HRs of all-cause mortality for each drug by duration of drug exposure
| (A) Full cohort n=360 437 | (B) Full cohort+IPSW n=360 437 | (C) DM Rx incident cohort n=143 693 | (D) Non-DM Rx incident cohort n=44 375 | ||
| HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | ||
| Metformin | ≤6 Months | 1.06 (1.02 to 1.10)* | 0.90 (0.87 to 0.94)† | 1.03 (0.95 to 1.11) | 1.29 (1.15 to 1.45) |
| >6 Months | 1.04 (1.01 to 1.07)* | 0.93 (0.91 to 0.96)† | 0.80 (0.75 to 0.86)† | 0.94 (0.85 to 1.04) | |
| Insulin | ≤6 Months | 1.75 (1.68 to 1.81)† | 1.50 (1.45 to 1.56)† | 1.83 (1.69 to 1.97)† | 1.89 (1.69 to 2.11) |
| >6 Months | 1.38 (1.34 to 1.42)† | 1.29 (1.26 to 1.33)† | 1.00 (0.90 to 1.11) | 1.08 (0.97 to 1.22) | |
| Sulfonylurea | ≤6 Months | 1.21 (1.16 to 1.27)† | 1.08 (1.03 to 1.12)* | 1.34 (1.21 to 1.47)† | 1.47 (1.28 to 1.68) |
| >6 Months | 1.12 (1.08 to 1.15)† | 1.04 (1.01 to 1.08)* | 1.00 (0.92 to 1.10) | 1.11 (0.99 to 1.25) | |
| Thiazolidinedione | ≤6 Months | 0.97 (0.91 to 1.03) | 0.90 (0.84 to 0.95)† | 0.90 (0.69 to 1.17) | 0.91 (0.68 to 1.20) |
| >6 Months | 1.10 (1.05 to 1.15)† | 1.03 (0.98 to 1.07) | 1.14 (0.91 to 1.41) | 1.24 (1.02 to 1.51) | |
| GLP-1 analogues | ≤6 Months | 0.82 (0.75 to 0.90)† | 0.85 (0.78 to 0.93)* | 0.80 (0.56 to 1.15) | 0.75 (0.46 to 1.22) |
| >6 Months | 0.68 (0.62 to 0.75)† | 0.72 (0.66 to 0.79) † | 0.54 (0.35 to 0.84)* | 0.58 (0.36 to 0.92) | |
| DPP-4 inhibitor | ≤6 Months | 1.00 (0.94 to 1.05) | 1.02 (0.97 to 1.07) | 0.93 (0.81 to 1.08) | 0.82 (0.68 to 1.00) |
| >6 Months | 0.89 (0.85 to 0.93)† | 0.93 (0.89 to 0.97)* | 0.81 (0.70 to 0.93)* | 0.79 (0.65 to 0.95) | |
| SGLT-2 inhibitor | ≤6 Months | 0.73 (0.62 to 0.87)† | 0.79 (0.66 to 0.93)* | 0.67 (0.41 to 1.08) | 0.37 (0.16 to 0.82) |
| >6 Months | 0.74 (0.60 to 0.90)* | 0.80 (0.66 to 0.98)* | 0.25 (0.09 to 0.66)* | 0.29 (0.09 to 0.90) | |
| Other glucose-lowering drugs | ≤6 Months | 0.98 (0.88 to 1.08) | 0.95 (0.86 to 1.05) | 1.18 (0.87 to 1.59) | 1.32 (0.90 to 1.95) |
| >6 Months | 0.96 (0.87 to 1.06) | 0.96 (0.87 to 1.06) | 0.84 (0.55 to 1.28) | 0.83 (0.55 to 1.27) | |
| Diuretics—thiazide/thiazide-like | ≤6 Months | 0.92 (0.89 to 0.96)† | 0.85 (0.82 to 0.89)† | 0.94 (0.87 to 1.01) | 0.90 (0.78 to 1.03) |
| >6 Months | 0.86 (0.84 to 0.89)† | 0.81 (0.79 to 0.84)† | 0.83 (0.79 to 0.87) | 0.72 (0.62 to 0.83)† | |
| Beta-blockers | ≤6 Months | 1.16 (1.12 to 1.21)† | 0.88 (0.85 to 0.92)† | 1.21 (1.13 to 1.30) | 1.11 (1.00 to 1.24) |
| >6 Months | 0.99 (0.96 to 1.02) | 0.86 (0.84 to 0.89)† | 0.80 (0.76 to 0.84) | 0.78 (0.70 to 0.87)† | |
| DHP CCB | ≤6 Months | 1.03 (0.99 to 1.07) | 0.95 (0.91 to 0.98)* | 1.08 (1.01 to 1.16) | 0.95 (0.83 to 1.09) |
| >6 Months | 0.95 (0.92 to 0.98)† | 0.94 (0.92 to 0.97)† | 0.84 (0.79 to 0.88) | 0.76 (0.66 to 0.88)† | |
| Non-DHP CCB | ≤6 Months | 1.12 (1.06 to 1.19)† | 1.29 (1.24 to 1.34)† | 1.06 (0.96 to 1.17) | 1.02 (0.85 to 1.24) |
| >6 Months | 0.99 (0.95 to 1.03) | 1.31 (1.27 to 1.35)† | 0.87 (0.81 to 0.94) | 0.87 (0.75 to 1.01) | |
| ACE inhibitors | ≤6 Months | 1.03 (0.99 to 1.07) | 0.86 (0.83 to 0.89)† | 1.08 (1.01 to 1.15) | 1.01 (0.91 to 1.13) |
| >6 Months | 0.93 (0.91 to 0.96)† | 0.82 (0.79 to 0.84)† | 0.81 (0.77 to 0.85) | 0.70 (0.63 to 0.78)† | |
| ARB | ≤6 Months | 0.90 (0.86 to 0.95)† | 0.80 (0.77 to 0.84)† | 0.95 (0.87 to 1.04) | 0.79 (0.66 to 0.94)* |
| >6 Months | 0.82 (0.80 to 0.85)† | 0.75 (0.73 to 0.77)† | 0.67 (0.64 to 0.72) | 0.63 (0.54 to 0.75)† | |
| Statin | ≤6 Months | 0.89 (0.85 to 0.92)† | 0.66 (0.64 to 0.69)† | 0.85 (0.79 to 0.91) | 0.72 (0.64 to 0.81)† |
| >6 Months | 0.77 (0.75 to 0.80)† | 0.65 (0.63 to 0.66)† | 0.58 (0.55 to 0.61) | 0.51 (0.46 to 0.56)† | |
Non-DM Rx=blood pressure medications/statin.
*0.001≤p value<0.05.
†P<0.001.
ARB, angiotensin receptor blocker; CCB, calcium-channel blocker; DHP, dihydropyridine; DM, diabetes medications; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; IPSW, inverse propensity score weight; SGLT-2, sodium-glucose cotransporter-2.