This study analyzed the cost of diabetes drugs and its effect on CV events and deaths in Korea using the National Health Insurance data. From 2009 to 2018, the incidence rates of CV events and deaths were 28.1% and 8.4%, respectively. CV events were higher in older adults, men, rural dwellers, those with the lowest and highest income, and those with hypertension. According to the cost quartiles, the risk of CV events increased in sequential order and CV deaths showed a U-shaped pattern, with Q3 being the lowest. In addition, men, aging, types of diabetes drugs used, presence of hypertension, and smoking status were attributed to CV risks.
The incidence of CV events and deaths has been decreasing over the past two decades [11–13]. However, the healthcare expenditure for CV disease is higher (12–16.5%) than that for other diseases (0.2–0.4%) [14]. The primary prevention of CV disease is important to reduce the diabetes-related financial burden [15, 16]. Globally, the indirect diabetes cost (caused by production losses due to premature mortality and morbidity) accounted for 34.7% of the total expenditures, suggesting that increasing the amount spent on paying the direct diabetes cost (diabetes prevention and treatment) might reduce the total economic burden of diabetes [4].
In Q1, the annual incidence of CV events was the highest in the first year but was lowest in the seventh year and thereafter. After adjustments, the risk of CV events was lowest. It is presumed that over time, the proportion of individuals who only took a few diabetic drugs with good glucose control increased in this group. By contrast, Q4 showed the highest 10-year incidence of CV events. The high expenditure on insulin and SU is likely to suggest that there were many patients with advanced stage of diabetes in this group. After adjustments, the risk of CV events and death was the highest. The highest expenditure reflects poor blood glucose control, and appropriate management is required for clinical intervention, patient self-management education, and social support for diabetes patients [8].
In Q3, the 10-year incidence of CV events and death was the lowest. After adjustment, the risk of CV events was lower than Q4 but higher than Q1, while that of CV death was the lowest. The most expensive diabetes drug was GLP-1RA (80 USD/year per prescription), whereas traditional therapies were cheap (insulin, 14 USD/year per prescription; SU, 7 USD/year per prescription; MET, 4 USD/year per prescription; data not shown). Considering that Q3 had the highest expenditure on GLP-1RA after MET+DPP4i, and Q4 had the highest expenditure on SU combination and insulin, the affordability of diabetes drugs might affect the incidence of CV events and death among individuals with similar CV risk.
This study reflects the real-world trends of diabetes drug prescription and its cost, and not a randomized control trial. Therefore, the results of the Cox regression analysis in this study showed that MET+DPP4i or MET+TZD decreased and insulin, SU, or MET increased the risk of CV events and death, and this finding should not be interpreted based on the CV benefit of the drug. Moreover, only short-term data of GLP-1RA (2016-2018) were included, mainly dulaglutide which was launched in 2016. Recently, the results of the Glycemia Reduction Approaches in Diabetes study, a comparative study on the effect of adding insulin (glargine), SU (glimepiride), GLP1-RA (liraglutide), or DPP4i (sitagliptin) to pre-existing metformin, were presented at the 2021 American Diabetes Association meeting [17]. As for the incidence of major CV events, the incidence of hospitalization for HF and all-cause mortality did not differ among the four classes of medications. However, liraglutide was associated with a lower incidence of CV events than the other three agents.
Along with lifestyle modification, appropriate prescription based on the patients’ clinical characteristics, drug efficacy, and side effects can help prevent the occurrence of diabetes complications and improve the patient’s quality of life [18, 19]. Various cost patterns exist depending on the combination of antidiabetic drugs, and treatment strategies often change because of the patient’s ability to afford the cost of treatment or medications [20]. The effective combination of diabetic drugs is more costly [1, 21], which might not be affordable for individuals living in low-and lower-middle-income countries [22, 23].
The direct medical costs for diabetes treatment is determined early, which seems to be cost-ineffective in the short term; however, many health benefits accrue late [8]. In the long run, diabetic patients without complications can save nine times of the direct medical costs compared with those with diabetes-related complications [24]. The scenario analysis using the Italian National Health Service revealed that integrated management, such as control of HbA1c, microalbuminuria, cholesterol, and blood pressure levels, can reduce the diabetes costs by 17% [25]. In addition, a 5-year prospective cohort study in Hong Kong revealed that multidisciplinary risk assessment and management of diabetes reduced the cumulative incidences of complications and all-cause mortality and had a net saving of USD 7,294 per participant [26]. Taken together, the long-term benefits can be achieved by appropriate treatment of diabetes and ensuring an adequate medical expenditure.
The main strength of this study is that it documented the impact of diabetes cost on the risk of CV events and death, a less explored area of research. In addition, this study is based on a high-quality data source, the National Health Insurance data, which is the most representative health data in Korea. Using big data, our results show the overall diabetes cost, prescription pattern, and incidence of CV events.
Despite these strengths, there are also some limitations. First, the data does not contain laboratory levels; hence, we could not evaluate the severity of diabetes and comorbidities. Second, the treatment (e.g., statin) and improvement of comorbidities within the 10-year period were not reflected; hence, the results were affected, and it was not emphasized that the presence of dyslipidemia and obesity at baseline was a protective factor for CV events and death. Third, diabetes drugs with established cardiovascular benefits (SGLT2i and GLP1-RA) were not adjusted during the performance of a Cox regression analysis as they were prescribed only after a 3–4-year follow-up. Lastly, Korea’s unique health insurance system and diabetes drug prescription trends [27], which is insufficient to reflect the global trends, should be taken into account.