Characteristics of the study population
A total of 161,937 patients with new diagnosis T2DM at enrollment were selected from the NHIS database. Among them, 51,100 patients were identified on the basis of inclusion criteria aged ≥30 years with a prescription for antidiabetic medications. Further, 23,229 patients were excluded on the basis of the following exclusion criteria: less than 2 insurance claims each year (n = 491 patients), took antidiabetic drugs for less than180 days (n = 9,919 patients), and the presence of an end-stage disease (n = 2,083 patients) (Figure 1).
The final study population comprised 27,871 patients; their mean age was 57.28 years, 54.29% men and 45.71% women, and the mean duration of follow up was 6.56 ± 2.81 years. The major concomitant diseases were hypertension in 66.94% and dyslipidemia in 72.57% of patients. During the 2-year postdiagnosis period, 70.06% of the patients had taken metformin, 53.62% SU, 15.48% DPP4I, and 2.57% insulin. The adherence of antidiabetic drugs was 77.86% measured as medication possession rate. The concomitant medication was ACEI/ARB in 47.81% of the patients, DHP-CCB in 40.67%, and statin in 46.52%. Of 27,871 patients, 9,130 patients (32.76%) had no complication, 9,015 patients (32.35%) had one, and 9,726 (34.90%) patients had two or more complications at the index date of 2 years postdiagnosis. Older patients were found to have more complications than younger patients. The CCI score for coexisting diseases was 1.66 ± 1.00 in patients with no complication, 2.62 ± 1.35 in patients with one, and 4.12 ± 1.82 in patients with two or more complications (Table 1).
Total diabetes complications at 2 years postdiagnosis and during the follow-up period
The number of patients with complications at the index date the 2-year postdiagnosis period was total 18,741. Patients with no complication was 9,130 (32.76%) at index date and 3,714 (13.33%) during the follow-up period; patients with one complication was 9,015 (48.10%) and 5,888 (24.37%) during the same periods, respectively. Two or more complications were observed in 9,726 (34.89%) and 18,269 (65.54%) patients during the same periods, respectively. Complications at the index date were the highest for neuropathy in 8,896 (47.47%) followed by cardiovascular complications in 7,508 (40.06%) and retinopathy in 5,739 (30.62%). Patients with complications at the end of follow-up period were 24,157 of 27,871 (86.67%) with the highest for neuropathy in 15,385 (63.69%), followed by cardiovascular complications in 12,652 (52.37%) and retinopathy in 11,698 (48.42%) of 24,157 patients (Supplement figure 1, Supplement table 3).
Incidence and relative risk of new-onset diabetes complications during the follow-up period
New additional complications not present at baseline developed in 18,741 of 27,871 (67.14%) patients during the follow-up period with the highest for neuropathy 9,913 (54.05%), followed by cardiovascular complications 7,738 (42.19%) and retinopathy 7,595 (41.41%) out of 18741 patients (Table 2).
The risk of new complications during the follow-up period increased with age, female, and a higher CCI score. As DCSI at index date increased, the risk of new complications increased by 26% [relative risk (RR) 1.26, 95% CI 1.28–1.27]. As expected the use of more than three antidiabetics was associated with the risk of new complications by 13% increase (RR 1.13, 95% CI 1.10–1.17); the risk was relatively higher in patients treated with insulin (RR 1.07, 95% CI 1.03–1.11) and relatively lower in patients treated with statins (RR 0.71, 95% CI 0.69–0.73) as the concomitant medication. On comparing several monotherapies of antidiabetic drugs with reference metformin, the risk of new complications was higher in patients treated with sulfonylurea (RR 1.29, 95% CI 1.27–1.32) than with DPP4-I (RR 0.77, 95% CI 0.70–0.85). On comparing dual therapy [metformin + SU, MS] with [metformin + DPP4-I, MD], patients treated with MD had a 29% (RR 0.71, 95% CI 0.69–0.73) lower risk of new complications (Table 3).
All-cause hospitalization
A total of 14,297 (51.30%) of the 27,871 patients were admitted to the hospital with frequency of 3.27±5.0. The mean frequency of hospitalization during the follow-up period was 2.96±5.69 in patients without complications, 3.15±4.57 with one complication, and 3.59±4.78 with two or more complications. The average duration of hospitalization was 54.94 days in patients without complications, 76.40 days with one complication, and 106 days with two or more complications (Supplement table 4).
The adjusted RR of hospitalization was 1.06 (95% CI 1.01–1.11) when DCSI was 1, and it increased to 1.34 (95% CI 1.23–1.47) when DCSI was ≥5 compared with when DCSI was 0 as the reference (Table 4, Supplement table 5).
All-cause mortality
Among the 27,871 patients, 2,302 (8.26%) died because of all causes. Overall, 490 (5.37%) of the 9,130 patients without complications, 659 (7.31%) of the 9,015 patients with one complication, and 1,153 (11.85%) of the 9,726 patients with two or more complications died (Supplement table 4). The ROC curve showed that DCSI was a useful indicator of mortality (Supplement figure 2). As the number of diabetes complications increased, the survival rate of patients decreased significantly (Figure 2). The adjusted hazard ratio of mortality increased to 1.05 (95% CI 0.93–1.19) when DCSI was 1 and 1.87 (95% CI 1.60–2.19) when DCSI was ≥5 compared with when DCSI was 0 as the reference (Table 4, Supplement table 6).