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

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. Easting 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). Easting 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 mu mol.L-1; 95% CI, -51 to 0 mmol.L-1), as did the standardized hemoglobin A(1) ([HbA(1)] 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 Al (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. Copyright (C) 1998 by W.B. Saunders Company.