Long-term effects of a sustained-release preparation of acipimox on dyslipidemia and glucose metabolism in non—insulin-dependent diabetes mellitus☆

Abstract 

Elevated circulating plasma nonesterified fatty acids (NEFA) may contribute to the insulin resistance and hyperglycemia of non—insulin-dependent diabetes mellitus (NIDDM), and decreasing plasma NEFA could provide a therapeutic benefit. A sustained-release preparation of acipimox, a lipolysis inhibitor, was used in an attempt to decrease circulating plasma NEFA levels long-term, and the effects on glycemic control, insulin resistance, and serum lipids were measured. Sixty NIDDM patients (43 males and 17 females) took part in a randomized controlled trial of acipimox or placebo for 12 weeks. Fasting plasma NEFA levels did not change in acipimox-treated patients (baseline v 12 weeks, 0.84 ± 0.35 v 0.88 ± 0.55 mmol · L⁻¹, mean ± SD). Fasting blood glucose was unchanged (mean difference v placebo, −0.5 mmol · L⁻¹; 95% confidence interval [CI], −1.4 to 0.3 mmol · L⁻¹), but serum fructosamine decreased (mean difference v placebo, −26 μmol · L⁻¹; 95% CI, −51 to 0 mmol · L⁻¹), as did the standardized hemoglobin A₁ ([HbA₁] mean difference v placebo, −1.4%; 95% CI, −3.0% to −0.1%). Insulin resistance measured as steady-state plasma glucose during an insulin-dextrose infusion test was unchanged (mean difference v placebo, −1.4 mmol · L⁻¹; 95% CI, −3.2 to 0.5 mmol · L⁻¹). Serum total cholesterol (mean difference v placebo, −0.4 mmol · L⁻¹; 95% CI, −0.6 to −0.1 mmol · L⁻¹), serum apolipoprotein B ([apo B] mean difference v placebo, −0.19 g · L⁻¹; 95% CI, −0.3 to −0.1 g · L⁻¹), and serum triglycerides (mean difference v placebo for pretreatment v posttreatment ratio, 0.59; 95% CI, 0.40 to 0.88) were all lower with acipimox. Serum high-density lipoprotein (HDL) cholesterol (mean difference v placebo, 0.10 mmol · L⁻¹; 95% CI, −0.05 to 0.3 mmol · L⁻¹), serum apo A1 (mean difference v placebo, 0.03 g · L⁻¹; 95% CI, −0.04 to 0.1 g · L⁻¹), and serum lipoprotein(a) ([Lp(a)] acipimox v placebo, 154 (0 to 1,574) v 71 (0 to 1,009), median and range) were unchanged. Despite the lack of change in fasting plasma NEFA levels, acipimox caused a modest beneficial improvement in overall glycemic control and plasma lipids in NIDDM patients and could be a useful agent in the treatment of dyslipidemic NIDDM patients.

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