Recent publications on Residual Risk

Volanesorsen, a second generation antisense inhibitor of apolipoprotein (apo) CIII, substantially reduced plasma apoC-III and triglycerides in type 2 diabetes patients with elevated triglycerides (>200 and <500 mg/dL). Treatment was also associated with marked improvement in insulin sensitivity. This randomized, double-blind, placebo-controlled trial enrolled 15 type 2 diabetes patients (mean age 56.5 years, 73% women, mean HbA1c 7.9%, baseline triglycerides 249 mg/dL). Patients were allocated to treatment with volanesorsen 300 mg or placebo administered subcutaneously on days 1, 3, 5, 8, 15, 22, 29, 35, 42, 49, 56, 63, 70, 78, and 85 (15 doses). Insulin sensitivity was assessed using a two-step hyperinsulinaemic-euglycaemic clamp procedure, before and after study treatment. Eleven of the 15 patients received all 15 doses. Compared with placebo, treatment with volanesorsen resulted in significant reductions in apoCIII by 88% and triglycerides by 69% (p<0.05), and also increased high-density lipoprotein cholesterol by 42% (p<0.05). Intriguingly, there was also significant improvement in whole-body insulin sensitivity (by 57%, p<0.001), in relation to changes in both apoCIII and triglycerides (p=0.03 and p=0.01, respectively). On the strength of these findings, albeit in a small sample of patients treated for a short duration, further investigation of the efficacy of volanesorsen to better define those patients most likely to benefit from treatment is merited.