Our results show that the presence of severe diabetic complications increases the cumulative cost of outpatient prescription medication considerably in patients with type 1 diabetes. Notably, the presence of ESRD greatly increases the cost compared with the presence of MVD without ESRD. Our data also clearly show that the 11-year cumulative cost of diabetes medication remained rather stable irrespective of complication status and duration of diabetes. The cost of medication related to comorbidity was low in patients without severe complications regardless of the duration of diabetes. However, in all duration groups the costs increased substantially when ESRD was present. Since no considerable differences were observed in the cost of diabetes medications between complication groups or duration of diabetes groups, the increase was entirely due to the cost of medications related to comorbidity, especially ESRD.
It is well established that the treatment of ESRD considerably increases the total cost of diabetes [6, 21]. In the US in 2006, the mean annual cost of peritoneal dialysis was $53,000 per patient and haemodialysis was $72,000 per patient . In a German study  the mean total dialysis-related costs were €55,000 per patient in 2006, with 55% accounting for dialysis procedures and 22% dialysis-related medications. Our study also showed that medications associated with renal failure incur the highest costs of outpatient prescription medications in type 1 diabetes. It has been estimated that the prevalence of ESRD among patients with type 1 diabetes is approximately 1–2.5% . Similarly in Finland, patients with ESRD represent only 1.5% of all patients with type 1 diabetes (Finnish Kidney Register). However, extrapolation of our results to all patients with type 1 diabetes showed that they incur more than 10% of all outpatient prescription medication costs. Although the incidence of ESRD has decreased [24, 25], the number of ESRD patients is still increasing in Finland as well as worldwide due to the increasing incidence of diabetes, especially type 2 diabetes . From this point of view, our findings together with previous studies highlight the importance of prevention, early diagnosis and intensive treatment of chronic kidney disease. Therefore, all efforts that could prevent or slow down the progression of diabetic nephropathy to ESRD may also reduce the total cost of outpatient medications for type 1 diabetes.
When ESRD was present the cost of diabetes medication was substantially lower in all 10-year duration groups compared with patients without complications. There are some possible reasons for this observation. First of all, diabetes patients with decreasing GFR require reduced quantities of insulin . When GFR drops to between 10 and 50 ml/min, representing pre-dialysis status, a 25% reduction in the total insulin dose is recommended and, once the GFR drops below 10 ml/min (as is the case in ESRD), the recommended reduction is 50% . In addition, changes in dietary intake and exercise may decrease insulin requirements. Finally, the data from the DPR included only prescribed medications used in outpatient care. Thus, diabetes medications used in hospital were not included. The same trend was seen among patients with MVD only. At the baseline visit they had approximately 20% lower eGFR and 15% lower insulin dose/day than those without complications. Although patients were not diagnosed with ESRD, undoubtedly a subset of them had reduced kidney function.
There are a number of studies on medication costs in diabetes. However, longitudinal studies on medication costs in type 1 diabetes are rare, especially in Finland, the country with the world’s highest incidence of type 1 diabetes. To our knowledge this is one of the first studies that has estimated longitudinal medication costs by linking detailed clinical data from a nationally representative cohort of patients with type 1 diabetes to the drug register data. Mostly, medication studies have been based only on national registers without precise knowledge of the type of diabetes and with cross-sectional study design. Thus, a comparison of our findings with previous studies is difficult. It has to be emphasised that the study population in the present study is undoubtedly well characterised regarding the type of diabetes, clinical characteristics, medical history and the presence of diabetic complications. In consequence, we were able to take into account patients’ BMI and insulin dose when analysing the cost of diabetes medication, which made our results more detailed and reliable. Moreover, our study population was fairly representative, including 10% of all adult patients with type 1 diabetes in Finland. Also the geographical distribution of the patients was similar to the general distribution of people in Finland.
Previous studies [8, 10] have compared prescription medication costs in outpatients with type 1 diabetes and non-diabetic controls. According to these studies annual medication costs were 8 to 12 times higher in the patients with diabetes than in the non-diabetic individuals. Our study, instead, compared the prescription medication costs among patients with type 1 diabetes according to the presence of complications and duration of diabetes. We found that there is a large variation among patients with type 1 diabetes.
The present study, however, has some limitations that need to be considered. First, the main focus of this longitudinal study was to analyse the costs of outpatient prescription medications in patients with type 1 diabetes. Medications dispensed during hospital stays and over-the-counter medications, which are not prescribed by the physician, are not recorded in the DPR. The cost of bed-days in hospital includes medications costs. Therefore, the accurate patient-level data of inpatient costs of medication would have been difficult to calculate, especially during the long follow-up time. Nevertheless, the proportion of outpatient prescription medications represents approximately three-quarters of total medication sales, whereas the proportion of the medications used in hospitals accounts for only 16% . Obviously, the more complications patients have, the more hospitalisation periods they may have. According to a previous Finnish study  the total number of patients with type 1 diabetes hospitalised due to complications almost doubled when duration of diabetes increased from 9.5 to 16.5 years. Therefore, it is probable that among patients with type 1 diabetes and severe complications the outpatient costs underestimate the true medication cost. Moreover, with regard to dialysis methods, peritoneal dialytics are dispensed through pharmacies, but haemodialysis fluids are mainly administered by hospitals. Thus, haemodialysis fluids are not registered in the DPR. Patients staying permanently in institutional care are not entitled to drug reimbursement, and the drugs dispensed for them are not registered in the DPR either.
Second, although the coverage and accuracy of the Finnish DPR is very high, only the data on reimbursed medications are available from this register. The costs of medications are reimbursed after the holder of the marketing authorisation has applied for reimbursement and demonstrated a reasonable wholesale price, which has been confirmed by the Pharmaceuticals Pricing Board . Moreover, the Pharmaceuticals Pricing Board can restrict the basis of reimbursement for a medicinal product to a precisely defined diagnosis. For example, medications for erectile dysfunction caused by diabetes are not justified for reimbursement, and therefore they do not appear in the register. Some changes due to legislative amendments have also affected the content and coverage of this register. Since 2006 the coverage of the DPR has improved. The fixed deductible rate per purchase for medications was given up and, instead, a certain percentage of the price was calculated on the basis of reimbursement category. As a consequence of this, inexpensive medications that had not reached the limit before are now recorded in the database. Moreover, since 2007 medications funded by employers have also been recorded in the register. Nevertheless, the DPR database provides an excellent resource to study medication utilisation and costs. Furthermore, since all patients in this study have been affected by the above mentioned changes in the same way, we are confident that these changes have had only a minor effect on the results.
Finally, we did not receive comprehensive information on comorbidities unrelated to diabetes or its complications, such as other autoimmune diseases or cancer. Thus, we were not able to control for these unrelated comorbidities in the multivariate model, which might have had some minor effects on the results.
In conclusion, although diabetes itself generates high medication costs, our findings highlight the high cost of renal failure; it dramatically increases the total cost of prescription medications in outpatients with type 1 diabetes. On the contrary, the cost of diabetes medication is stable irrespective of complication status and duration of diabetes. Although the incidence of ESRD has decreased, the number of patients with ESRD will continue to rise worldwide due to the growing number of individuals with diabetes. Therefore, both healthcare professionals and policymakers should be aware that all interventions to prevent or delay ESRD will save not only medication costs, but also the long-term costs of diabetes as a whole. In preventing complications, healthcare professionals should pay particular attention to motivating individuals with diabetes to conduct better self-care from the very beginning of the disease process.