Type 2 diabetes mellitus: safety and efficacy of evolocumab

Takeaway

• BANTING study demonstrated that in statin-treated patients with type 2 diabetes mellitus (T2DM) and hypercholesterolaemia or mixed dyslipidaemia, addition of evolocumab significantly reduced low-density lipoprotein-cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (non-HDL-C).
• Evolocumab led to favourable changes in post-prandial chylomicrons, very LDL-C (VLDL-C) and LDL-C levels.

Why this matters

• Several guidelines support more aggressive LDL-C lowering to levels <1.81 mmol/l in individuals with atherosclerotic cardiovascular disease or <2.6 mmol/l in individuals with diabetes.
• Findings support the efficacy and safety of evolocumab therapy in patients with T2DM and hyperlipidaemia or mixed dyslipidaemia.

Study design

• Patients with T2DM (n=421) receiving maximally tolerated statin therapy were randomly assigned 2:1 to receive 12 weeks of monthly evolocumab 420 mg (n=280) and placebo (n=141).
• Primary outcome: mean percentage change in LDL-C from baseline to 12 weeks and to the mean of 10 and 12 weeks.
• Secondary outcome: mean percentage change in non-HDL-C, other lipids parameters, LDL-C <1.81 mmol/L and LDL-C reduction ≥50% from baseline to 12 weeks and the mean of 10 and 12 weeks.
• Funding: Amgen Inc.

Key results

• At 12 and the mean of 10 and 12 weeks, evolocumab vs placebo showed a significant reduction in:
  • LDL-C level (mean difference [MD], 53.1% and 64.1%, respectively; P<.0001),
  • non-HDL-C level (MD, 46.3% and 56.6%, respectively; P<.0001).
• Evolocumab significantly improved other lipid parameters, and a higher proportion of patients in evolocumab vs placebo group achieved LDL-C <1.81 mmol/L and ≥50% reduction in LDL-C levels (P<.0001 for all).
• Evolocumab showed favourable changes in chylomicron triacylglycerol and cholesterol, VLDL-C and LDL-C level after mixed-meal tolerance test vs placebo group (P<.05).
• Evolocumab did not show any significant effects on glycaemic parameters and was safe and well tolerated.

Limitations

• Short-follow-up.