Lipid-lowering therapy and LDL target attainment in type 2 diabetes: trends from the Italian Associations of Medical Diabetologists database

Abstract

Background: Hypercholesterolemia is a major cardiovascular risk factor, particularly in individuals with type 2 diabetes (T2DM), where cardiovascular events are more prevalent. Adherence to low-density lipoprotein cholesterol (LDL-c) targets remains suboptimal globally and in Italy. This study evaluates trends in LDL-c target achievement and lipid-lowering treatment with a stratification by cardiovascular risk among Italian patients with type 2 diabetes from 2019 to 2022.

Methods: A cross-sectional analysis was conducted using the AMD Annals database, encompassing over 700,000 patients with T2DM. Patients were categorized by cardiovascular risk levels, LDL-c ranges and therapy types (statins, ezetimibe, PCSK9 inhibitors). Linear trends across the four years were evaluated.

Results: The percentage of patients achieving LDL-c targets improved across all risk levels. In very high-risk patients, LDL-c < 55 mg/dL was achieved by 16.3% in 2019, increasing to 23.6% in 2022. High-risk patients achieving LDL-c < 70 mg/dL rose from 20.3 to 26.6% over the same period. Use of PCSK9 inhibitors, particularly in combination with statins, was associated with the highest target achievement rates, reaching 62% in very high-risk patients by 2022. We observed a reduction of moderate-intensity statins use in favor of combination therapies across the four years. Despite this, nearly one-third of patients still had LDL-c levels ≥ 100 mg/dL in 2022.

Conclusions: While LDL-c management in Italian patients with T2DM has improved, significant gaps remain, particularly for very high-risk individuals. Expanding the use of advanced therapies like PCSK9 inhibitors and adhering more closely to guideline-based recommendations are critical to improve cardiovascular risk in this population.

Keywords: Cardiovascular risk; Hypercholesterolemia; LDL cholesterol; Lipid-lowering therapy; PCSK9 inhibitors; Statins; Type 2 diabetes mellitus.

Fig. 1

Flowchart of patient selection process

Fig. 2

Trends in lipid profiles (2019–2022). For all three variables—LDL, HDL, and triglycerides—the p-value for the trend over the 4-year period is < 0.01

Fig. 3

Yearly distribution of patients with T2DM by cardiovascular risk level and treatment coverage. Trends were calculated for the change, between 2019 and 2022, within the three risk subgroups. The p-value for trend is < 0.01

Fig. 4

Proportion of patients achieving LDL-c targets by risk level. The p-value for trend related each year during the 2019–2022 period is < 0.01 for all three risk levels

Fig. 5

Distribution over the years of patients with type 2 diabetes and CAD (target < 55 mg/dl), by LDL-C range. Percentages of patients in each LDL-C range for each year of the 2019–2022 period is significantly different, p < 0.01

Fig. 6

Distribution over the years of patients with type 2 diabetes and organ damage (including one or more between CKD, CAD, heart failure, cerebrovascular disease; target < 55 mg/dl) by LDL-C range. Percentages of patients in each LDL-C range for each year of the 2019–2022 period is significantly different, p < 0.01