Early combination lipid-lowering therapy in patients with diabetic dyslipidemia

Patients with type 2 diabetes mellitus and established cardiovascular disease are classified as being at very high cardiovascular risk, requiring achievement of low-density lipoprotein cholesterol (LDL-C) target levels of <1.4 mmol/L according to the recommendations of the European Society of Cardiology. Statin monotherapy is often insufficient to achieve recommended lipid targets, supporting the rationale for early combination lipid-lowering therapy. The aim of this study was to evaluate the efficacy and safety of early combination therapy with rosuvastatin plus ezetimibe compared with rosuvastatin monotherapy in patients with diabetic dyslipidemia and very high cardiovascular risk. A prospective randomized study included 50 patients divided into two groups of 25 participants each: rosuvastatin 20 mg/day and rosuvastatin 20 mg combined with ezetimibe 10 mg/day. The follow-up period was 12 weeks. Baseline characteristics were comparable between groups: mean age was 58.2 ± 6.4 and 57.6 ± 7.1 years, male proportion was 56% and 52%, body mass index was 30.1 ± 3.2 and 29.8 ± 3.5 kg/m², HbA1c levels were 7.8 ± 0.9% and 7.7 ± 1.0%, LDL-C levels were 3.2 ± 0.6 and 3.3 ± 0.5 mmol/L, ApoB levels were 1.12 ± 0.18 and 1.15 ± 0.16 g/L, and Lp(a) concentrations were 32 ± 14 and 34 ± 16 mg/dL, respectively (p>0.05 for all comparisons). After 12 weeks, LDL-C reduction was 43.9% (95% CI: 39.2–48.6) in the monotherapy group and 57.8% (95% CI: 53.1–62.5) in the combination therapy group (p<0.001). LDL-C target levels of <1.4 mmol/L were achieved in 44% and 72% of patients, respectively (p=0.03). ApoB reduction was significantly greater in the combination therapy group: 27.4% (95% CI: 23.0–31.8) versus 36.2% (95% CI: 32.1–40.3) (p=0.002). The ApoB/ApoA1 ratio decreased by 38.1% and 42.3%, respectively (p=0.04), while ApoA1 changes were not statistically significant. No significant differences in Lp(a) dynamics were observed between the groups (p=0.56). The incidence of adverse events was comparable, including myalgia (8% vs. 6%) and elevated transaminases (4% in both groups), and no treatment discontinuation was required. Early combination therapy provides a more pronounced reduction in atherogenic lipids and a higher rate of LDL-C target achievement compared with rosuvastatin monotherapy in patients with diabetic dyslipidemia and very high cardiovascular risk. The absence of significant effects on Lp(a) suggests persistence of residual cardiovascular risk and highlights the need for further therapeutic optimization.