,996 (38.6) |
| North America | 96 (36.0) | 2,751 (30.3) | 1,329 (31.9) | 1,518 (29.4) |
| Asia | 17 (6.4) | 694 (7.6) | 319 (7.7) | 392 (7.6) |
| Rest of the world | 71 (26.6) | 2,415 (26.6) | 1,221 (29.3) | 1,265 (24.5) |
| HbA1c, % | 8.8 ± 1.7 | 8.7 ± 1.5 | 8.7 ± 1.5 | 8.7 ± 1.6 |
| HbA1c, mmol/mol | 72.9 ± 18.9 | 71.5 ± 16.6 | 71.4 ± 16.3 | 71.6 ± 17.0 |
| BMI, kg/m2 | 32.3 ± 6.4 | 32.5 ± 6.3 | 32.0 ± 6.2 | 32.9 ± 6.3 |
| Body weight, kg | 90.4 ± 22.5 | 91.8 ± 20.9 | 89.7 ± 20.6 | 93.4 ± 21.2 |
| Systolic blood pressure, mmHg | 137.8 ± 20.7 | 135.8 ± 17.6 | 135.3 ± 18.2 | 136.4 ± 17.4 |
| Diastolic blood pressure, mmHg | 75.5 ± 10.1 | 77.1 ± 10.2 | 76.1 ± 10.3 | 77.9 ± 10.1 |
| Heart rate, bpm | 73.4 ± 12.0 | 72.6 ± 11.4 | 72.3 ± 11.5 | 72.9 ± 11.2 |
| CV medication | ||||
| Antihypertensive therapy | 255 (95.5) | 8,376 (92.3) | 3,914 (93.9) | 4,717 (91.2) |
| β-Blockers | 146 (54.7) | 5,035 (55.5) | 2,389 (57.3) | 2,792 (54.0) |
| Diuretics | 151 (56.6) | 3,755 (41.4) | 1,857 (44.5) | 2,049 (39.6) |
| Statins | 196 (73.4) | 6,545 (72.1) | 3,177 (76.2) | 3,564 (68.9) |
| Platelet aggregation inhibitors | 174 (65.2) | 6,152 (67.8) | 2,976 (71.4) | 3,350 (64.8) |
| Established CVD (age ≥50 years) | 229 (85.8) | 7,369 (81.2) | 3,456 (82.9) | 4,142 (80.1) |
| Prior myocardial infarction | 89 (33.3) | 2,775 (30.6) | 1,347 (32.3) | 1,517 (29.3) |
| Prior stroke or transient ischemic attack | 51 (19.1) | 1,456 (16.0) | 686 (16.5) | 821 (15.9) |
| Prior revascularization | 108 (40.4) | 3,530 (38.9) | 1,730 (41.5) | 1,908 (36.9) |
| >50% stenosis of coronary, carotid, or lower-extremity arteries | 60 (22.5) | 2,319 (25.6) | 1,115 (26.7) | 1,264 (24.4) |
| Documented symptomatic CHD* | 16 (6.0) | 802 (8.8) | 349 (8.4) | 469 (9.1) |
| Documented asymptomatic cardiac ischemia† | 60 (22.5) | 2,412 (26.6) | 1,093 (26.2) | 1,379 (26.7) |
| Heart failure NYHA II–III | 56 (21.0) | 1,249 (13.8) | 559 (13.4) | 746 (14.4) |
| Chronic kidney disease‡ | 119 (44.6) | 2,188 (24.1) | 1,245 (29.9) | 1,062 (20.5) |
| CVD risk factors (age ≥60 years) | 38 (14.2) | 1,704 (18.8) | 713 (17.1) | 1,029 (19.9) |
| Microalbuminuria or proteinuria | 26 (9.7) | 1,033 (11.4) | 459 (11.0) | 600 (11.6) |
| Hypertension and left ventricular hypertrophy | 8 (3.0) | 491 (5.4) | 193 (4.6) | 306 (5.9) |
| Left ventricular systolic or diastolic dysfunction | 6 (2.2) | 388 (4.3) | 160 (3.8) | 234 (4.5) |
| Ankle-brachial index <0.9 | 10 (3.7) | 216 (2.4) | 88 (2.1) | 138 (2.7) |
| Renal function, eGFR mL/min/1.73 m2 | ||||
| Normal (≥90) | 67 (25.1) | 3,208 (35.4) | 1,228 (29.5) | 2,047 (39.6) |
| Mild impairment (60–89) | 82 (30.7) | 3,825 (42.2) | 1,767 (42.4) | 2,140 (41.4) |
| Moderate impairment (30–59) | 96 (36.0) | 1,838 (20.3) | 1,036 (24.9) | 898 (17.4) |
| Severe impairment (<30) | 22 (8.2) | 202 (2.2) | 138 (3.3) | 86 (1.7) |
| Creatinine, μmol/L | 108.4 ± 63.2 | 86.8 ± 38.3 | 92.3 ± 42.4 | 83.5 ± 36.4 |
| Albumin/creatinine ratio, mg/g | 536.9 ± 1,482.8 | 180.1 ± 874.3 | 217.6 ± 730.8 | 168.2 ± 1,014.3 |
| Alanine aminotransferase, units/L | 23.8 ± 14.1 | 26.8 ± 16.2 | 25.8 ± 15.7 | 27.6 ± 16.4 |
| Bilirubin, μmol/L | 7.3 ± 4.2 | 7.8 ± 4.2 | 7.5 ± 3.9 | 8.1 ± 4.4 |
| Sodium, mmol/L | 140.1 ± 2.8 | 140.0 ± 2.7 | 140.1 ± 2.7 | 139.9 ± 2.7 |
| Potassium, mmol/L | 4.6 ± 0.5 | 4.5 ± 0.5 | 4.5 ± 0.5 | 4.5 ± 0.5 |
Values are mean ± SD or number of patients (proportion of patients with or without severe or confirmed hypoglycemia [%]). CHD, coronary heart disease; CVD, cardiovascular disease; NYHA, New York Heart Association.
*Positive exercise stress test or any cardiac imaging or unstable angina with electrocardiogram changes.
†Positive nuclear imaging test, exercise test, or dobutamine stress echo.
‡eGFR <60 mL/min/1.73 m2 per MDRD formula or Cockcroft-Gault formula.