Table 3 Sensitivity and sub-cohort analyses for the event rate and hazard ratio (95% confidence interval) of study outcomes for intermediate-acting human insulin versus long-acting insulin analogue (reference group).
Event rate per 1000 person-years (no. of events) | Adjusted HRc (95% CI) | ||
|---|---|---|---|
IAHI | LAIA | ||
Sensitivity analysis 1: intention-to-treat analysis | (nb = 8479) | (nb = 8479) | |
Composite CVDs | 4.92 (158) | 2.94 (103) | 1.73 (1.35–2.23) |
Three-point MACEa | 3.19 (103) | 1.90 (67) | 1.73 (1.27–2.36) |
Microvascular diseases | 569.57 (6344) | 657.86 (6988) | 0.88 (0.85–0.91) |
Nephropathy | 182.47 (3947) | 188.15 (4305) | 0.93 (0.89–0.97) |
Retinopathy | 226.19 (4208) | 273.15 (5063) | 0.85 (0.81–0.88) |
Neuropathy | 116.58 (2737) | 116.64 (2978) | 0.97 (0.92–1.02) |
Hospitalized hypoglycemia | 27.29 (836) | 25.33 (849) | 1.06 (0.96–1.17) |
All-cause mortality | 2.62 (85) | 1.56 (55) | 1.68 (1.19–2.38) |
Fatal CVD | 1.29 (42) | 0.76 (27) | 1.78 (1.09–2.90) |
Sensitivity analysis 2: 3 years of maximum observational time | (nb = 8479) | (nb = 8479) | |
Composite CVDs | 7.53 (46) | 3.46 (36) | 2.12 (1.35–3.32) |
Three-point MACEa | 3.92 (24) | 1.34 (14) | 2.68 (1.37–5.26) |
Microvascular diseases | 1188.53 (3978) | 1116.59 (5049) | 0.88 (0.84–0.91) |
Nephropathy | 423.51 (2021) | 339.86 (2560) | 0.89 (0.84–0.94) |
Retinopathy | 419.23 (1967) | 434.59 (3000) | 0.85 (0.80–0.90) |
Neuropathy | 252.57 (1322) | 194.30 (1667) | 0.94 (0.87–1.01) |
Hospitalized hypoglycemia | 38.09 (229) | 19.87 (204) | 1.81 (1.49–2.20) |
All-cause mortality | 2.45 (15) | 0.48 (5) | 5.02 (1.79–14.08) |
Fatal CVD | 1.31 (8) | 0.19 (2) | 6.18 (1.28–29.93) |
Sensitivity analysis 3: lag-time analysis | (nb = 8479) | (nb = 8479) | |
Composite CVDs | 7.43 (48) | 4.56 (56) | 1.77 (1.18–2.64) |
Three-point MACEa | 3.71 (24) | 2.52 (31) | 1.70 (0.97–2.96) |
Microvascular diseases | 1001.51 (3742) | 944.64 (4917) | 0.90 (0.86–0.94) |
Nephropathy | 384.40 (1969) | 293.92 (2573) | 0.92 (0.87–0.98) |
Retinopathy | 354.65 (1783) | 371.27 (2904) | 0.84 (0.79–0.89) |
Neuropathy | 220.58 (1232) | 164.60 (1655) | 0.94 (0.87–1.01) |
Hospitalized hypoglycemia | 34.33 (218) | 18.76 (227) | 1.79 (1.48–2.17) |
All-cause mortality | 2.32 (15) | 1.87 (23) | 1.73 (0.87–3.42) |
Fatal CVD | 1.24 (8) | 1.62 (20) | 1.16 (0.49–2.75) |
Sensitivity analysis 4: excluding matched sets with a difference in propensity score of > 0.1 | (nb = 7451) | (nb = 7451) | |
Composite CVDs | 7.59 (45) | 4.91 (53) | 1.77 (1.17–2.67) |
Three-point MACEa | 3.70 (22) | 2.78 (30) | 1.64 (0.93–2.91) |
Microvascular diseases | 1104.57 (3483) | 1061.14 (4510) | 0.86 (0.82–0.90) |
Nephropathy | 386.91 (1777) | 304.02 (2322) | 0.90 (0.85–0.96) |
Retinopathy | 394.09 (1753) | 409.54 (2724) | 0.83 (0.78–0.88) |
Neuropathy | 1104.57 (3483) | 1061.14 (4510) | 0.86 (0.82–0.90) |
Hospitalized hypoglycemia | 35.58 (207) | 18.81 (200) | 1.83 (1.49–2.23) |
All-cause mortality | 2.02 (12) | 2.03 (22) | 1.53 (0.74–3.18) |
Fatal CVD | 1.18 (7) | 1.85 (20) | 1.53 (0.74–3.18) |
Sub-cohort analysis: excluding the patients with cardiovascular or microvascular disease history | (nb = 3779) | (nb = 3779) | |
Composite CVDs | 2.84 (9) | 0.56 (3) | 3.99 (1.02–15.56) |
Three-point MACEa | 1.57 (5) | 0.00 (0) | N/A |
Microvascular diseases | 493.36 (1074) | 452.65 (1488) | 0.90 (0.83–0.97) |
Nephropathy | 132.61 (375) | 100.49 (487) | 1.10 (0.96–1.26) |
Retinopathy | 257.70 (653) | 247.19 (959) | 0.86 (0.78–0.95) |
Neuropathy | 100.44 (292) | 91.06 (441) | 0.88 (0.76–1.03) |
Hospitalized hypoglycemia | 28.57 (89) | 10.04 (53) | 2.49 (1.76–3.53) |
All-cause mortality | 0.00 (0) | 0.19 (1) | N/A |
Fatal CVD | 0.00 (0) | 0.00 (0) | N/A |
