Overall, 3,882 patients newly entering chronic haemodialysis in 2016–2020 were enrolled in our study (Fig. 1; Table 1, Additional File 3). Two-thirds of the cohort are men; over 63% were 65 years or older at first dialysis.

Attrition diagram of the cohort selection

In general, the dialytic population is affected by numerous comorbidities. Patients suffering from type-2 diabetes account for 16.1%. Among the other conditions, hypertension is the most frequent one, in over 35.8% of the population, followed by anaemia (23.0%), ischemic heart disease (12.9%) and heart failure (10.9%).

Use of the study drugs/drug groups generally increases across the four semesters, especially in the pre-dialysis period and the first semester after dialysis initiation, with mean values (STD) of 5.54 (3.35) in semester 1, 6.24 (3.37) in semester 2, 7.30 (2.84) in semester 3, and 6.25 (3.19) in semester 4.

Fig 2 shows the proportions of patients treated with drugs typically prescribed to the dialytic population in the four semesters around the start of dialysis. Drug therapy is frequent in our cohort and reflects the reported comorbidities. Cardiovascular therapy is the most prescribed group, along with antithrombotics and proton pump inhibitors (PPIs), followed by drugs for anaemia.

Proportions of haemodialysis patients using study drugs in the four semesters around dialysis start

For some drug classes, differences between semesters are observed. In particular, anti-anaemic therapy with iron and erythropoietin increases steeply in the six months before and after starting dialysis (iron: from 10.6 to 44.4%, erythropoietin: from 32.6 to 65.6%). Similar trends are observed for treatments for hyperkalaemia and hyperphosphatemia (from 9.0 to 35.0%) and anti-parathyroid agents (paricalcitol from 3.4 to 19.1% and cinacalcet/etelcalcetide from 0.5 to 7.2%).

Cardiovascular therapy maintains high levels in all semesters. The choice of the different drug classes changes after dialysis, with a sharp decrease in ACEIs/ARBS (from 51.1 to 25.6%) and a temporal increase in diuretics and Calcium-channel blockers, which peaks in the first semester after initiating dialysis and then drops below initial levels in the last semester (diuretics: 45.1%, 54.1%, 59.6%, 42.1%, Calcium-channel blockers: 47.55, 53.5%, 54.1%, 37.0%). The proportion of patients prescribed antithrombotics increases, peaking in semester 3 (43.0%, 46.2%, 55.1%, 49.3%).

The use of antidiabetic drugs is basically stable over time, but changes in the patterns of specific drug utilization are observed. Prescription of oral antidiabetics and combined therapy decreased (from 9.8 to 4.5% and from 3.5 to 1.4%, respectively) while the proportion of patients using insulin alone remained relatively stable over time, with an increase immediately after starting dialysis (13.5%, 13.7%, 16.0%, 13.9%).

Among the remaining drugs, an increase in use of PPIs (from 47.7 to 66.1%) and anti-infectives (from 21.3 to 27.9%), and a decrease in reducing plasma acid uric medicines is observed (from 34.3 to 19.1%), while proportions of use of all other agents remain stable.

Differences before and after entering dialysis were statistically significant for almost all drugs/drug classes, except for Insulin, Vitamin D, and Iron chelating agents/Drugs for the treatment of hyperkalaemia and hyperphosphatemia.

Results of the stratified analyses for antidiabetic drugs are shown in Fig. 3, and for all other drugs in the additional files (Additional files 4 and 5). Proportions of patients treated with oral antidiabetics alone are generally higher in men than in women. For insulin alone, a slight increase is observed in men (from 13.6% in semester 2 to 14.4% in semester 4), whereas in women, this is evident only immediately after the index date. The proportions of older patients treated with antidiabetics are higher than in the younger group. The decrease for oral formulations is steeper in older respect to younger patients (from 12.4 to 5.8% vs. from 5.5 to 2.4%). In contrast, for insulins, the proportion of younger users remains higher in the last semester than before (12.3% previous semester vs. 10.9% first semester), which is not the case in the older (14.9% vs. 15.0%).

Proportions of patients using antidiabetics in the semesters around dialysis start by sex and age

Results of the analysis of treatment intensity among users of selected cardiovascular and antidiabetic medications over the four semesters in terms of DDDs (mean and median values, as well as IQRs) are shown in Fig. 4 and in the additional file 6 for other cardiovascular drugs.

Intensity of therapy with diuretics, ACEIs/ARBs, and antidiabetics in the four semesters

The essential treatment adaptations were detected for diuretics: mean doses of diuretics increased sharply in the semester before and the two semesters after dialysis initiation in patients treated, and over time more than doubled (mean DDDs from 329.3 to 699.7), associated with increased variability (IQR semester 2 vs. IQR semester 4: from 113 to 338 to 150–1000).

For ACEIs/ARBs, reductions in mean DDDs were detected in the semester immediately before starting dialysis (from 336.2 to 305.3 mean DDDs), and levels remained stable after that.

Regarding antidiabetic therapy, doses are steadily reduced over time for insulins (from 235.2 to 213.4 mean DDDs), whereas variable trends are found for oral antidiabetics (179.2–174.6–158.2–166.6 mean DDDs) and combined therapy (332.2–291.4–302.5–321.0 mean DDDs).

These differences were all statistically significant.

Stratifying by sex (Fig. 5), no differences are found for insulins, with similar mean DDDs decreasing over the semesters for both sexes. Mean doses of oral formulations are higher in women in the first semester, but due to a steady reduction in women along with stable doses in men, in the last semester, mean DDDs are higher in men. For the combined therapy, doses increase in men and decrease in women.

Intensity of antidiabetic therapy in the four semesters by sex and age

Age-specific analyses (Fig. 5) show higher mean DDDs for the younger age group for all antidiabetic formulations. Insulin doses remain stable in 18–64-year-old patients. At the same time, they decrease in the 65 + age group, doses of oral drugs are reduced in all ages, and the combined therapy shows an initial decrease followed by an increase 1 year after dialysis initiation.

In general, for cardiovascular therapy, dose adaptations around the initiation of dialysis are observed for all agents (Additional File 6). For almost all cardiovascular agents, mean doses are higher in men, except for diuretics and beta blockers (Additional File 7). Younger patients are prescribed higher doses except for lipid modifiers and antithrombotics, with similar doses between age groups (Additional File 8).