Estimated HRs and 95% CIs of patients with incident dementia for T2D treated with SU, TZD, MET and SU, MET and TZD, and SU and TZD compared with MET monotherapy*
| All-cause dementia | AD | VaD | |||||||
| Treatment | Event | Unadjusted HR (95% CI) | Adjusted HR (95% CI)† | Event | Unadjusted HR (95% CI) | Adjusted HR (95% CI)† | Event | Unadjusted HR (95% CI) | Adjusted HR (95% CI)† |
| Primary analysis: 1-year exposure | |||||||||
| SU | 11 689 | 1.14 (1.11 to 1.16) | 1.12 (1.09 to 1.15) | 1200 | 0.99 (0.92 to 1.08) | 0.97 (0.90 to 1.05) | 922 | 1.14 (1.04 to 1.25) | 1.14 (1.04 to 1.24) |
| TZD | 450 | 0.81 (0.77 to 0.83) | 0.78 (0.75 to 0.81) | 62 | 0.93 (0.83 to 1.05) | 0.89 (0.79 to 0.99) | 19 | 0.44 (0.37 to 0.52) | 0.43 (0.37 to 0.51) |
| MET and SU | 6725 | 1.17 (1.14 to 1.2) | 1.14 (1.11 to 1.18) | 634 | 1.10 (1.01 to 1.21) | 1.04 (0.95 to 1.14) | 611 | 1.09 (0.99 to 1.20) | 1.14 (1.04 to 1.26) |
| MET and TZD | 247 | 0.95 (0.91 to 0.98) | 0.89 (0.86 to 0.93) | 22 | 0.89 (0.79 to 0.99) | 0.81 (0.72 to 0.92) | 11 | 0.51 (0.44 to 0.59) | 0.48 (0.41 to 0.56) |
| SU and TZD | 493 | 1.11 (1.07 to 1.15) | 1.04 (1.01 to 1.08) | 55 | 0.93 (0.83 to 1.04) | 0.85 (0.76 to 0.95) | 30 | 1.13 (1.00 to 1.27) | 1.11 (0.99 to 1.25) |
| Exploratory analysis: 2-year exposure | |||||||||
| SU | 7031 | 1.19 (1.15 to 1.22) | 1.14 (1.11 to 1.18) | 689 | 1.09 (0.98 to 1.21) | 1.03 (0.93 to 1.14) | 557 | 1.20 (1.07 to 1.35) | 1.18 (1.05 to 1.33) |
| TZD | 285 | 0.62 (0.60 to 0.65) | 0.65 (0.62 to 0.68) | 36 | 0.73 (0.64 to 0.83) | 0.77 (0.67 to 0.89) | 5 | 0.27 (0.21 to 0.34) | 0.28 (0.22 to 0.36) |
| MET and SU | 3944 | 0.88 (0.85 to 0.91) | 0.91 (0.88 to 0.95) | 369 | 0.81 (0.73 to 0.91) | 0.84 (0.75 to 0.93) | 346 | 0.90 (0.80 to 1.02) | 0.91 (0.81 to 1.04) |
| MET and TZD | 151 | 0.66 (0.63 to 0.69) | 0.69 (0.66 to 0.72) | 14 | 0.86 (0.75 to 0.98) | 0.89 (0.78 to 1.01) | 7 | 0.14 (0.10 to 0.19) | 0.14 (0.10 to 0.20) |
| SU and TZD | 317 | 0.88 (0.84 to 0.91) | 0.9 (0.87 to 0.94) | 32 | 0.55 (0.48 to 0.65) | 0.57 (0.49 to 0.66) | 19 | 1.06 (0.92 to 1.23) | 1.08 (0.94 to 1.25) |
Boldfaced values representing estimated HRs are statistically different from those with a p value of <0.05.
*In the 1-year MET monotherapy group, the numbers of incident all-cause dementia, AD, and VaD were 11 521, 1169, and 949, respectively, and in the 2-year MET monotherapy group, the numbers of events were 7352, 719, and 583.
†Models were adjusted on the calendar year of individual baseline, baseline age, statin use, HbA1c, systolic blood pressure, diastolic blood pressure, and congestive heart failure history collected at baseline, because these variables remained unbalanced after matching, at least on the comparison.
AD, Alzheimer’s disease; HbA1c, glycated hemoglobin; MET, metformin; SU, sulfonylurea; T2D, type 2 diabetes; TZD, thiazolidinedione; VaD, vascular dementia.