Rosuvastatin Monotherapy Versus Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity, Vascular Inflammation, and Lipid Profile In Patients With Type 2 Diabetes Mellitus: A Randomised Controlled Trial

Abstract

Background: Type 2 diabetes mellitus (T2DM) is characterised by insulin resistance, atherogenic dyslipidaemia, and chronic low-grade inflammation, collectively elevating atherosclerotic cardiovascular disease (ASCVD) risk. Statins are the cornerstone of lipid-lowering therapy in T2DM; however, the potential of rosuvastatin/ezetimibe combination therapy to provide additional cardiometabolic benefits beyond lipid lowering remains incompletely characterised.

Methods: A prospective, open-label, parallel-group randomised controlled trial was conducted at a tertiary care centre in Tamil Nadu, India. Ninety statin-naive adults with T2DM and dyslipidaemia were randomised 1:1 to rosuvastatin 10 mg monotherapy (Group I) or rosuvastatin 5 mg plus ezetimibe 10 mg combination therapy (Group II) once daily for 12 weeks. Primary outcomes were changes in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein (hsCRP), and LDL cholesterol from baseline to week 12. Secondary outcomes included changes in fasting insulin, HDL cholesterol, triglycerides, fasting blood sugar (FBS), and glycated haemoglobin (HbA1c).

Results: Both groups were comparable at baseline. Combination therapy produced significantly greater reductions in LDL cholesterol (mean change: −27.2 mg/dL vs −19.2 mg/dL; p = 0.02), HOMA-IR (−1.01 vs −0.49; p = 0.002), and hsCRP (−0.41 mg/L vs −0.20 mg/L; p = 0.01) compared with monotherapy. HDL cholesterol increased more in Group II (45.6 ± 6.8 vs 43.5 ± 6.4 mg/dL; p = 0.03), and triglyceride reduction was also greater (p = 0.04). Fasting insulin declined significantly in Group II (p = 0.03). Although both groups demonstrated significant within-group reductions in FBS and HbA1c, the intergroup difference in HbA1c was not statistically significant (p = 0.21).

Conclusions: Rosuvastatin/ezetimibe combination therapy demonstrated superior efficacy over rosuvastatin monotherapy in improving lipid parameters, reducing insulin resistance, and attenuating systemic inflammation in patients with T2DM and dyslipidaemia. hese findings suggest that rosuvastatin/ezetimibe combination therapy may offer additional cardiometabolic benefits compared with rosuvastatin monotherapy in patients with T2DM and dyslipidaemia.